Direct and continuous generation of pure acetic acid solutions via electrocatalytic carbon monoxide reduction

Electrochemical CO₂ or CO reduction to high-value C₂₊ liquid fuels is desirable, but its practical application is challenged by impurities from cogenerated liquid products and solutes in liquid electrolytes, which necessitates cost- and energy-intensive downstream separation processes. By coupling rational designs in a Cu catalyst and porous solid electrolyte (PSE) reactor, here we demonstrate a direct and continuous generation of pure acetic acid solutions via electrochemical CO reduction. With optimized edge-to-surface ratio, the Cu nanocube catalyst presents an unprecedented acetate performance in neutral pH with other liquid products greatly suppressed, delivering a maximal acetate Faradaic efficiency of 43%, partial current of 200 mA⋅cm⁻², ultrahigh relative purity of up to 98 wt%, and excellent stability of over 150 h continuous operation. Density functional theory simulations reveal the role of stepped sites along the cube edge in promoting the acetate pathway. Additionally, a PSE layer, other than a conventional liquid electrolyte, was designed to separate cathode and anode for efficient ion conductions, while not introducing any impurity ions into generated liquid fuels. Pure acetic acid solutions, with concentrations up to 2 wt% (0.33 M), can be continuously produced by employing the acetate-selective Cu catalyst in our PSE reactor.

Electrochemically reducing carbon dioxide (CO₂) or carbon monoxide (CO) to commodity fuels or chemicals, with the input of green and economical renewable electricity, has become an alternative route to traditional chemical engineering processes (1–7). To date, a variety of catalysts have been demonstrated to reduce CO₂ into C₁ products (CO, formate, etc.) with high Faradaic efficiencies (FEs) (6, 8–14); however, the critical step of C-C coupling toward high-value C₂₊ products was rarely observed on catalysts other than Cu (15–20). Due to its proper binding strength with *CO (19, 21, 22), Cu has shown the capability of catalyzing the coupling of two carbons or more in CO₂/CO reduction reactions (CO₂RR/CORR), which, however, typically suffers from large overpotential and low selectivity (23–25). In previous studies on Cu catalysts, tremendous efforts have been focused on how to promote C-C coupling toward high selectivity of C₂₊ products, including facet engineering (26–28), grain boundary engineering (29, 30), surface modifications (31–33), etc. For example, recent studies on facet dependence of C-C coupling have shown that the C₂₊ selectivity could be improved on Cu(100) compared to other facets due to more stabilized *OCCO intermediates (26, 34). While the overall C₂₊ selectivity is constantly improved by researchers in this field, the generated products are typically a mixture of different C₂₊ compounds, which subsequently necessitates energy- and cost-intensive downstream product separation and purification processes (35–37). A solution to continuously obtain a highly pure, single C₂₊ product stream, which can be directly fed into practical applications, will impose a significant scientific and economic impact but has been rarely studied before.Ethylene, ethanol, and acetate are the three major C₂ products that have been widely reported in CO₂RR/CORR on Cu materials (16–18, 38–44). Compared to gas-phase products, liquid products show significant advantages due to their high energy densities and ease of storage and distribution (45). Nevertheless, the generation of a high-purity C₂ liquid fuel via electrochemical CO₂RR/CORR is challenging due to the involvement of two types of impurities. First, in previous studies of Cu catalysts, while the C₂ product can be dramatically increased by strategies such as exposing (100) facets, ethanol and acetic acid usually share the same potential window and are cogenerated simultaneously, making it difficult to obtain a single C₂ liquid product (29, 46, 47); Second, in traditional H-cell or flow-cell reactors, the generated liquid products were mixed with solutes in liquid electrolytes such as KOH or KHCO₃, which requires extra separation and concentration processes to recover pure liquid fuel solutions in practical applications (37, 48, 49). An integration of rational design in both catalytic material and reactor, for high single-C₂ selectivity and electrolyte-free liquid fuel output, respectively, therefore becomes the key to achieve the goal of pure C₂ liquid fuels.Here we report the continuous generation of pure acetic acid solutions via CORR on Cu nanocube (NC) catalysts in a porous solid electrolyte (PSE) reactor. By flexibly tuning the edge to (100) surface ratio, the medium-size Cu NC catalyst exhibits a maximal acetate Faradaic efficiency of 43% with a partial current density of ∼200 mA⋅cm⁻² in neutral pH, setting up a different acetate performance benchmark (18, 40, 41). More importantly, the selectivity of other liquid products (ethanol and trace amount of n-propanol) was suppressed to below 2%, suggesting an ultrahigh acetic acid relative purity of up to 98 wt%. An impressive stability was demonstrated by a continuous operation of CORR under 150 mA⋅cm⁻² current for over 150 h with negligible degradation in selectivity and activity. This acetate-selective Cu NC catalyst was successfully employed into our PSE reactor for the continuous generation of electrolyte-free, pure acetic acid solutions, with overall current of up to 1 A⋅cm⁻² and acetic acid relative purity as high as 96 wt%. Different from the traditional liquid electrolyte, our PSE layer can efficiently conduct ions while it does not introduce any impurity ions into the generated liquid products. Density functional theory (DFT) calculations suggest that the stepped edge sites on the Cu NC readily dissociate *OCCOH into *CCO and *OH, which is a key step in promoting the formation of acetate. We propose that the large NC has a low edge-to-facet ratio and therefore cogenerates considerable ethanol and ethylene instead of acetate, while a small NC provides less active (100) area for C-C coupling and therefore predominantly catalyzes the hydrogen evolution reaction (HER) instead of yielding C₂ products.     

In situ organic Fenton-like catalysis triggered by anodic polymeric intermediates for electrochemical water purification

Organic Fenton-like catalysis has been recently developed for water purification, but redox-active compounds have to be ex situ added as oxidant activators, causing secondary pollution problem. Electrochemical oxidation is widely used for pollutant degradation, but suffers from severe electrode fouling caused by high-resistance polymeric intermediates. Herein, we develop an in situ organic Fenton-like catalysis by using the redox-active polymeric intermediates, e.g., benzoquinone, hydroquinone, and quinhydrone, generated in electrochemical pollutant oxidation as H₂O₂ activators. By taking phenol as a target pollutant, we demonstrate that the in situ organic Fenton-like catalysis not only improves pollutant degradation, but also refreshes working electrode with a better catalytic stability. Both ¹O₂ nonradical and ·OH radical are generated in the anodic phenol conversion in the in situ organic Fenton-like catalysis. Our findings might provide a new opportunity to develop a simple, efficient, and cost-effective strategy for electrochemical water purification.

The efficient generation of reactive oxygen species is essential for pollutant degradation in water purification. The metal-mediated Fenton catalysis has been widely used for several decades owning to its high efficiency, low cost, and easy operation (1). However, it has several technical drawbacks to largely limit further applications, e.g., harsh pH, metal-rich sludge, secondary pollution, and poor stability (1). Alternatively, the metal-free Fenton catalysis has recently attracted increasing interests. Redox-active compounds serve as the oxidant activator to decompose pollutants via radical and/or nonradical pathways (2–5). These pathways depend highly on the atomic and electronic structures and molecular configurations of compounds and their molecular interactions with oxidants (6–18). So far organic activators are ex situ introduced and cause secondary pollution, although the performance can be largely improved (2–18). Such an intrinsic drawback greatly restricts its practical applications. Thus, in situ organic Fenton-like catalysis without secondary pollution is greatly desired for clean and safe water purification.Electrochemical oxidation (EO) at low bias is widely used for pollutant degradation owning to its high current efficiency and low energy consumption, but largely suffers from electrode fouling (19, 20). Such fouling is mainly caused by anodic polymeric intermediates with large molecular size, low geometric polarity, and high structural stability, thus anodic oxidation is thermodynamically terminated at this stage (19, 20). How to remove polymeric intermediates is essential for electrochemical water purification. It is interesting to note that anodic polymeric intermediates usually contain quinonelike moieties (C = O) and persistent organic radicals, as the electrons in nucleophilic C-OH can be readily transferred to generate C-O· and C = O (19, 20). Quinonelike moieties are redox-active because of their high electron density and strong electron-donating properties, thus can serve as the metal ligand and reductant to enhance transition-metal redox cycling, and also be involved in the environmental geochemistry of natural organic matters (21–30). Moreover, quinonelike moieties and persistent organic radicals can directly serve as an organic activator to initiate organic Fenton-like catalysis for environmental remediation (31–40). Thus, these redox-active anodic polymeric intermediates are likely to trigger organic Fenton-like catalysis.Inspired by above analyses, we constructed and validated in situ organic Fenton-like catalysis for electrochemical water purification at low bias before oxygen evolution (Scheme 1). Phenol, a model chemical widely present in environments, and other typical halogenated and nonhalogenated aromatic compounds were selected as target pollutants. Carbon felt (CF), a model material with high activity and low cost, and other typical dimensionally stable anodes were selected as target electrodes. Reaction systems were named in the form of “EO + ex situ added reagent + cathode,” as their anodes were identical. Pollutant degradation and electrode antifouling performances were evaluated under various conditions. After the major reactive oxygen species were identified using a suite of testing methods, and the potential role of trace transition metals, especially iron and copper, was examined, the possible molecular mechanism of the in situ organic Fenton-like catalysis was proposed.Open in a separate windowScheme 1.Scheme diagrams of the EO-Ti, EO/H₂O₂-Ti, and EO/O₂-CF systems.     

