Natural gas shortages during the “coal-to-gas” transition in China have caused a large redistribution of air pollution in winter 2017

The Chinese “coal-to-gas” and “coal-to-electricity” strategies aim at reducing dispersed coal consumption and related air pollution by promoting the use of clean and low-carbon fuels in northern China. Here, we show that on top of meteorological influences, the effective emission mitigation measures achieved an average decrease of fine particulate matter (PM_2.5) concentrations of ∼14% in Beijing and surrounding areas (the “2+26” pilot cities) in winter 2017 compared to the same period of 2016, where the dispersed coal control measures contributed ∼60% of the total PM_2.5 reductions. However, the localized air quality improvement was accompanied by a contemporaneous ∼15% upsurge of PM_2.5 concentrations over large areas in southern China. We find that the pollution transfer that resulted from a shift in emissions was of a high likelihood caused by a natural gas shortage in the south due to the coal-to-gas transition in the north. The overall shortage of natural gas greatly jeopardized the air quality benefits of the coal-to-gas strategy in winter 2017 and reflects structural challenges and potential threats in China’s clean-energy transition.

The “airpocalypse” in China stems from a multitude of air pollutants (1–3) that are associated with significant climate and health effects (4–8). Eliminating the severe fine particulate matter (PM_2.5; particulate matter with a diameter smaller than 2.5 µm) pollution smog has been perceived as a national priority, with the establishment of a coal-consumption cap that required the share of coal in the national primary energy mix to drop to below 65% in 2017 by a transition to cleaner natural gas and nonfossil energy sources (9). Coal reduction is, however, the crux of China’s air pollution control (10). Fig. 1 shows the coal-control roadmap of China from 2010 through 2030. As of 2017, over half of the world’s coal consumption has occurred in China, accounting for ∼60% of the country’s primary energy consumption (11). After effective coal reductions from the power sector and key energy-intensive industries (phase I), the further coal control in China has been focusing on the reduction of dispersed coal use in residential and small industrial facilities (phase II). The dispersed coal (the so-called “Sanmei” in Chinese) refers to raw coal, usually a high-polluting fuel with high ash residue, burned in noncentralized combustion facilities without end-of-pipe air pollutant treatment. The residential dispersed coal combustion in vast rural areas has been estimated to be a major contributor to high PM_2.5 exposure and premature mortality in China (7, 12–14).Open in a separate windowFig. 1.The roadmap of coal control in China from 2010 to 2030. The light orange shaded area shows the share of coal in the primary energy mix for 2010–2030 (11) with three-phased coal controls (phase I: in the power section and key energy-intensive industries; phase II: toward dispersed coal reductions; and phase III: pertaining to clean-energy development). The black bars indicate the dispersed coal consumption for 2016–2018 and 2020 with source decomposition for sectoral changes (17). The doughnut charts show the primary energy structures of China in 2010, 2017, and 2030, respectively (11, 37). Note: Energy data for Hong Kong, Macau, and Taiwan are not included here.Since early 2017, a series of clean-heating actions have been implemented in Beijing and its neighboring provinces, especially in the “2+26” cities located along the air pollution transport channel of the Beijing–Tianjin–Hebei (BTH) region (Beijing, Tianjin, and 26 other cities in Hebei, Shanxi, Shandong, and Henan provinces) (15, 16). The major dispersed coal control measures include replacing traditional household coal-fired stoves with wall-mounted natural gas heaters (“coal-to-gas”) or electric stoves (“coal-to-electricity”) and eliminating the small industrial coal-fired steam boilers and construction materials industrial kilns (brick, ceramic, and lime industries) (17). The changes in coal consumption related to individual measures are given in Fig. 1.Combining the ground-based measurements, localized emission estimates, and chemical transport model simulations, we show that, although air pollution in the northern 2+26 pilot cities has been greatly improved by the emission mitigation measures, the coal-to-gas action in winter 2017 has caused a severe natural gas shortage in the rest of China (18, 19 and SI Appendix, section S1), which necessitated the use of more polluting alternative energy sources and led to a deteriorated air quality in the gas-shortage regions.     

Increasing risk of another Cape Town “Day Zero” drought in the 21st century

Three consecutive dry winters (2015–2017) in southwestern South Africa (SSA) resulted in the Cape Town “Day Zero” drought in early 2018. The contribution of anthropogenic global warming to this prolonged rainfall deficit has previously been evaluated through observations and climate models. However, model adequacy and insufficient horizontal resolution make it difficult to precisely quantify the changing likelihood of extreme droughts, given the small regional scale. Here, we use a high-resolution large ensemble to estimate the contribution of anthropogenic climate change to the probability of occurrence of multiyear SSA rainfall deficits in past and future decades. We find that anthropogenic climate change increased the likelihood of the 2015–2017 rainfall deficit by a factor of five to six. The probability of such an event will increase from 0.7 to 25% by the year 2100 under an intermediate-emission scenario (Shared Socioeconomic Pathway 2-4.5 [SSP2-4.5]) and to 80% under a high-emission scenario (SSP5-8.5). These results highlight the strong sensitivity of the drought risk in SSA to future anthropogenic emissions.

The Day Zero Cape Town drought was one of the worst water crises ever experienced in a metropolitan area (1, 2). Droughts are a regular occurrence in southwestern South Africa (SSA), having occurred during the late 1920s, early 1970s, and, more recently, during 2003–2004 (Fig. 1 A and B). However, the extended winter (April to September [AMJJAS]) 3-y rainfall deficit (Fig. 1 A and B; SI Appendix, Fig. S1) which drove the 2015–2017 Cape Town drought (2–8) was exceptional over the last century (4, 9). Storage in reservoirs supplying water to 3.7 million people in the Cape Town metropolitan area dropped to about 20% of capacity in May 2018. As a consequence, strict water-usage restrictions were implemented to delay water levels reaching 13.5%, the level at which much of the city’s municipal supply would have been disconnected (7), a scenario referred to as “Day Zero” by the municipal water authorities (7). Above-average winter rain over the rest of the 2018 austral winter allowed Cape Town to avoid the Day Zero scenario.Open in a separate windowFig. 1.(A) Mean 2015–2017 AMJJAS rainfall anomaly relative to 1921–1970. The dashed (continuous) line denotes negative anomalies beyond 1 (1.5) SD. (B) Time series of the observed (GPCC, blue; CRU, red) 3-y running mean AMJJAS WRI (Materials and Methods) from 1901 to 2017. The 2015–2017 mean is record-breaking over the period 1901–2017. (C–E) Mean 1921–1970 AMJJAS rainfall (millimeters per month) in observations (GPCC) (C), SPEAR_MED (D), and SPEAR_LO (E). The red lines encircle the area receiving at least 65% of the total annual rainfall during AMJJAS used to define WRI. (F) Monthly WRI in observations and models. Comparison of SPEAR_MED with SPEAR_LO shows how an enhanced resolution is key to capture finer-scale regional details of winter rainfall in the relatively small SSA Mediterranean region.While poor water-management practices and infrastructure deficiencies worsened the crisis (10, 11), the 2015–2017 rainfall deficit was the main driver of the drought (5). To facilitate the improvement of water-management practices and the infrastructure necessary to make the system more resilient, it is critical to first determine how likely a meteorological drought like the one in 2015–2017 might be in the coming decades. Increased aridity is expected in most of southern Africa (12–14) as a consequence of the Hadley Cell poleward expansion (4, 15–18) and southward shift of the Southern Hemisphere jet stream (19). Second, the risk of more extreme droughts should be quantified to understand the potential for emerging risks that could make a Day Zero event in Cape Town unavoidable.Previous work (5) has suggested that the Day Zero drought may have been made 1.4 to 6.4 times more likely over the last century due to +1 K of global warming, with the risk expected to scale linearly with one additional degree of warming. Such estimates make use of statistical models of the probability distribution’s tail (e.g., the generalized extreme value) applied to observations and previous-generation [i.e., as those participating to the Coupled Model Intercomparison Project Phase 3 (CMIP3) (20) and 5 (21)] climate models. CMIP3 and CMIP5 models have been shown to have a systematically biased position of the Southern Hemisphere jet stream toward the Equator, due to insufficient horizontal resolution (19). This produces a large uncertainty in model projections of jet-stream shifts (22, 23), thus hindering realistic projections of Southern Hemisphere climate change. Furthermore, for hydroclimatic variables, a statistical extrapolation of the probability distribution’s tail might have inherent limitations in providing precise estimates of the event probability of future extreme events, although its precision profits from the use of large ensembles (24, 25).Large ensembles of comprehensive climate models provide thousands of years of data that allow direct construction of the underlying probability distribution of hydroclimatic extremes without relying on a hypothesized statistical model of extremes (25, 26). South African winter rains have high interannual and decadal variability due to El Niño–Southern Oscillation (27), the Southern Annular Mode (28), and interdecadal variability (29). A multidecade to multicentury record may be required to detect the emergence of statistically significant trends in regional precipitation extremes. A large ensemble is, thus, a powerful method to isolate, at the decadal timescale, internal natural variability (e.g., SI Appendix, Fig. S2) from the forced signal (30–32).     