Tropospheric carbonyl sulfide mass balance based on direct measurements of sulfur isotopes

Robust estimates for the rates and trends in terrestrial gross primary production (GPP; plant CO₂ uptake) are needed. Carbonyl sulfide (COS) is the major long-lived sulfur-bearing gas in the atmosphere and a promising proxy for GPP. Large uncertainties in estimating the relative magnitude of the COS sources and sinks limit this approach. Sulfur isotope measurements (³⁴S/³²S; δ³⁴S) have been suggested as a useful tool to constrain COS sources. Yet such measurements are currently scarce for the atmosphere and absent for the marine source and the plant sink, which are two main fluxes. Here we present sulfur isotopes measurements of marine and atmospheric COS, and of plant-uptake fractionation experiments. These measurements resulted in a complete data-based tropospheric COS isotopic mass balance, which allows improved partition of the sources. We found an isotopic (δ³⁴S ± SE) value of 13.9 ± 0.1‰ for the troposphere, with an isotopic seasonal cycle driven by plant uptake. This seasonality agrees with a fractionation of −1.9 ± 0.3‰ which we measured in plant-chamber experiments. Air samples with strong anthropogenic influence indicated an anthropogenic COS isotopic value of 8 ± 1‰. Samples of seawater-equilibrated-air indicate that the marine COS source has an isotopic value of 14.7 ± 1‰. Using our data-based mass balance, we constrained the relative contribution of the two main tropospheric COS sources resulting in 40 ± 17% for the anthropogenic source and 60 ± 20% for the oceanic source. This constraint is important for a better understanding of the global COS budget and its improved use for GPP determination.

The Earth system is going through rapid changes as the climate warms and CO₂ level rises. This rise in CO₂ is mitigated by plant uptake; hence, it is important to estimate global and regional photosynthesis rates and trends (1). Yet, robust tools for investigating these processes at a large scale are scarce (2). Recent studies suggest that carbonyl sulfide (COS) could provide an improved constraint on terrestrial photosynthesis (gross primary production, GPP) (2–12). COS is the major long-lived sulfur-bearing gas in the atmosphere and the main supplier of sulfur to the stratospheric sulfate aerosol layer (13), which exerts a cooling effect on the Earth’s surface and regulates stratospheric ozone chemistry (14).During terrestrial photosynthesis, COS diffuses into leaf stomata and is consumed by photosynthetic enzymes in a similar manner to CO₂ (3–5). Contrary to CO₂, COS undergoes rapid and irreversible hydrolysis mainly by the enzyme carbonic-anhydrase (6, 7). Thus, COS can be used as a proxy for the one-way flux of CO₂ removal from the atmosphere by terrestrial photosynthesis (2, 8–11). However, the large uncertainties in estimating the COS sources weaken this approach (10–12, 15). Tropospheric COS has two main sources: the oceans and anthropogenic emissions, and one main sink–terrestrial plant uptake (8, 10–13). Smaller sources include biomass burning, soil emissions, wetlands, volcanoes, and smaller sinks include OH destruction, stratospheric destruction, and soil uptake (12). The largest source of COS to the atmosphere is the ocean, both as direct COS emission, and as indirect carbon disulfide (CS₂) and dimethylsulfide (DMS) emissions that are rapidly oxidized to COS (10, 16–20). Recent studies suggest oceanic COS emissions are in the range of 200–4,000 GgS/y (19–22). The second major COS source is the anthropogenic source, which is dominated by indirect emissions derived from CS₂ oxidation, mainly from the use of CS₂ as an industrial solvent. Direct emissions of COS are mainly derived from coal and fuel combustion (17, 23, 24). Recent studies suggest that anthropogenic emissions are in the range of 150–585 GgS/y (23, 24). The terrestrial plant uptake is estimated to be in the range of 400–1,360 GgS/y (11). Measurements of sulfur isotope ratios (δ³⁴S) in COS may be used to track COS sources and thus reduce the uncertainties in their flux estimations (15, 25–27). However, the isotopic mass balance approach works best if the COS end members are directly measured and have a significantly different isotopic signature. Previous δ³⁴S measurements of atmospheric COS are scarce and there have been no direct measurements of two important components: the δ³⁴S of oceanic COS emissions, and the isotopic fractionation of COS during plant uptake (15, 25–27). In contrast to previous studies that used assessments for these isotopic values, our aim was to directly measure the isotopic values of these missing components, and to determine the tropospheric COS δ³⁴S variability over space and time.     

Ammonium transporter expression in sperm of the disease vector Aedes aegypti mosquito influences male fertility

The ammonium transporter (AMT)/methylammonium permease (MEP)/Rhesus glycoprotein (Rh) family of ammonia (NH₃/NH₄⁺) transporters has been identified in organisms from all domains of life. In animals, fundamental roles for AMT and Rh proteins in the specific transport of ammonia across biological membranes to mitigate ammonia toxicity and aid in osmoregulation, acid–base balance, and excretion have been well documented. Here, we observed enriched Amt (AeAmt1) mRNA levels within reproductive organs of the arboviral vector mosquito, Aedes aegypti, prompting us to explore the role of AMTs in reproduction. We show that AeAmt1 is localized to sperm flagella during all stages of spermiogenesis and spermatogenesis in male testes. AeAmt1 expression in sperm flagella persists in spermatozoa that navigate the female reproductive tract following insemination and are stored within the spermathecae, as well as throughout sperm migration along the spermathecal ducts during ovulation to fertilize the descending egg. We demonstrate that RNA interference (RNAi)-mediated AeAmt1 protein knockdown leads to significant reductions (∼40%) of spermatozoa stored in seminal vesicles of males, resulting in decreased egg viability when these males inseminate nonmated females. We suggest that AeAmt1 function in spermatozoa is to protect against ammonia toxicity based on our observations of high NH₄⁺ levels in the densely packed spermathecae of mated females. The presence of AMT proteins, in addition to Rh proteins, across insect taxa may indicate a conserved function for AMTs in sperm viability and reproduction in general.

Ammonium transporters (AMTs), methylammonium permeases (MEPs), and Rhesus glycoproteins (Rh proteins) comprise a protein family with three clades, and homologs from each have been identified in virtually all domains of life (1). AMT proteins were first identified in plants (2) with the simultaneous discovery of MEP proteins in fungi (3), followed by Rh proteins in humans (4). Ammonia (NH₃/NH₄⁺) is vital for growth in plants and microorganisms and is retained in some animals for use as an osmolyte (5, 6), for buoyancy (7, 8), and for those lacking sufficient dietary nitrogen (9). In the majority of animals, however, ammonia is the toxic by-product of amino acid and nucleic acid metabolism and, accordingly, requires efficient mechanisms for its regulation, transport, and excretion (10–13). AMT, MEP, and Rh proteins are responsible for the selective movement of ammonia (NH₃) or ammonium (NH₄⁺) across biological membranes, a process that all organisms require. Unlike their vertebrate, bacterial, and fungal counterparts which function as putative NH₃ gas channels (14–18), a myriad of evidence suggests that plant AMT proteins and closely related members in some animals are functionally distinct and facilitate electrogenic ammonium (NH₄⁺) transport (17, 19–22). In contrast to vertebrates which only possess Rh proteins (23), many invertebrates are unique in that they express both AMT and Rh proteins, sometimes in the same cell (24–28). Among insects, the presence of both AMT and Rh proteins has been described in Drosophila melanogaster (29, 30) and mosquitoes that vector disease-causing pathogens, Anopheles gambiae (22, 31) and Aedes aegypti (32, 33). It is unclear whether, in these instances, AMT and Rh proteins can functionally substitute for one another, but in the anal papillae of A. aegypti larvae, knockdown of either Amt or Rh proteins causes decreases in ammonia transport, suggesting that they do not (32–34). To date, studies on ammonia transporter (AMT and Rh) function in insects have focused on ammonia sensing and tasting in sensory structures (22, 30, 31, 35), ammonia detoxification and acid–base balance in muscle, digestive, and excretory organs (15, 36), and ammonia excretion in a variety of organs involved in ion and water homeostasis (9, 24, 32–34).A. aegypti is the primary vector for the transmission of the human arboviral diseases Zika, yellow fever, chikungunya, and dengue virus, which are of global health concern due to rapid increases in the geographical distribution of this species, presently at its highest ever (37, 38). In light of the well-documented evolution of insecticide resistance in mosquitoes (39–42), more recent methods to control disease transmission such as the sterile insect technique (43), transinfection and sterilization of mosquitoes with the bacterium Wolbachia (44), and targeted genome editing rendering adult males sterile (45) have proven effective. These methods take advantage of various aspects of mosquito reproductive biology; however, an understanding of male reproductive biology and the male contributions to female reproductive processes is still in its infancy (46). Here, we describe the expression of an A. aegypti ammonium transporter (AeAmt1) in the sperm during all stages of spermatogenesis, spermiogenesis, and egg fertilization, which is critical for fertility.     

A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior

NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical, and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in vitro excitatory actions of γ-aminobutyric acid (GABA) and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics, and behavioral performance are subtle. Our data reveal a neural network function of NKCC1 in hippocampal glutamatergic neurons in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.