An engineered 4-1BBL fusion protein with “activity on demand”

Engineered cytokines are gaining importance in cancer therapy, but these products are often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as a target for therapeutic strategies with agonistic antibodies or using its cognate cytokine ligand, 4-1BBL. Here we describe the engineering of an antibody fusion protein, termed F8-4-1BBL, that does not exhibit cytokine activity in solution but regains biological activity on antigen binding. F8-4-1BBL bound specifically to its cognate antigen, the alternatively spliced EDA domain of fibronectin, and selectively localized to tumors in vivo, as evidenced by quantitative biodistribution experiments. The product promoted a potent antitumor activity in various mouse models of cancer without apparent toxicity at the doses used. F8-4-1BBL represents a prototype for antibody-cytokine fusion proteins, which conditionally display “activity on demand” properties at the site of disease on antigen binding and reduce toxicity to normal tissues.

Cytokines are immunomodulatory proteins that have been considered for pharmaceutical applications in the treatment of cancer patients (1–3) and other types of disease (2). There is a growing interest in the use of engineered cytokine products as anticancer drugs, capable of boosting the action of T cells and natural killer (NK) cells against tumors (3, 4), alone or in combination with immune checkpoint inhibitors (3, 5–7).Recombinant cytokine products on the market include interleukin-2 (IL-2) (Proleukin) (8, 9), IL-11 (Neumega) (10, 11), tumor necrosis factor (TNF; Beromun) (12), interferon (IFN)-α (Roferon A, Intron A) (13, 14), IFN-β (Avonex, Rebif, Betaseron) (15, 16), IFN-γ (Actimmune) (17), granulocyte colony-stimulating factor (Neupogen) (18), and granulocyte macrophage colony-stimulating factor (Leukine) (19, 20). The recommended dose is typically very low (often <1 mg/d) (21–23), as cytokines may exert biological activity in the subnanomolar concentration range (24). Various strategies have been proposed to develop cytokine products with improved therapeutic index. Protein PEGylation or Fc fusions may lead to prolonged circulation time in the bloodstream, allowing the administration of low doses of active payload (25, 26). In some implementations, cleavable polyethylene glycol polymers may be considered, yielding prodrugs that regain activity at later time points (27). Alternatively, tumor-homing antibody fusions have been developed, since the preferential concentration of cytokine payloads at the tumor site has been shown in preclinical models to potentiate therapeutic activity, helping spare normal tissues (28–34). Various antibody-cytokine fusions are currently being investigated in clinical trials for the treatment of cancer and of chronic inflammatory conditions (reviewed in refs. 2, 33, 35–37).Antibody-cytokine fusions display biological activity immediately after injection into patients, which may lead to unwanted toxicity and prevent escalation to therapeutically active dosage regimens (9, 22, 38). In the case of proinflammatory payloads (e.g., IL-2, IL-12, TNF-α), common side effects include hypotension, nausea, and vomiting, as well as flu-like symptoms (24, 39–42). These side effects typically disappear when the cytokine concentration drops below a critical threshold, thus providing a rationale for slow-infusion administration procedures (43). It would be highly desirable to generate antibody-cytokine fusion proteins with excellent tumor-targeting properties and with “activity on demand”— biological activity that is conditionally gained on antigen binding at the site of disease, helping spare normal tissues.Here we describe a fusion protein consisting of the F8 antibody specific to the alternatively spliced extra domain A (EDA) of fibronectin (44, 45) and of murine 4-1BBL, which did not exhibit cytokine activity in solution but could regain potent biological activity on antigen binding. The antigen (EDA+ fibronectin) is conserved from mouse to man (46), is virtually undetectable in normal adult tissues (with the exception of the placenta, endometrium, and some vessels in the ovaries), but is expressed in the majority of human malignancies (44, 45, 47, 48). 4-1BBL, a member of the TNF superfamily (49), is expressed on antigen-presenting cells (50, 51) and binds to its receptor, 4-1BB, which is up-regulated on activated cytotoxic T cells (52), activated dendritic cells (52), activated NK and NKT cells (53), and regulatory T cells (54). Signaling through 4-1BB on cytotoxic T cells protects them from activation-induced cell death and skews the cells toward a more memory-like phenotype (55, 56).We engineered nine formats of the F8-4-1BBL fusion protein, one of which exhibited superior performance in quantitative biodistribution studies and conditional gain of cytokine activity on antigen binding. The antigen-dependent reconstitution of the biological activity of the immunostimulatory payload represents an example of an antibody fusion protein with “activity on demand.” The fusion protein was potently active against different types of cancer without apparent toxicity at the doses used. The EDA of fibronectin is a particularly attractive antigen for cancer therapy in view of its high selectivity, stability, and abundant expression in most tumor types (44, 45, 47, 48).     

“You” speaks to me: Effects of generic-you in creating resonance between people and ideas

Creating resonance between people and ideas is a central goal of communication. Historically, attempts to understand the factors that promote resonance have focused on altering the content of a message. Here we identify an additional route to evoking resonance that is embedded in the structure of language: the generic use of the word “you” (e.g., “You can’t understand someone until you’ve walked a mile in their shoes”). Using crowd-sourced data from the Amazon Kindle application, we demonstrate that passages that people highlighted—collectively, over a quarter of a million times—were substantially more likely to contain generic-you compared to yoked passages that they did not highlight. We also demonstrate in four experiments (n = 1,900) that ideas expressed with generic-you increased resonance. These findings illustrate how a subtle shift in language establishes a powerful sense of connection between people and ideas.

Consider the feeling evoked by watching a gripping scene in a film, hearing a moving song, or coming across a quotation that seems to be written just for you. Experiencing resonance, a sense of connection, is a pervasive human experience. Prior research examining the processes that promote this experience suggests that altering a message to evoke emotion (1–7), highlighting its applicability to a person’s life (2, 6, 8–10), or appealing to a person’s beliefs (4, 8, 11) can all contribute to an idea’s resonance. Here we examine an additional route to cultivating this experience, which is grounded in a message’s form rather than its content: the use of a linguistic device that frames an idea as applying broadly.The ability to frame an idea as general rather than specific is a universal feature of language (12–15). One frequently used device is the generic usage of the pronoun “you” (15–17). Although “you” is often used to refer to a specific person or persons (e.g., “How did you get to work today?”), in many languages, it can also be used to refer to people in general (e.g., “You avoid rush hour if you can.”). This general use of “you” is comparable to the more formal “one,” but is used much more frequently (18).Research indicates that people often use “you” in this way to generalize from their own experiences. For example, a person reflecting on getting fired from their job might say, “It makes you feel betrayed” (18). Here, we propose that using “you” to refer to people in general has additional social implications, affecting whether an idea evokes resonance.Two features of the general usage of “you” (hereafter, “generic-you”) motivate this hypothesis. First, generic-you conveys that ideas are generalizable. Rather than expressing information that applies to a particular situation (e.g., “Leo broke your heart”), generic-you expresses information that is timeless and applies across contexts (e.g., “Eventually, you recover from heartbreak”; 18–23). Second, generic-you is expressed with the same word ("you") that is used in nongeneric contexts to refer to the addressee. Thus, even when “you” is used generically, the association to its specific meaning may further pull in the addressee, heightening resonance. Together, these features suggest that generic-you should promote the resonance of an idea. We tested this hypothesis across five preregistered studies (24–28), using a combination of crowd-sourced data and online experimental paradigms. Data, code, and materials are publicly available via the Open Science Framework (https://osf.io/6J2ZC/) (29). Study 1 used publicly available data from the Amazon Kindle application. Studies 2–5 were approved by the University of Michigan Health Sciences and Behavioral Sciences institutional review board (IRB) under HUM00172473 and deemed exempt from ongoing IRB review. All participants who participated in studies 2–5 provided informed consent via a checkbox presented through the online survey platform, Qualtrics.     

Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration

A transplanted stem cell’s engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell’s “pathotropism.” Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12–CXCR4 coupling. Alternatively, we chemically “mutated” CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a “designer” cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., “inflammo-attraction”).