Intracellular chloride concentration ([Cl⁻]_i) is a major determinant of neuronal excitability, as synaptic inhibition is primarily mediated by chloride-permeable receptors (1). In the mature brain, [Cl⁻]_i is maintained at low levels by chloride extrusion, which renders γ-aminobutyric acid (GABA) hyperpolarizing (2) and counteracts activity-dependent chloride loads (3). GABAergic inhibition in the adult is crucial not only for preventing runaway excitation of glutamatergic cells (4) but also for entraining neuronal assemblies into oscillations underlying cognitive processing (5). However, the capacity of chloride extrusion is low during early brain development (6, 7). Additionally, immature neurons are equipped with chloride uptake mechanisms, particularly with the Na⁺/K⁺/2Cl⁻ cotransporter NKCC1 (8–12). NKCC1 contributes to the maintenance of high [Cl⁻]_i in the developing brain (13), favoring depolarization through GABA_A receptor (GABA_AR) activation in vivo (14, 15).When GABA acts as a depolarizing neurotransmitter, neural circuits generate burst-like spontaneous activity (16–20), which is crucial for their developmental refinement (21–24). In vitro evidence indicates that GABAergic interneurons promote neuronal synchrony in an NKCC1-dependent manner (10, 12, 25–28). However, the in vivo developmental functions of NKCC1 are far from understood (29, 30). One fundamental question is to what extent NKCC1 and GABAergic depolarization supports correlated spontaneous activity in the neonatal brain. In the neocortex, GABA imposes spatiotemporal inhibition on network activity already in the neonatal period (14, 25, 31, 32). Whether a similar situation applies to other brain regions is unknown, as two recent chemo- and optogenetic studies in the hippocampus yielded opposing results (25, 33). Manipulations of the chloride driving force are potentially suited to resolve these divergent findings, but pharmacological (34–36) or conventional knockout (10, 11, 37) strategies suffer from unspecific effects that complicate interpretations.Here, we overcome this limitation by selectively deleting Slc12a2 (encoding NKCC1) from telencephalic glutamatergic neurons. We show that chloride uptake via NKCC1 promotes synchronized activity in acute hippocampal slices, but has weak and event type-dependent effects in CA1 in vivo. Long-term loss of NKCC1 leads to subtle changes of network dynamics in the adult, leaving synaptic development unperturbed and behavioral performance intact. Our data suggest that NKCC1-dependent chloride uptake is largely dispensable for several key aspects of hippocampal development in vivo.     

Surface plasmon mediates the visible light–responsive lithium–oxygen battery with Au nanoparticles on defective carbon nitride

Aprotic lithium-oxygen (Li-O₂) batteries have gained extensive interest in the past decade, but are plagued by slow reaction kinetics and induced large-voltage hysteresis. Herein, we use a plasmonic heterojunction of Au nanoparticle (NP)–decorated C₃N₄ with nitrogen vacancies (Au/N_V-C₃N₄) as a bifunctional catalyst to promote oxygen cathode reactions of the visible light–responsive Li-O₂ battery. The nitrogen vacancies on N_V-C₃N₄ can adsorb and activate O₂ molecules, which are subsequently converted to Li₂O₂ as the discharge product by photogenerated hot electrons from plasmonic Au NPs. While charging, the holes on Au NPs drive the reverse decomposition of Li₂O₂ with a reduced applied voltage. The discharge voltage of the Li-O₂ battery with Au/N_V-C₃N₄ is significantly raised to 3.16 V under illumination, exceeding its equilibrium voltage, and the decreased charge voltage of 3.26 V has good rate capability and cycle stability. This is ascribed to the plasmonic hot electrons on Au NPs pumped from the conduction bands of N_V-C₃N₄ and the prolonged carrier life span of Au/N_V-C₃N₄. This work highlights the vital role of plasmonic enhancement and sheds light on the design of semiconductors for visible light–mediated Li-O₂ batteries and beyond.

The aprotic lithium-oxygen (Li-O₂) battery promises ultrahigh theoretical energy density (∼3,600 Wh·kg⁻¹) and is operated with oxygen reduction to generate the product of Li₂O₂ and its reverse oxidation (2Li⁺ + O₂ + 2e⁻ ↔ Li₂O₂, E⁰ = 2.96 V) (1–5). The sluggish oxygen cathode reactions, including the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR), lead to a high discharge/charge overvoltage (∼1.0 V) during cycles and low round-trip efficiency (6–9). Since the pioneering work on the photoinvolved Li-O₂ battery using TiO₂ (10) or C₃N₄ (11) under ultraviolet (UV)-light irradiation, reduction of the charge/discharge overvoltage via a photomediated strategy has been extensively studied and is anticipated to solve the kinetic issues of the Li-O₂ battery (12–18). However, the light absorption of most semiconductors used is confined in the region of UV light, accounting for only ca. 4% of the solar spectrum (14–16). Expanding the light harvesting from UV to visible light is the long-term goal and challenge of photocatalysis (17–20). Simultaneously, high carrier recombination consumes the majority of photoelectrons and holes before catalyzing the targeted reactions, resulting in a mismatch between the carrier lifetime and kinetics of ORR or OER (19–21). This necessitates a structural design of semiconducting materials for visible-light harvesting to accelerate the cathode reactions in Li-O₂ batteries.Localized surface plasmon resonance (LSPR), which refers to the collective oscillation of conduction band (CB) electrons in metal nanocrystals under resonant excitation, has recently gained much attention (22–25). The decay of excited LSPR can produce hot electrons and holes, which initiate various chemical reactions (22, 23). Intriguingly, when plasmonic metal (e.g., Au, Ag) nanoparticles (NPs) come into contact with a semiconductor such as MoS₂, TiO₂, etc., an interfacial Schottky barrier forms; this barrier functions as a filter to force the energetic electrons or holes to migrate across the interface while inhibiting their reverse movement, thereby leading to effective electron–hole separation and suppressed charge–carrier recombination (26–30). LSPR systems generally are composed of plasmonic metal and semiconductors and exhibit the benefits of a low electron–hole recombination rate, enhanced light harvesting, and tailored response wavelengths from the visible to the near-infrared region (22). Recently, Au/CdSe (31) and Au/Ni(OH)₂ (32) heterojunctions have been attempted for a photocatalytic hydrogen evolution reaction and OER with the aid of hot electrons and holes under visible light. Coupling the plasmonic metal with suitable semiconductors for broadened light harvesting and a plasmon-enhanced effect is highly desirable for both ORR and OER in the Li-O₂ battery.Herein, we report defective C₃N₄ (Au/N_V-C₃N₄) decorated with plasmonic Au NPs as a bifunctional heterojunction catalyst that promotes cathode reactions of the Li-O₂ battery under visible light. The N_V on N_V-C₃N₄ is prone to adsorb and activate O₂, and the plasmon-excited electrons on Au migrate to the CB of N_V-C₃N₄ and relax to the N_V-induced defect band (DB) for O₂ reduction to LiO₂; then it undergoes electron reduction to Li₂O₂. Reversely, the Li₂O₂ is removed by the holes on the Au NPs driven by the applied voltage. The discharge voltage is raised to 3.16 V, and the charge voltage is lowered to 3.26 V at 0.05 mA·cm⁻² with a good rate capability and cycle stability. This investigation integrates a plasmonic heterojunction into the aprotic Li-O₂ battery and illustrates photoenergy conversion and storage under visible light.     

Coal fly ash is a major carbon flux in the Chang Jiang (Yangtze River) basin

Fly ash—the residuum of coal burning—contains a considerable amount of fossilized particulate organic carbon (FOC_ash) that remains after high-temperature combustion. Fly ash leaks into natural environments and participates in the contemporary carbon cycle, but its reactivity and flux remained poorly understood. We characterized FOC_ash in the Chang Jiang (Yangtze River) basin, China, and quantified the riverine FOC_ash fluxes. Using Raman spectral analysis, ramped pyrolysis oxidation, and chemical oxidation, we found that FOC_ash is highly recalcitrant and unreactive, whereas shale-derived FOC (FOC_rock) was much more labile and easily oxidized. By combining mass balance calculations and other estimates of fly ash input to rivers, we estimated that the flux of FOC_ash carried by the Chang Jiang was 0.21 to 0.42 Mt C⋅y⁻¹ in 2007 to 2008—an amount equivalent to 37 to 72% of the total riverine FOC export. We attributed such high flux to the combination of increasing coal combustion that enhances FOC_ash production and the massive construction of dams in the basin that reduces the flux of FOC_rock eroded from upstream mountainous areas. Using global ash data, a first-order estimate suggests that FOC_ash makes up to 16% of the present-day global riverine FOC flux to the oceans. This reflects a substantial impact of anthropogenic activities on the fluxes and burial of fossil organic carbon that has been made less reactive than the rocks from which it was derived.