A transplanted stem cell’s engagement with a pathologic niche is the first step in cell-mediated restoration of homeostasis to that region, whether by cell replacement, protection, gene delivery, milieu alteration, toxin neutralization, or remodeling (1–4). Not surprisingly, the more host terrain covered by the stem cells, the greater their impact. We and others found that a propensity for neural stem cells (NSCs) to home in vivo to acutely injured or actively degenerating central nervous system (CNS) regions—a property called “pathotropism” (1–12), now viewed as central to stem cell biology—is undergirded, at least in part, by the presence of chemokine receptors on the NSC surface, enabling them to follow concentration gradients of inflammatory cytokines constitutively elaborated by pathogenic processes and expressed by reactive astrocytes and injured vascular endothelium within the pathologic niche (5–9). This engagement of NSC receptors was first described for the prototypical chemokine receptor CXCR4 (C-X-C chemokine receptor type 4; also known as fusin or cluster of differentiation-184 [CD184]) and its unique natural cognate agonist ligand, the inflammatory chemokine CXCL12 (C-X-C motif chemokine ligand-12; also known as stromal cell-derived factor 1α [SDF-1α]) (5), but has since been described for many chemokine receptor-agonist pairings (6–9). Chemokine receptors belong to a superfamily that is characterized by seven transmembrane GDP-binding protein-coupled receptors (GPCRs) (13–21). In addition to their role in mediating inflammatory reactions and immune responses (22, 23), these receptors and their agonists are components of the regulatory axes for hematopoiesis and organogenesis in other systems (21, 24). Therefore, it is not surprising that binding of CXCL12 to CXCR4 mediates not only an inflammatory response, but also triggers within the NSC a series of intracellular processes associated with migration (as well as proliferation, differentiation, survival, and, during early brain development, proper neuronal lamination) (10).A tool directing therapeutic NSCs to where they are needed has long been sought in regenerative medicine (11, 12). While it was appealing to contemplate electively directing reparative NSCs to any desired area by emulating this chemoattractive property through the targeted injection of exogenous recombinant inflammatory cytokines, it ultimately seemed inadvisable to risk increasing toxicity in brains already characterized by excessive and usually inimical inflammation from neurotraumatic or neurodegenerative processes. However, the notion of engaging the homing function of these NSC-borne receptors without triggering that receptor’s undesirable downstream inflammatory signaling [particularly given that the NSCs themselves can exert a therapeutic antiinflammatory action in the diseased region (1, 2)] seemed a promising heretofore unexplored “workaround.”There had already been an impetus to examine the structure–function relationships of CXCR4, known to be the entry route into cells for HIV-1, in order to create CXCR4 antagonists that block viral infection (25–30). Antagonists of CXCR4 were also devised to forestall hematopoietic stem cells from homing to the bone marrow, hence prolonging their presence in the peripheral blood (31) to treat blood dyscrasias. An agonist, however, particularly one with discrete and selective actions, had not been contemplated. In other words, if CXCL12 could be stripped of its undesirable actions while preserving its tropic activity, an ideal chemoattractant would be derived.Based on the concept that CXCR4’s functions are conveyed by two distinct molecular “pockets”—one mediating binding (i.e., allowing a ligand to engage CXCR4) and the other mediating signaling (i.e., enabling a ligand, after binding, to trigger CXCR4-mediated intracellular cascades that promote not only inflammation but also migration) (13–18)—we performed chemical mutagenesis that should optimize binding while narrowing the spectrum of signaling. We created a simplified de novo peptide agonist of CXCR4 that contained a strong pure binding motif derived from CXCR4’s strongest ligand, viral macrophage inflammatory protein-II (vMIP-II) and linked it to a truncated signaling motif (only 8 amino acid residues) derived from the N terminus of native CXCL12 (19, 20). This synthetic dual-moiety CXCR4 agonist, which is devoid of a large portion of CXCL12’s native sequence (presumably responsible for undesired functions such as inflammation) not only elicited (with great specificity) more extensive and long-lasting human NSC (hNSC) migration and distribution than native CXCL12 (overcoming migratory barriers), but induced no host inflammation (or other adverse effects). Furthermore, because all of the amino acids in the binding motif were in a D-chirality, rendering the peptide resistant to enzymatic degradation, persistence of this benign synthetic agonist in vivo was prolonged. The hNSC’s gene ontology expression profile was predominantly reparative in contrast to inflammatory as promoted by native CXCL12. When coadministered with transplanted human induced pluripotent stem cell (hiPSC)-derived hNSCs (hiPSC derivatives are now known to have muted migration) in a mouse model of a prototypical neurodegenerative disease [the lethal neuropathic lysosomal storage disorder (LSD) Sandhoff disease (29), where hiPSC-hNSC migration is particularly limited], the synthetic agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cortex (including as electrophysiologically active cortical neurons), where their secreted cross-corrective enzyme could mediate a histological and functional therapeutic impact in a manner unachieved by transplanting hiPSC-derived cells alone.In introducing such a “designer” cytokine receptor agonist, we hope to offer proof-of-concept that stem cell-mediated treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., “inflammo-attraction”) to alter a niche and augment specific actions. Additionally, when agonists are strategically designed, the various functions of chemokine receptors (and likely other GCPRs) may be divorced. We demonstrate that such a strategy might be used safely and effectively to direct cells to needed regions and broaden their chimerism. We discuss the future implications and uses within the life sciences of such a chemical engineering approach.     

Atomic-scale evidence for highly selective electrocatalytic N−N coupling on metallic MoS2

Molybdenum sulfide (MoS₂) is the most widely studied transition-metal dichalcogenide (TMDs) and phase engineering can markedly improve its electrocatalytic activity. However, the selectivity toward desired products remains poorly explored, limiting its application in complex chemical reactions. Here we report how phase engineering of MoS₂ significantly improves the selectivity for nitrite reduction to nitrous oxide, a critical process in biological denitrification, using continuous-wave and pulsed electron paramagnetic resonance spectroscopy. We reveal that metallic 1T-MoS₂ has a protonation site with a pK_a of ∼5.5, where the proton is located ∼3.26 Å from redox-active Mo site. This protonation site is unique to 1T-MoS₂ and induces sequential proton−electron transfer which inhibits ammonium formation while promoting nitrous oxide production, as confirmed by the pH-dependent selectivity and deuterium kinetic isotope effect. This is atomic-scale evidence of phase-dependent selectivity on MoS₂, expanding the application of TMDs to selective electrocatalysis.