Fossil particulate organic carbon (FOC) is a geologically stable form of carbon that was produced by the ancient biosphere and then buried and stored in the lithosphere; it is a key player in the geological carbon cycle (1–7). Uplift and erosion liberate FOC from bedrock, delivering it to the surficial carbon cycle. Some is oxidized in sediment routing systems, but a portion escapes and can be transported by rivers to the oceans (5, 8–10). Oxidation of FOC represents a long-term atmospheric carbon source and O₂ sink, whereas the reburial of FOC in sedimentary basins has no long-term net effect on atmospheric CO₂ and O₂ (1, 9, 11). Exhumation and erosion of bedrock provide a natural source of FOC (2, 8), which we refer to as FOC_rock. Human activities have introduced another form of FOC from the mining and combustion of coal. Burning coal emits CO₂ to the atmosphere but also leaves behind solid waste that contains substantial amounts of organic carbon (OC) that survives high-temperature combustion (12–14). This fossil-fuel-sourced carbon represents a poorly understood anthropogenic flux in the global carbon cycle; it also provides a major source of black carbon, which is a severe pollutant and climate-forcing agent (12–15).Previous studies sought to quantify black carbon in different terrestrial and marine environments and to distinguish fossil fuel versus forest fire sources (14–18). In this study, we focused on fly ash—the material left from incomplete coal combustion. As a major fossil fuel, coal supplies around 30% of global primary energy consumption (19, 20). Despite efforts to capture and utilize fly ash, a fraction enters soils and rivers; the resulting fossil OC from fly ash (FOC_ash) has become a measurable part of the contemporary carbon cycle (14). FOC_ash is also referred to as “unburned carbon” in fly ash (21–25); it provides a useful measure of combustion efficiency and the quality of fly ash as a building material (e.g., in concrete) (23–26). Industrial standards of FOC_ash content in fly ash have been established for material quality assurance (23, 24, 26, 27). However, the characteristics and fluxes of FOC_ash released to the environment, and how these compare to FOC_rock from bedrock erosion, remain less well understood.To fill this knowledge gap, we examined the Chang Jiang (Yangtze River) basin in China—a system that allowed us to evaluate the influence of FOC_ash on the carbon cycle at continental scales. In the 2000s, China became the largest coal-consuming country in the world, with an annual coal consumption of over 2,500 Mt, equating to ∼50% of worldwide consumption (19, 20, 28). Coal contributed over 60% of China’s national primary energy consumption through the 2000s. A significant portion of this coal (approximately one-third) was consumed in the Chang Jiang (CJ) basin, where China’s most populated and economically developed areas are located (29). Significant amounts of fly ash and FOC_ash continue to be produced and consumed in the CJ basin. To determine the human-induced FOC_ash flux, we investigated the FOC_ash cycle in the CJ basin. We characterized OC in a series of samples including fly ash, bedrock sedimentary shale, and river sediment through multiple geochemical analyses. We then estimated the CJ-exported FOC_ash flux and evaluated how human activities modulated FOC transfer at basin scales. We found that in the CJ basin, coal combustion and dam construction have conspired to boost the FOC_ash flux and reduce the FOC_rock flux carried by the CJ; as a result, these two fluxes converged over an interval of 60 y.     

Atomic-scale insights into quantum-order parameters in bismuth-doped iron garnet

Bismuth and rare earth elements have been identified as effective substituent elements in the iron garnet structure, allowing an enhancement in magneto-optical response by several orders of magnitude in the visible and near-infrared region. Various mechanisms have been proposed to account for such enhancement, but testing of these ideas is hampered by a lack of suitable experimental data, where information is required not only regarding the lattice sites where substituent atoms are located but also how these atoms affect various order parameters. Here, we show for a Bi-substituted lutetium iron garnet how a suite of advanced electron microscopy techniques, combined with theoretical calculations, can be used to determine the interactions between a range of quantum-order parameters, including lattice, charge, spin, orbital, and crystal field splitting energy. In particular, we determine how the Bi distribution results in lattice distortions that are coupled with changes in electronic structure at certain lattice sites. These results reveal that these lattice distortions result in a decrease in the crystal-field splitting energies at Fe sites and in a lifted orbital degeneracy at octahedral sites, while the antiferromagnetic spin order remains preserved, thereby contributing to enhanced magneto-optical response in bismuth-substituted iron garnet. The combination of subangstrom imaging techniques and atomic-scale spectroscopy opens up possibilities for revealing insights into hidden coupling effects between multiple quantum-order parameters, thereby further guiding research and development for a wide range of complex functional materials.

The element bismuth has been chosen as a substituent, or major element, in a diverse range of functional materials, including multiferroics, superconductors, and catalysts (1–3). On account of the often significantly improved performance and various unique phenomena when bismuth is introduced in functional materials, investigations on the local order parameters underpinning such effects have attracted considerable attention. In the past few years, it has been verified that bismuth doping is also an effective method to enhance the performance of magneto-optical devices (4, 5). Among the iron oxides, ferrimagnetic insulators with the complex iron garnet structure R₃Fe₅O₁₂ (where R is an element with large radius) are already widely utilized in magneto-optic devices owing to their combination of small spin-wave damping, good optical transparency, and a pronounced Faraday effect (6–12). The strength of the Faraday effect, which describes a rotation of the plane of polarization of electromagnetic radiation in a magnetic field, is linearly proportional to the Verdet constant (13, 14) for a given material, which for magneto-optical materials such as substituted garnets depends strongly on the coupling effect of multiple quantum-order parameters (15, 16), including those of lattice, spin, and electronic orbitals (12, 17, 18). In particular, diverse polyhedral sites in the garnet structure are bridged via oxygen atoms with a strong exchange interaction effect, resulting in complex electronic and crystal structures (19–22). Although pure yttrium iron garnet (YIG) has several advantages in terms of magneto-optical response, it has not been widely applied in integrated devices due to its low Verdet constant, resulting in a limited Faraday rotation (23, 24). Due, however, to its chemical flexibility, selective substitution has been established as an effective method to tune various physical properties of iron garnets (7, 12, 25, 26), and it is noteworthy that Bi-substituted lutetium iron garnet films prepared via liquid phase epitaxy (LPE) demonstrate an appreciable enhancement in magneto-optical performance (8). Several models based on diamagnetic transitions have been proposed to explain the effect of Bi substitution on magneto-optical response (4, 12, 17, 19, 21, 27–30), in each case with a strong dependence on the crystal energy levels of the Fe³⁺ ions in differently coordinated lattice sites. There is still, however, a lack of experimental evidence to test these models, as this requires the distribution of substituent atoms to be characterized and related to their effect on the crystal lattice and electronic structure at different lattice sites. In this work, we address this limitation by the use of several advanced electron microscopy techniques (31–40) applied synergistically to a Bi-substituted lutetium iron garnet.     

An isolated water droplet in the aqueous solution of a supramolecular tetrahedral cage

Water under nanoconfinement at ambient conditions has exhibited low-dimensional ice formation and liquid–solid phase transitions, but with structural and dynamical signatures that map onto known regions of water’s phase diagram. Using terahertz (THz) absorption spectroscopy and ab initio molecular dynamics, we have investigated the ambient water confined in a supramolecular tetrahedral assembly, and determined that a dynamically distinct network of 9 ± 1 water molecules is present within the nanocavity of the host. The low-frequency absorption spectrum and theoretical analysis of the water in the Ga₄L₆¹²⁻ host demonstrate that the structure and dynamics of the encapsulated droplet is distinct from any known phase of water. A further inference is that the release of the highly unusual encapsulated water droplet creates a strong thermodynamic driver for the high-affinity binding of guests in aqueous solution for the Ga₄L₆¹²⁻ supramolecular construct.

Supramolecular capsules create internal cavities that are thought to act like enzyme active sites (1). As aqueous enzymes provide inspiration for the design of supramolecular catalysts, one of the goals of supramolecular chemistry is the creation of synthetic “receptors” that have both a high affinity and a high selectivity for the binding of guests in water (2, 3). The Ga₄L₆¹²⁻ tetrahedral assembly formulated by Raymond and coworkers represents an excellent example of a water-soluble supramolecular cage that has provided host interactions that promotes guest encapsulation. Using steric interactions and electrostatic charge to chemically position the substrate while shielding the reaction from solvent, this host has been shown to provide enhanced reaction rates that approach the performance of natural biocatalysts (4–10). Moreover, aqueous solvation of the substrate, host, and encapsulated solvent also play an important role in the whole catalytic cycle. In particular, the driving forces that release water from the nanocage host to favor the direct binding with the substrate is thought to be a critical factor in successful catalysis, but is challenging to probe directly (7, 8, 11–14).In both natural and artificial nanometer-sized environments, confined water displays uniquely modified structure and dynamics with respect to the bulk liquid (15–18). Recently, these modified properties were also found to have significant implications for the mechanism and energetics of reactions taking place in confined water with respect to those observed in bulk aqueous solution (19–21). In a pioneering study on supramolecular assemblies, Cram and collaborators (22) concluded that the interior of those cages is a “new and unique phase of matter” for the incarcerated guests. In more recent studies, it was postulated that, similar to graphitic and zeolite nanopores (23, 24), confined water within supramolecular host cavities is organized in stable small clusters [(H₂O)_n, with n = 8 to 19] that are different from gas phase water clusters (25). In these studies, the hydrogen-bonded water clusters were reported to be mostly ice- or clathrate-like by X-ray and neutron diffraction in the solid state at both ambient and cryogenic temperatures (26–32). However, to the best of our knowledge, such investigations have not characterized the Ga₄L₆¹²⁻ supramolecular tetrahedral assembly in the liquid state near room temperature and pressure, where the [Ga₄L₆]¹²⁻ capsule can perform catalytic reactions (6, 8, 9).Here, we use terahertz (THz) absorption spectroscopy and ab initio molecular dynamics (AIMD) to characterize low-frequency vibrations and structural organization of water in the nanoconfined environment. THz is ideally suited to probe the intermolecular collective dynamics of the water hydrogen bond (HB) network with extremely high sensitivity, as illustrated for different phases of water (33–38), and for aqueous solutions of salts, osmolytes, alcohols, and amino acids (36, 39–42). The THz spectra of the water inside the nanocage has been quantitatively reproduced with AIMD, allowing us to confidently characterize the water network in the cage in order to provide a more complete dynamical, structural, and thermodynamic picture. We have determined that the spectroscopic signature of the confined water in the nanocage is a dynamically arrested state whose structure bears none of the features of water at any alternate thermodynamic state point such as pressurized liquid or ice. Our experimental and theoretical study provides insight into the role played by encapsulated water in supramolecular catalysis, creating a low entropy and low enthalpy water droplet readily displaced by a catalytic substrate.     

Manipulating Berry curvature of SrRuO3 thin films via epitaxial strain

Berry curvature plays a crucial role in exotic electronic states of quantum materials, such as the intrinsic anomalous Hall effect. As Berry curvature is highly sensitive to subtle changes of electronic band structures, it can be finely tuned via external stimulus. Here, we demonstrate in SrRuO₃ thin films that both the magnitude and sign of anomalous Hall resistivity can be effectively controlled with epitaxial strain. Our first-principles calculations reveal that epitaxial strain induces an additional crystal field splitting and changes the order of Ru d orbital energies, which alters the Berry curvature and leads to the sign and magnitude change of anomalous Hall conductivity. Furthermore, we show that the rotation of the Ru magnetic moment in real space of a tensile-strained sample can result in an exotic nonmonotonic change of anomalous Hall resistivity with the sweeping of magnetic field, resembling the topological Hall effect observed in noncoplanar spin systems. These findings not only deepen our understanding of anomalous Hall effect in SrRuO₃ systems but also provide an effective tuning knob to manipulate Berry curvature and related physical properties in a wide range of quantum materials.

Over the past decades, Berry phase and Berry curvature have become an important ingredient in condensed matter physics, underlying a spectrum of phenomena such as ferroelectric polarization, orbital magnetism, and various Hall effects (1–5). In material systems that lack time-reversal symmetry or space-inversion symmetry or both, electrons acquire an anomalous velocity that is transverse to the external electric field and consequently gives rise to an anomalous Hall current, which contributes to intrinsic anomalous Hall effect (AHE) (6–10). Specifically, the intrinsic contribution of AHE is determined by the integration of Berry curvature over all the occupied electronic bands in the entire Brillouin zone. Therefore, its sign and magnitude highly depend on the topology of electronic band structure. Especially in a ferromagnetic material with sizable spin-orbit coupling (SOC), the Berry curvature can be substantially increased by an avoided band crossing near the Fermi level, leading to a considerable contribution to AHE (11–16). Thus, the evolution of intrinsic AHE represents a convenient probe to understand how the electronic structure changes Berry curvature under external stimulus.Transition metal oxide SrRuO₃ provides an ideal platform to investigate Berry curvature, because it is a 4d metallic ferromagnet with a sizable SOC (17–20), in which the AHE mainly arises from the Berry curvature of its electronic band structure (11, 21, 22). Due to the strong coupling between lattice distortions and electronic structure in transition metal oxides, previous studies have already revealed that epitaxial strain has profound effects on magnetic properties of SrRuO₃ films (23–32). These results suggest that epitaxial strain might be an effective approach to manipulating Berry curvature and related AHE in SrRuO₃ thin films, which, however, has not been comprehensively investigated yet. Besides, motivated by recent observations of unconventional Hall effect with a pronounced hump feature in SrRuO₃ ultrathin films and heterostructures (33–39), the underlying mechanism in which whether it belongs to trivial AHE caused by Berry curvature or exotic topological Hall effect due to noncoplanar spin textures is currently under intensive debate.In this work, we carry out systemic transport studies and detailed first-principles calculations to investigate the AHE in both tensile- and compressive-strained SrRuO₃ pseudocubic (001)-orientated thin films. We find that 1) as the epitaxial strain changes from compressive to tensile, SrRuO₃ thin films exhibit a robust ferromagnetic state, but their magnetic easy axis evolves from out-of-plane direction toward in-plane direction. 2) The saturated anomalous Hall resistivity (or conductivity) of SrRuO₃ thin films changes both its sign and magnitude with epitaxial strain. Theoretical calculations reveal that epitaxial strain induces an additional crystal field splitting and changes the order of Ru d orbital energies, which results in the sign and magnitude change of the anomalous Hall conductivity. 3) In SrRuO₃ thin films under tensile strain, rotation of Ru magnetic moments in real space with magnetic field affect the Berry curvature, which leads to a nonmonotonic change of the anomalous Hall resistivity at the intermediate field region. While this AHE signal resembles the exotic “hump feature” observed in other systems, its underlying mechanism is directly correlated with the evolution of Berry curvature with spin rotation. These results altogether demonstrate that epitaxial strain is a powerful approach to tuning the underlying electronic state, Berry curvature and thus AHE in a wide range of quantum materials.     

The evolution of red color vision is linked to coordinated rhodopsin tuning in lycaenid butterflies

Color vision has evolved multiple times in both vertebrates and invertebrates and is largely determined by the number and variation in spectral sensitivities of distinct opsin subclasses. However, because of the difficulty of expressing long-wavelength (LW) invertebrate opsins in vitro, our understanding of the molecular basis of functional shifts in opsin spectral sensitivities has been biased toward research primarily in vertebrates. This has restricted our ability to address whether invertebrate G_q protein-coupled opsins function in a novel or convergent way compared to vertebrate G_t opsins. Here we develop a robust heterologous expression system to purify invertebrate rhodopsins, identify specific amino acid changes responsible for adaptive spectral tuning, and pinpoint how molecular variation in invertebrate opsins underlie wavelength sensitivity shifts that enhance visual perception. By combining functional and optophysiological approaches, we disentangle the relative contributions of lateral filtering pigments from red-shifted LW and blue short-wavelength opsins expressed in distinct photoreceptor cells of individual ommatidia. We use in situ hybridization to visualize six ommatidial classes in the compound eye of a lycaenid butterfly with a four-opsin visual system. We show experimentally that certain key tuning residues underlying green spectral shifts in blue opsin paralogs have evolved repeatedly among short-wavelength opsin lineages. Taken together, our results demonstrate the interplay between regulatory and adaptive evolution at multiple G_q opsin loci, as well as how coordinated spectral shifts in LW and blue opsins can act together to enhance insect spectral sensitivity at blue and red wavelengths for visual performance adaptation.