Transition-metal dichalcogenides (TMDs) have gained considerable attention in recent years due to their variable crystal phases, which allow for precise tuning of their electronic, optical, magnetic, and catalytic properties (1, 2). For example, molybdenum sulfide (MoS₂), which is one of the most extensively studied TMDs, exists as different polymorphs depending on the orientation of sulfur atoms around the molybdenum center. In octahedral coordination (1T phase), MoS₂ exhibits metallic behavior, whereas the material acts as a semiconductor in trigonal prismatic coordination (2H phase) (3–6). In addition to higher conductivity, 1T-MoS₂ has enlarged layer spacing and more electrochemical active sites (7, 8), making it a promising next-generation material for batteries (9, 10), memristors (11, 12), capacitors (13, 14), and numerous other energy-related applications (15–17).In the field of electrocatalysis, phase engineering has mainly been used to enhance catalytic activity. For instance, exchanging 2H-MoS₂ for 1T-MoS₂ results in a marked increase toward the hydrogen evolution reaction (18, 19). Considering the advantage of TMDs being able to control the atomic-scale structure, phase engineering may also open possibilities to control the selectivity of multielectron/proton reactions with multiple possible products, such as CO₂ reduction (20–23), denitrification (NO₃⁻/NO₂⁻ reduction) (24–26), and the electrosynthesis of functional molecules (27–30). Selectivity is a critical requirement for cascade catalysis, one-pot reaction systems, and multistep catalytic processes, and strategies to guide the complex chemical reaction network toward the desired end product are necessary (31, 32). However, to the best of our knowledge, no studies have attempted to exploit the advantages of phase-engineered materials for selective electrocatalysis.One effective approach to explore phase-engineered MoS₂ for selectivity control is to utilize the newly proposed concept of sequential proton−electron transfer (SPET) (off-diagonal pathways, Fig. 1A) (33, 34). In contrast to the extensively studied concerted proton−electron transfer (CPET) pathway, the energy landscape of sequential (decoupled) proton−electron transfer (SPET) pathways is pH-dependent (Fig. 1B). This leads to pH-dependent reaction rates (Fig. 1C), where the maximum reaction rate can be obtained at a pH close to the pK_a of the reaction intermediate (33, 34). This was recently observed experimentally for nitrite reduction to dinitrogen – an artificial analog of biological denitrification – on partially oxygenated molybdenum sulfide (oxo-MoS_x), and the record high selectivity toward dinitrogen was achieved by simple pH optimization (35). In contrast, this pH dependence was absent in the case of crystalline 2H-MoS₂, demonstrating that the SPET pathway is a unique property of oxo-MoS_x and is therefore probably phase-dependent. However, the origin of the SPET behavior on this material remains unclear. Therefore, elucidating the mechanism at the atomic level would help rationalize the relationship between selectivity and crystal phases, thus providing significant insight into the newly proposed SPET mechanism (33, 34) to enhance the selectivity of multistep electrochemical processes.Open in a separate windowFig. 1.Selectivity control of MoS₂ based on SPET theory. (A) Diagram showing the possible pathways for proton−electron transfer on MoS₂. In the blue pathway (CPET), protons and electrons are transferred in a single elementary step. In contrast, stepwise pathways (SPET) generate an intermediate whose charge depends on whether the electron or proton transfers first (red and black pathways, respectively). (B) Diagram showing the energetic landscape of SPET. The landscape depends on the relationship between the pK_a of the reaction intermediate and the solution pH. (C) Influence of pH on reaction selectivity. The rates of SPET reactions (red lines) show a pH dependence with a maximum corresponding to the pK_a of the intermediate. Therefore, the relative rate of one reaction over another can be tuned by changing the pH. In contrast, the rate of CPET reactions are pH-independent, and therefore, their relative rates are also constant with respect to pH.Here, we identified the atomic-scale origin of SPET-driven selectivity on MoS₂ using continuous-wave electron paramagnetic resonance (CW-EPR), Raman, and pulsed ¹H/²H electron−nuclear double-resonance (ENDOR) spectroscopy. Specifically, a proton located at the first coordination sphere (∼3.26 Å) of a redox-active Mo center was found to have a pK_a value matching that involved in the pH-dependent electrocatalytic selectivity and H/D kinetic isotope effect (KIE). The observed pH-dependent behavior is specific to 1T-MoS₂, as oxo-MoS_x was assigned to the 1T phase using high-resolution transmission electron microscopy (HRTEM), Raman- and X-ray photoelectron spectroscopy (XPS). These results not only provide atomic-scale evidence of SPET in heterogeneous catalysis, but also demonstrate how the phase engineering of TMDs can be used to enhance their electrocatalytic selectivity.     