Opsins belong to a diverse multigene family of G protein-coupled receptors that bind to a small nonprotein retinal moiety to form photosensitive rhodopsins and enable vision across animals (1–4). The tight relationship between opsin genotypes and spectral sensitivity phenotypes offers an ideal framework to analyze how specific molecular changes give rise to adaptations in visual behaviors (5). Notably, independent opsin gene gains and losses (6–13), genetic variation across opsins (14–16), spectral tuning mutations within opsins (17–21), and alterations in visual regulatory networks (22, 23) have contributed to opsin adaptation. Yet, the molecular and structural changes underlying the remarkable diversification of spectral sensitivity phenotypes identified in some invertebrates, including crustaceans and insects (24–27), are far less understood than those in vertebrate lineages (28–32).The diversity of opsin-based photoreceptors observed across animal visual systems is produced by distinct ciliary vertebrate c-opsin and invertebrate rhabdomeric based r-opsin subfamilies that mediate separate phototransduction cascades (31, 33–35). Vertebrate c-opsins function through the G protein transducing (G_t) signaling pathway, which activates cyclic nucleotide phosphodiesterase, ultimately resulting in a hyperpolarization response in photoreceptor cells through the opening of selective K⁺ channels (31, 36). By contrast, insect opsins transmit light stimuli through a G_q-type G protein (33, 37) with phosphoinositol (PLCβ) acting as an effector enzyme to achieve TRP channel depolarization in the invertebrate photoreceptor cell (34, 38).All vertebrate visual cone opsins derive from four gene families: short-wavelength-sensitive opsins SWS1 (or ultraviolet [UV]) with λ_max 344 to 445 nm and SWS2 with λ_max 400 to 470 nm, and longer-wavelength-sensitive opsins that specify the green MWS (or Rh2) pigments with λ_max 480 to 530 nm and red-sensitive LWS pigments with λ_max 500 to 570 nm (5, 30). Most birds and fish have retained the four ancestral opsin genes (39), with notable opsin expansions in cichlid fish opsins (23, 40), whereas SWS1 is extinct in monotremes, and SWS2 and M opsins are lost in marsupials and eutherian mammals (41). In primates, trichromatic vision is conferred through SWS1 (λ_max = 414 nm) and recent duplicate MWS (λ_max = 530 nm) and LWS opsins (λ_max = 560 nm) (42–44). In vertebrates, molecular evolutionary approaches and well-established in vitro opsin purification have identified the complex interplay between opsin duplications, regulatory and protein-coding mutations controlling opsin gene tuning, and spectral phenotypes notably in birds, fish, and mammals (45–47).Insect opsins are phylogenetically distinct but functionally analogous to those of vertebrates, and the ancestral opsin repertoire consists of three types of light-absorbing rhabdomeric G_q-type opsin specifying UV (350 nm), short-wavelength (blue, 440 nm) and long-wavelength pigments (LW, 530 nm) (48). Given the importance of color-guided behaviors and the remarkable photoreceptor spectral diversity observed in insects (26, 27), the dynamic opsin gene diversification found across lineages (Fig. 1) highlights their potentially central role in adaptation (27, 49, 50), yet the molecular basis of opsin functionality of rhabdomeric invertebrate G_q opsins remains understudied.Open in a separate windowFig. 1.Visual opsin gene evolution and spectral tuning mechanisms in insects. Visual opsin genes of the Atala hairstreak (E. atala, Lepidoptera, Lycaenidae) in comparison with those encoded in the genomes of diverse insects. The opsin types are highlighted in gray for UV, in blue for short wavelength (SW), and in green for long wavelength (LW). Numbers indicate multiple opsins, whereas no dot indicates gene loss. Colored circles indicate instances of shifted spectral sensitivities in at least one of the encoded opsins. The direction of shift is inferred from the opsin lambda max that departs from the typical range of absorbance in the opsin subfamily using wavelength boundaries for the various colors: UV <380 nm, violet 380 to 435 nm, blue 435 to 492 nm, green 492 to 530 nm, and red shifted >530 nm. Coleopteran lineages, and some hemipterans, lost the blue opsin locus and compensated for the loss of blue sensitivity via UV and/or LW gene duplications across lineages (11, 12). In butterflies, extended photosensitivity at short wavelengths is observed in Heliconius erato with two UV opsins at λ_max = 355 nm and 398 nm (10) and in P. rapae with two blue opsins with λ_max = 420 and 450 nm (17). A blue opsin duplication occurred independently in lycaenid butterflies (61). LW opsin duplications occurred independently in most major insect lineages (6, 16, 55) and confer a variable range of LW sensitivities with or without additional contributions from lateral filtering. In order to extend spectral sensitivity at longer wavelengths while sharpening blue acuity, some lycaenid butterflies have evolved a new color vision mechanism combining spectral shifts at a duplicate blue opsin and at the LW opsin. Images credit: Christopher Adams (illustrator).The recurrent evolution of red receptors in insects in particular suggests that perception of longer wavelengths can play an important role in the context of foraging, oviposition, and/or conspecific recognition (6, 27, 51–54). In butterflies, several mechanisms are likely to have provided extended spectral sensitivity to longer wavelengths. LW opsin duplications along with the evolution of lateral filtering between ommatidia has been demonstrated in two papilionids, Papilio xuthus (27) and Graphium sarpedon (55), as well as in a riodinid (Apodemia mormo) (6, 54). Lateral filtering pigments are relatively widespread across butterfly lineages, e.g., Heliconius (56), Pieris (57), Colias erate (58), and some moths [Adoxophyes orana (59) and Paysandisia archon (60)]. These pigments absorb short wavelengths and aid in shifting the sensitivity peak of green LW photoreceptors to longer wavelengths (27, 51, 56, 57, 61, 62). Despite creating distinct spectral types that can contribute to color vision, as identified in nymphalid (56), pierid (57), and lycaenid (62) species, all of which lack duplicated LW opsins (61, 63), lateral filtering alone cannot extend photoreceptor sensitivity toward the far red (700 to 750 nm) beyond the exponentially decaying long-wavelength rhodopsin absorbance spectrum (51). Thus, molecular variation of ancestral LW opsin genes is likely to have contributed an as yet underexplored mechanism to the diversification of long-wavelength photoreceptor spectral sensitivity. However, disentangling the relative contributions of lateral filtering and pure LW opsin properties has remained technically challenging using classical electrophysiological approaches (14, 64, although see, e.g., refs. 65, 66, 67) and has been limited by the lack of in vitro expression systems suitable for LW opsins.While opsin duplicates have been identified in numerous organisms, the spectral tuning mechanisms and interplay between new opsin photoreceptors in invertebrate visual system evolution are less well understood. Here we combine physiological, molecular, and heterologous approaches to start closing this gap in our knowledge of invertebrate G_q opsin evolution by investigating the functions, spectral tuning, and implications of evolving new combinations of short- and long-wavelength opsin types in lycaenid species. This butterfly group, comprising the famous blues, coppers, and hairstreaks, is the second largest family with about 5,200 (28%) of the some 18,770 described butterfly species (68). In light of their remarkable behavioral, ecological, and morphological diversity (69, 70), as well as pioneer studies in the Lycaena and Polyommatus genera supporting the rapid evolution of color vision in certain lineages (56, 61, 62), lycaenids provide an ideal candidate system for investigating opsin evolution and visual adaptations. Using the Atala hairstreak, Eumaeus atala, as a molecular and ecological model, we find coordinated spectral shifts at short- and long-wavelength G_q opsin loci and demonstrate that the combination of six ommatidial classes of photoreceptors in the compound eye uniquely extend spectral sensitivity at long wavelengths toward the far-red while concurrently sharpening acuity of multiple blue wavelengths. Together, these findings link the evolution of four-opsin visual systems to adaptation in the context of finely tuned color perception critical to the behavior of these butterflies.     

First-in-class humanized FSH blocking antibody targets bone and fat

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a K_D of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH–FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHβ subunit, which is sufficient to block its interaction with the FSH receptor. In doing so, the humanized antibody profoundly inhibited FSH action in cell-based assays, a prelude to further preclinical and clinical testing.

Obesity and osteoporosis affect nearly 650 million and 200 million people worldwide, respectively (1, 2). Yet the armamentarium for preventing and treating these disorders remains limited, particularly when compared with public health epidemics of a similar magnitude. It has also become increasingly clear that obesity and osteoporosis track together clinically. First, body mass does not protect against bone loss; instead, obesity can be permissive to osteoporosis and a high fracture risk (3, 4). Furthermore, the menopausal transition marks the onset not only of rapid bone loss, but also of visceral obesity and dysregulated energy balance (5–9). These physiologic aberrations have been attributed traditionally to a decline in serum estrogen, although, during the perimenopause—2 to 3 y prior to the last menstrual period—serum estrogen is within the normal range, while FSH levels rise to compensate for reduced ovarian reserve (10–12). In our view, therefore, the early skeletal and metabolic derangements cannot conceivably be explained solely by declining estrogen (13, 14).The past decade has shown that pituitary hormones can act directly on the skeleton and other tissues, a paradigm shift that is in stark contrast to previously held views on their sole regulation of endocrine targets (15–25). We and others have shown that FSH can bypass the ovary to act on G_i-coupled FSH receptors (FSHRs) on osteoclasts to stimulate bone resorption and inhibit bone formation (26, 27). This mechanism, which could underscore the bone loss during early menopause, is testified by the strong correlations between serum FSH, bone turnover, and bone mineral density (7–9, 14, 16, 26). Likewise, activating polymorphisms in the FSHR in postmenopausal women are linked to a high bone turnover and reduced bone mass (27). It therefore made biological and clinical sense to inhibit FSH action during this period to prevent bone loss.Toward this goal, we generated murine polyclonal and monoclonal antibodies to a 13-amino-acid–long binding epitope of FSHβ (28–31). The mouse and human FSHβ epitopes differ by just two amino acids; hence, blocking antibodies to the human epitope showed efficacy in mice (28). The antibodies displayed two sets of actions: they attenuated the loss of bone after ovariectomy by inhibiting bone resorption and stimulating bone formation and displayed profound effects on body composition and energy metabolism (28, 29, 31). Most notably, in a series of contemporaneously reproduced experiments, we (M.Z. and C.J.R.) found that FSH blockade reduced body fat, triggered adipocyte beiging, and increased thermogenesis in models of obesity, notably post ovariectomy and after high-fat diet (29). Our findings have been further confirmed independently by two groups who used a FSHβ–GST fusion protein or tandem repeats of the 13-amino-acid–long FSHβ epitope for studies on bone and fat, respectively (32, 33). Consistent with the mouse data, inhibiting FSH secretion using a GnRH agonist in prostate cancer patients resulted in low body fat compared with orchiectomy, wherein FSH levels are high (34). This interventional clinical trial provides evidence for a therapeutic benefit of reducing FSH levels on body fat in people. There is also new evidence that FSH blockade lowers serum cholesterol (35, 36).Thus, both emerging and validated datasets on the antiobesity, osteoprotective, and lipid-lowering actions of FSH blockade in mice and in humans prompted our current attempt to develop and characterize an array of fully humanized FSH-blocking antibodies for future testing in people. Here, we report that our lead first-in-class humanized antibody, Hu6, and two related molecules, Hu26 and Hu28, bind human FSH with a high affinity (K_Ds <10 nM), block the binding of FSH on the human FSHR, and inhibit FSH action in functional cell-based assays.     

Cholinergic suppression of hippocampal sharp-wave ripples impairs working memory

Learning and memory are assumed to be supported by mechanisms that involve cholinergic transmission and hippocampal theta. Using G protein–coupled receptor-activation–based acetylcholine sensor (GRAB_ACh3.0) with a fiber-photometric fluorescence readout in mice, we found that cholinergic signaling in the hippocampus increased in parallel with theta/gamma power during walking and REM sleep, while ACh3.0 signal reached a minimum during hippocampal sharp-wave ripples (SPW-R). Unexpectedly, memory performance was impaired in a hippocampus-dependent spontaneous alternation task by selective optogenetic stimulation of medial septal cholinergic neurons when the stimulation was applied in the delay area but not in the central (choice) arm of the maze. Parallel with the decreased performance, optogenetic stimulation decreased the incidence of SPW-Rs. These findings suggest that septo–hippocampal interactions play a task-phase–dependent dual role in the maintenance of memory performance, including not only theta mechanisms but also SPW-Rs.

The neurotransmitter acetylcholine is thought to be critical for hippocampus-dependent declarative memories (1, 2). Reduction in cholinergic neurotransmission, either in Alzheimer’s disease or in experiments with cholinergic antagonists, such as scopolamine, impairs memory function (3–8). Acetylcholine may bring about its beneficial effects on memory encoding by enhancing theta rhythm oscillations, decreasing recurrent excitation, and increasing synaptic plasticity (9–11). Conversely, drugs which activate cholinergic receptors enhance learning and, therefore, are a neuropharmacological target for the treatment of memory deficits in Alzheimer’s disease (5, 12, 13).The contribution of cholinergic mechanisms in the acquisition of long-term memories and the role of the hippocampal–entorhinal–cortical interactions are well supported by experimental data (5, 12, 13). In addition, working memory or “short-term” memory is also supported by the hippocampal–entorhinal–prefrontal cortex (14–16). Working memory in humans is postulated to be a conscious process to “keep things in mind” transiently (16). In rodents, matching to sample task, spontaneous alternation between reward locations, and the radial maze task have been suggested to function as a homolog of working memory [“working memory like” (17)].Cholinergic activity is a critical requirement for working memory (18, 19) and for sustaining theta oscillations (10, 20–22). In support of this contention, theta–gamma coupling and gamma power are significantly higher in the choice arm of the maze, compared with those in the side arms where working memory is no longer needed for correct performance (23–26). It has long been hypothesized that working memory is maintained by persistent firing of neurons, which keep the presented items in a transient store in the prefrontal cortex and hippocampal–entorhinal system (27–31), although the exact mechanisms are debated (32–37). An alternative hypothesis holds that items of working memory are stored in theta-nested gamma cycles (38). Common in these models of working memory is the need for an active, cholinergic system–dependent mechanism (39–41). However, in spontaneous alternation tasks, the animals are not moving continuously during the delay, and theta oscillations are not sustained either. During the immobility epochs, theta is replaced by intermittent sharp-wave ripples (SPW-R), yet memory performance does not deteriorate. On the contrary, artificial blockade of SPW-Rs can impair memory performance (42, 43), and prolongation of SPW-Rs improves performance (44). Under the cholinergic hypothesis of working memory, such a result is unexpected.To address the relationship between cholinergic/theta versus SPW-R mechanism in spontaneous alternation, we used a G protein–coupled receptor-activation–based acetylcholine sensor (GRAB_ACh3.0) (45) to monitor acetylcholine (ACh) activity during memory performance in mice. In addition, we optogenetically enhanced cholinergic tone, which suppresses SPW-Rs by a different mechanism than electrically or optogenetically induced silencing of neurons in the hippocampus (43, 44). We show that cholinergic signaling in the hippocampus increases in parallel with theta power/score during walking and rapid eye movement (REM) sleep and reaches a transient minimum during SPW-Rs. Selective optogenetic stimulation of medial septal cholinergic neurons decreased the incidence of SPW-Rs during non-REM sleep (46–48), as well as during the delay epoch of a working memory task and impaired memory performance. These findings demonstrate that memory performance is supported by complementary theta and SPW-R mechanisms.     

Stimulation of soil respiration by elevated CO2 is enhanced under nitrogen limitation in a decade-long grassland study

Whether and how CO₂ and nitrogen (N) availability interact to influence carbon (C) cycling processes such as soil respiration remains a question of considerable uncertainty in projecting future C–climate feedbacks, which are strongly influenced by multiple global change drivers, including elevated atmospheric CO₂ concentrations (eCO₂) and increased N deposition. However, because decades of research on the responses of ecosystems to eCO₂ and N enrichment have been done largely independently, their interactive effects on soil respiratory CO₂ efflux remain unresolved. Here, we show that in a multifactor free-air CO₂ enrichment experiment, BioCON (Biodiversity, CO₂, and N deposition) in Minnesota, the positive response of soil respiration to eCO₂ gradually strengthened at ambient (low) N supply but not enriched (high) N supply for the 12-y experimental period from 1998 to 2009. In contrast to earlier years, eCO₂ stimulated soil respiration twice as much at low than at high N supply from 2006 to 2009. In parallel, microbial C degradation genes were significantly boosted by eCO₂ at low but not high N supply. Incorporating those functional genes into a coupled C–N ecosystem model reduced model parameter uncertainty and improved the projections of the effects of different CO₂ and N levels on soil respiration. If our observed results generalize to other ecosystems, they imply widely positive effects of eCO₂ on soil respiration even in infertile systems.

Elevation of atmospheric CO₂ concentrations, owing to fossil fuel combustion and land-use changes, represents one of the greatest scientific and political concerns of the 21st century (1). Carbon (C) movement into the atmosphere annually from soils (i.e., soil CO₂ efflux or soil respiration) is much larger than annual C emissions from fossil fuel combustion (2), and thus even small changes in soil respiration could have significant impacts on the pace of change in atmospheric CO₂. Numerous studies have demonstrated that elevated CO₂ (eCO₂) has a direct stimulatory effect on rates of plant photosynthesis (3), and an indirect positive effect on soil respiration, which typically includes autotrophic respiration from plant roots and heterotrophic respiration from microbial decomposition of litter and soil organic matter (SOM). The eCO₂ stimulatory effect on soil respiration is commonly attributed to the following three mutually nonexclusive mechanisms from the actions of plants and microorganisms (4–7): enhanced root respiration associated with greater belowground plant biomass, enhanced microbial decomposition of fresh C due to greater supply of foliar and root-derived labile soil C, and increased microbial priming of old SOM fueled by this increased supply of labile soil C (4, 5). The stimulation of soil respiration by eCO₂ (7, 8) has the potential to greatly accelerate the future rate of increase in atmospheric CO₂ concentrations unless matched by an offsetting increase in net C uptake.Human activities have also increased nitrogen (N) deposition to natural ecosystems (9). N enrichment is a growing concern because it disturbs N-cycle processes in many ecosystems (9). Various studies have suggested that N addition can either increase (10, 11) or reduce (12–15) soil CO₂ efflux, while other studies have suggested that N addition does not influence soil CO₂ efflux (16, 17), depending on ecosystem type and season of the year.The stimulation of soil respiration by eCO₂ also could be strongly influenced by variability in ambient soil N availability and the rate of atmospheric N deposition (18). However, studies that have explored the interactive effects of eCO₂ and N on soil respiration are extremely scarce. For instance, an open-top study of young subtropical tree seedlings in contrasting eCO₂ and N treatments in transplanted soil found that response to eCO₂ was enhanced by high levels of N addition (10 g⋅m⁻²⋅y⁻¹) in the earliest 2 y but unaffected by the same N supply in the subsequent year (19, 20). A free-air enrichment study in perennial grasslands also found no interaction between eCO₂ and N addition treatments over the first 2 y of the study (21). Given that many questions about such potential interactions remain unresolved (22), here we report on 12 y of results in that same grassland study, assessing whether interactions develop and, if so, what underlying mechanisms might drive them.It is well known that N availability alters many aspects of ecosystems (12, 23, 24) and thus could hypothetically influence responses of soil respiration to eCO₂. Three potentially off-setting and interrelated mechanisms have been proposed. First, N limitation could affect belowground productivity and thus root respiration. For example, if N limitation constrains plant canopy development and the stimulatory effect of eCO₂ on photosynthesis, and thus limits total productivity belowground, root respiration will decline (24). On the other hand, the same N limitation constraint on canopy development combined with stimulatory effects of eCO₂ on photosynthesis could increase plant investment of C in nutrient-absorbing systems (25, 26), favoring C allocation to roots at the expense of aboveground biomass. Such a shift in allocation could increase root respiration (27). Second, changes in root detrital production and exudation of labile C into soils can influence substrate supply that fuels soil microbial activity and heterotrophic respiration. Third, the supply of labile C into soils can influence decomposition of SOM through the priming effect, which would also influence soil heterotrophic respiration (28). Under N limitation, greater photosynthesis caused by eCO₂ could stimulate mining of N from SOM, and thus soil heterotrophic respiration, through enhanced priming mechanisms (29).Although various studies indicate that N availability plays critical roles in mediating soil respiration (10–17, 23, 30, 31), divergent results are observed: positive (10, 11, 23), neutral (16, 17, 30), or negative (12–15, 30, 31). Thus, the impacts of N availability on the magnitude and duration of the eCO₂ enhancement of soil respiration and its underlying mechanisms remain elusive, particularly under field settings. In addition, recent modeling efforts demonstrated the importance of understanding microbial C decomposition for more confidently extrapolating soil C cycling processes (32, 33). However, to date, it remains uncertain whether and how microbial processes influence the responses of terrestrial ecosystems to eCO₂ and N deposition and how best to incorporate information regarding microbial responses to eCO₂ and N into climate-C models for better simulation and prediction (32, 34, 35).Herein, we report results from a well-replicated long-term (12 y at the time of sampling) CO₂ × N experiment, BioCON (Biodiversity, CO₂, and N deposition) (24), to elucidate the interactive effects of eCO₂ and N enrichment on soil respiration and their underlying mechanisms. From 1998 to 2009, we measured soil CO₂ efflux and other biogeochemical processes on 296 plots containing different numbers (1, 4, 9, or 16 species) and combinations (C₃ and C₄ grasses, forbs, and legumes) of perennial plant species at ambient CO₂ (aCO₂) or eCO₂ (+180 ppm) with either ambient N supply (aN) or enriched N supply (eN, i.e., +4 g N⋅m⁻²⋅y⁻¹). Hereafter, we refer to these four treatment combinations as aCO₂-aN, eCO₂-aN, aCO₂-eN, and eCO₂-eN. The contrasting high versus low levels of N supply in this study was a rough proxy for a part of the worldwide range of N supply rates in soils as well as for times or places with low versus high N deposition (24). Thus, we posit that the results are relevant to understanding the potentially different responses to eCO₂ of both low versus high N fertility soils and contexts with low versus high N deposition. In 2009, we also assessed responses of microbial community functional gene structure to eCO₂ and N enrichment to gain insights into microbial regulation of soil respiration. In addition, we incorporated microbial functional trait information into ecosystem models to explore means of better prediction of C cycling. Our overarching hypothesis is that N limitation would accelerate the stimulatory effects of eCO₂ on soil respiration, primarily via microbial N mining mechanisms. We further explored the possibility that microbial functional trait information would greatly help to constrain the uncertainty of model parameters and hence significantly improve confidence in model simulations and predictions.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor⁺ (LepR⁺) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