Unveiling the “invisible” druggable conformations of GDP-bound inactive Ras

The prevalent view on whether Ras is druggable has gradually changed in the recent decade with the discovery of effective inhibitors binding to cryptic sites unseen in the native structures. Despite the promising advances, therapeutics development toward higher potency and specificity is challenged by the elusive nature of these binding pockets. Here we derive a conformational ensemble of guanosine diphosphate (GDP)-bound inactive Ras by integrating spin relaxation-validated atomistic simulation with NMR chemical shifts and residual dipolar couplings, which provides a quantitative delineation of the intrinsic dynamics up to the microsecond timescale. The experimentally informed ensemble unequivocally demonstrates the preformation of both surface-exposed and buried cryptic sites in Ras•GDP, advocating design of inhibition by targeting the transient druggable conformers that are invisible to conventional experimental methods. The viability of the ensemble-based rational design has been established by retrospective testing of the ability of the Ras•GDP ensemble to identify known ligands from decoys in virtual screening.

Situated in a central position of the complex intracellular signaling network, Ras proteins play critical roles in regulating cell growth, differentiation, migration and apoptosis through cycling between the guanosine diphosphate (GDP)-bound inactive and guanosine triphosphate (GTP)-bound active forms (1, 2). Aberrant signaling caused by oncogenic mutations in Ras that break this physiological balance can result in uncontrolled cell proliferation and ultimately the development of human malignancies (3, 4). Despite its well-established role in tumorigenesis and the extensive efforts to target this oncoprotein in past decades, clinically approved therapies remain unavailable. One obstacle to the development of anti-Ras drugs lies in the native structures of active and inactive Ras that lack apparently druggable pockets for high-affinity interactions with inhibitory compounds (5–7).Both the active and inactive forms of Ras, however, are inherently flexible, populating rare conformers distinct from the native structures and presenting alternative opportunities for drug discovery (8–11). For example, in GTP-bound active Ras, a major and minor state (termed states 2 and 1, respectively) coexist in solution and exchange on a millisecond timescale, with state 1 showing surface roughness unobserved in the major state (12–18). The direct visibility of state 1 in the one-dimensional ³¹P NMR spectra of active Ras largely facilitated its early discovery and characterization (12, 19). And the available mutants of H-Ras (e.g., T35A), or the homolog M-Ras, which predominantly assume the state 1 conformation, further promoted the atomic-resolution studies of its structure and internal dynamics, as well as the concomitant drug discovery efforts targeting this low-populated conformer (17, 18, 20).In comparison to the intensive studies on active Ras, research on the dynamics of GDP-bound inactive Ras has lagged far behind, presumably due to its high degree of spectral homogeneity with little sign of resonance splitting or exchange broadening at room temperature (21). The previously reported cryptic pockets for covalent and noncovalent inhibitors of Ras•GDP (22–24), which are unseen in the compound-free structure, nevertheless indicate that the inactive form is also structurally plastic. The recent relaxation-based NMR experiments carried out at low temperature successfully captured the intrinsic microsecond timescale motions in Ras•GDP, which map to regions that overlap with those rearranged on the binding of inhibitors (11). However, the structural information of the transiently formed excited state, in the form of chemical shifts, is not available from the relaxation measurements, owing to the fast exchange rate on the chemical shift timescale. Moreover, unlike the case of active Ras, there are no known mutations that can stabilize the excited state of Ras•GDP for investigations using conventional biophysical techniques. Thus far, the sparsely populated conformations of inactive Ras derived from its microsecond dynamics remain poorly understood, precluding structure-based rational drug discovery.To address these challenges, in this work we constructed a solution ensemble of Ras•GDP by integrating atomistic computer simulation with diverse NMR experimental parameters containing complementary information about the intrinsic protein motions on timescales from picoseconds to microseconds. This NMR-based ensemble well covers the slow dynamics as probed by spin relaxation and provides an atomic-resolution delineation of thermally accessible conformations, including those bearing surface or buried pockets similar to the cryptic pockets previously observed in the inhibitor-bound forms. The utility of the Ras•GDP ensemble in the development of inhibitors is demonstrated by ensemble-based virtual screening, which achieves an impressive level of enrichment of known binders.     

The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat

The HIV-1 gp41 N-heptad repeat (NHR) region of the prehairpin intermediate, which is transiently exposed during HIV-1 viral membrane fusion, is a validated clinical target in humans and is inhibited by the Food and Drug Administration (FDA)-approved drug enfuvirtide. However, vaccine candidates targeting the NHR have yielded only modest neutralization activities in animals; this inhibition has been largely restricted to tier-1 viruses, which are most sensitive to neutralization by sera from HIV-1–infected individuals. Here, we show that the neutralization activity of the well-characterized NHR-targeting antibody D5 is potentiated >5,000-fold in TZM-bl cells expressing FcγRI compared with those without, resulting in neutralization of many tier-2 viruses (which are less susceptible to neutralization by sera from HIV-1–infected individuals and are the target of current antibody-based vaccine efforts). Further, antisera from guinea pigs immunized with the NHR-based vaccine candidate (ccIZN36)₃ neutralized tier-2 viruses from multiple clades in an FcγRI-dependent manner. As FcγRI is expressed on macrophages and dendritic cells, which are present at mucosal surfaces and are implicated in the early establishment of HIV-1 infection following sexual transmission, these results may be important in the development of a prophylactic HIV-1 vaccine.