The maintenance and repair of the skeleton require the generation of new bone cells throughout adult life. Osteoblasts are relatively short-lived cells that are constantly regenerated, partly by skeletal stem cells within the bone marrow (1). The main source of new osteoblasts in adult bone marrow is leptin receptor-expressing (LepR⁺) stromal cells (2–4). These cells include the multipotent skeletal stem cells that give rise to the fibroblast colony-forming cells (CFU-Fs) in the bone marrow (2), as well as restricted osteogenic progenitors (5) and adipocyte progenitors (6–8). LepR⁺ cells are a major source of osteoblasts for fracture repair (2) and growth factors for hematopoietic stem cell maintenance (9–11).One growth factor synthesized by LepR⁺ cells, as well as osteoblasts and osteocytes, is osteolectin/Clec11a, a secreted glycoprotein of the C-type lectin domain superfamily (5, 12, 13). Osteolectin is an osteogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR⁺ cells into osteoblasts. Osteolectin acts by binding to integrin α11β1, which is selectively expressed by LepR⁺ cells and osteoblasts, activating the Wnt pathway (12). Deficiency for either Osteolectin or Itga11 (the gene that encodes integrin α11) reduces osteogenesis during adulthood and causes early-onset osteoporosis in mice (12, 13). Recombinant osteolectin promotes osteogenic differentiation by bone marrow stromal cells in culture and daily injection of mice with osteolectin systemically promotes bone formation.Osteoporosis is a progressive condition characterized by reduced bone mass and increased fracture risk (14). Several factors contribute to osteoporosis development, including aging, estrogen insufficiency, mechanical unloading, and prolonged glucocorticoid use (14). Existing therapies include antiresorptive agents that slow bone loss, such as bisphosphonates (15, 16) and estrogens (17), and anabolic agents that increase bone formation, such as parathyroid hormone (PTH) (18), PTH-related protein (19), and sclerostin inhibitor (SOSTi) (20). While these therapies increase bone mass and reduce fracture risk, they are not a cure.PTH promotes both anabolic and catabolic bone remodeling (21–24). PTH is synthesized by the parathyroid gland and regulates serum calcium levels, partly by regulating bone formation and bone resorption (23–25). PTH1R is a PTH receptor (26, 27) that is strongly expressed by LepR⁺ bone marrow stromal cells (8, 28–30). Recombinant human PTH (Teriparatide; amino acids 1 to 34) and synthetic PTH-related protein (Abaloparatide) are approved by the US Food and Drug Administration (FDA) for the treatment of osteoporosis (19, 31). Daily (intermittent) administration of PTH increases bone mass by promoting the differentiation of osteoblast progenitors, inhibiting osteoblast and osteocyte apoptosis, and reducing sclerostin levels (32–35). PTH promotes osteoblast differentiation by activating Wnt and BMP signaling in bone marrow stromal cells (28, 36, 37), although the mechanisms by which it regulates Wnt pathway activation are complex and uncertain (38).Sclerostin is a secreted glycoprotein that inhibits Wnt pathway activation by binding to LRP5/6, a widely expressed Wnt receptor (7, 8), reducing bone formation (39, 40). Sclerostin is secreted by osteocytes (8, 41), negatively regulating bone formation by inhibiting the differentiation of osteoblasts (41, 42). SOSTi (Romosozumab) is a humanized monoclonal antibody that binds sclerostin, preventing binding to LRP5/6 and increasing Wnt pathway activation and bone formation (43). It is FDA-approved for the treatment of osteoporosis (20, 44) and has activity in rodents in addition to humans (45, 46).The discovery that osteolectin is a bone-forming growth factor raises the question of whether it mediates the effects of PTH or SOSTi on osteogenesis.     

Circular swimming motility and disordered hyperuniform state in an algae system

Active matter comprises individually driven units that convert locally stored energy into mechanical motion. Interactions between driven units lead to a variety of nonequilibrium collective phenomena in active matter. One of such phenomena is anomalously large density fluctuations, which have been observed in both experiments and theories. Here we show that, on the contrary, density fluctuations in active matter can also be greatly suppressed. Our experiments are carried out with marine algae (Effrenium voratum), which swim in circles at the air–liquid interfaces with two different eukaryotic flagella. Cell swimming generates fluid flow that leads to effective repulsions between cells in the far field. The long-range nature of such repulsive interactions suppresses density fluctuations and generates disordered hyperuniform states under a wide range of density conditions. Emergence of hyperuniformity and associated scaling exponent are quantitatively reproduced in a numerical model whose main ingredients are effective hydrodynamic interactions and uncorrelated random cell motion. Our results demonstrate the existence of disordered hyperuniform states in active matter and suggest the possibility of using hydrodynamic flow for self-assembly in active matter.

Active matter exists over a wide range of spatial and temporal scales (1–6) from animal groups (7, 8) to robot swarms (9–11), to cell colonies and tissues (12–16), to cytoskeletal extracts (17–20), to man-made microswimmers (21–25). Constituent particles in active matter systems are driven out of thermal equilibrium at the individual level; they interact to develop a wealth of intriguing collective phenomena, including clustering (13, 22, 24), flocking (11, 26), swarming (12, 13), spontaneous flow (14, 20), and giant density fluctuations (10, 11). Many of these observed phenomena have been successfully described by particle-based or continuum models (1–6), which highlight the important roles of both individual motility and interparticle interactions in determining system dynamics.Current active matter research focuses primarily on linearly swimming particles which have a symmetric body and self-propel along one of the symmetry axes. However, a perfect alignment between the propulsion direction and body axis is rarely found in reality. Deviation from such a perfect alignment leads to a persistent curvature in the microswimmer trajectories; examples of such circle microswimmers include anisotropic artificial micromotors (27, 28), self-propelled nematic droplets (29, 30), magnetotactic bacteria and Janus particles in rotating external fields (31, 32), Janus particle in viscoelastic medium (33), and sperm and bacteria near interfaces (34, 35). Chiral motility of circle microswimmers, as predicted by theoretical and numerical investigations, can lead to a range of interesting collective phenomena in circular microswimmers, including vortex structures (36, 37), localization in traps (38), enhanced flocking (39), and hyperuniform states (40). However, experimental verifications of these predictions are limited (32, 35), a situation mainly due to the scarcity of suitable experimental systems.Here we address this challenge by investigating marine algae Effrenium voratum (41, 42). At air–liquid interfaces, E. voratum cells swim in circles via two eukaryotic flagella: a transverse flagellum encircling the cellular anteroposterior axis and a longitudinal one running posteriorly. Over a wide range of densities, circling E. voratum cells self-organize into disordered hyperuniform states with suppressed density fluctuations at large length scales. Hyperuniformity (43, 44) has been considered as a new form of material order which leads to novel functionalities (45–49); it has been observed in many systems, including avian photoreceptor patterns (50), amorphous ices (51), amorphous silica (52), ultracold atoms (53), soft matter systems (54–61), and stochastic models (62–64). Our work demonstrates the existence of hyperuniformity in active matter and shows that hydrodynamic interactions can be used to construct hyperuniform states.     

Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth

Vimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [Pt^II(C^N^N)(NHC^2Bu)]PF₆ (Pt1a; HC^N^N = 6-phenyl-2,2′-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.

Cancer invasion and metastasis are among the major causes of recurrence and mortality (1). Cancer metastasis begins with epithelial–mesenchymal transition (EMT), where epithelial cancer cells are transformed into mesenchymal cells equipped with motility, invasion, and stem cell-like properties (2–4). Vimentin (VIM), a canonical biomarker of EMT, is an intermediate filament protein playing pivotal roles in cytoskeletal architecture, organelle positioning, cell migration, and signaling; its overexpression in aggressive epithelial cancers of lung, breast, and prostate origin, and malignant melanoma, were reported to be associated with the acquisition of migratory and invasive phenotypes (5). The enhanced cell motility and invasiveness by VIM drive cancer cells’ spreading from primary tumor to distant organs through the bloodstream or lymphatic system, resulting in a metastatic cascade (6, 7). Emerging evidence showed that high levels of VIM predicted a poor prognosis, particularly in patients with nonsmall cell lung cancer and triple-negative breast cancer (8–10). In view of its clinical significance, targeting VIM is an appealing strategy to combat advanced metastatic cancers that do not respond well to traditional chemotherapy or antihormonal therapy. Nevertheless, inhibitors/disruptors of VIM are scarce in the literature. Moreover, studies on the biomolecular interactions between VIM and its binding partner(s) are underdeveloped.Several anticancer organic compounds have been reported to target VIM and display in vitro anticancer activities (11–14), but without mentioning their in vivo antimetastatic activity. Herein described are studies on the binding interaction of [Pt^II(C^N^N)(NHC^2Bu)]PF₆ (Pt1a, where HC^N^N = 6-phenyl-2,2′-bipyridine and NHC = N-heterocyclic carbene) with VIM, and the associated anticancer properties. This complex has a scaffold with NHC ligand being orthogonal to the pincer [Pt^II(C^N^N)] plane; such a unique structural scaffold renders Pt1a able to effectively bind to VIM noncovalently, in contrast to covalent modification by the majority of known VIM-targeting compounds. Our work features a rare example of an antitumor metal complex that engages VIM and shows promising in vivo antitumor activity in multiple mouse models bearing advanced metastatic tumors. This work also demonstrates an example of effective anticancer compound development by taking advantage of unique structural scaffolds of metal complexes for noncovalent interactions with an important molecular target of cancer as also revealed by recent work of Meggers, Che, Casini, and coworkers (15–20).