Membrane fusion between HIV-1 and host cells is mediated by the viral envelope glycoprotein (Env), a trimer consisting of the gp120 and gp41 subunits. Upon interaction with cellular receptors, Env undergoes a dramatic conformational change and forms the prehairpin intermediate (PHI) (1–3), in which the fusion peptide region at the amino terminus of gp41 inserts into the cell membrane. In the PHI, the N-heptad repeat (NHR) region of gp41 is exposed and forms a stable, three-stranded α-helical coiled coil. Subsequently, the PHI resolves when the NHR and the C-heptad repeat (CHR) regions of gp41 associate to form a trimer-of-hairpins structure that brings the viral and cell membranes into proximity, facilitating membrane fusion (Fig. 1).Open in a separate windowFig. 1.HIV-1 membrane fusion. The surface protein of the HIV-1 envelope is composed of the gp120 and gp41 subunits. After Env binds to cell-surface receptors, gp41 inserts into the host cell membrane and undergoes a conformational change to form the prehairpin intermediate. The N-heptad repeat (orange) region of gp41 is exposed in the PHI and forms a three-stranded coiled coil. To complete viral fusion, the PHI resolves to a trimer-of-hairpins structure in which the C-heptad repeat (blue) adopts a helical conformation and binds the NHR region. Fusion inhibitors such as enfuvirtide bind the NHR, preventing viral fusion by inhibiting formation of the trimer of hairpins (1–3). The membrane-proximal external region (red) is located adjacent to the transmembrane (TM) region of gp41.The NHR region of the PHI is a validated therapeutic target in humans: the Food and Drug Administration (FDA)-approved drug enfuvirtide binds the NHR and inhibits viral entry into cells (4, 5). Various versions of the three-stranded coiled coil formed by the NHR have been created and used as vaccine candidates in animals (6–10). The neutralization potencies of these antisera, as well as those of anti-NHR monoclonal antibodies (mAbs) (11–15), are modest and mostly limited to HIV-1 isolates that are highly sensitive to antibody-mediated neutralization [commonly referred to as tier-1 viruses (16)]. These results have led to skepticism about the PHI as a vaccine target.Earlier studies showed that the neutralization activities of mAbs that bound another region of gp41, the membrane-proximal external region (MPER) (Fig. 1), were enhanced as much as 5,000-fold in cells expressing FcγRI (CD64) (17, 18), an integral membrane protein that binds the Fc portion of immunoglobulin G (IgG) molecules with high (nanomolar) affinity (19, 20). This effect was not attributed to phagocytosis and occurred when the cells were preincubated with antibody and washed before adding virus (17, 18). Since the MPER is a partially cryptic epitope that is not fully exposed until after Env engages with cellular receptors (21, 22), these results suggest that by binding the Fc region, FcγRI provides a local concentration advantage for MPER mAbs at the cell surface that enhances viral neutralization (17, 18). While not expressed on T cells, FcγRI is expressed on macrophages and dendritic cells (23), which are present at mucosal surfaces and are implicated in sexual HIV-1 transmission and the early establishment of HIV-1 infection (22–34).Here we investigated whether FcγRI expression also potentiates the neutralizing activity of antibodies targeting the NHR, since that region, like the MPER, is preferentially exposed during viral fusion. We found that D5, a well-characterized anti-NHR mAb (11, 12), inhibits HIV-1 infection ∼5,000-fold more potently in TZM-bl cells expressing FcγRI (TZM-bl/FcγRI cells) than in TZM-bl cells that do not. Further, while antisera from guinea pigs immunized with (ccIZN36)₃, an NHR-based vaccine candidate (7), displayed weak neutralizing activity in TZM-bl cells, they exhibited enhanced neutralization in TZM-bl/FcγRI cells, including against some tier-2 HIV-1 isolates that are more resistant to antibody-mediated neutralization (16) and that serve as benchmarks for antibody-based vaccine efforts. These results indicate that FcγRI can play an important role in neutralization by antibodies that target the PHI. Since these receptors are expressed on cells prevalent at mucosal surfaces thought to be important for sexual HIV-1 transmission, our results motivate vaccine strategies that harness this potentiating effect.     

From the Cover: A Middle Eocene lowland humid subtropical “Shangri-La” ecosystem in central Tibet

Tibet’s ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This “Shangri-La”–like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

The Tibetan Plateau, once thought of as entirely the product of the India–Eurasia collision, is known to have had significant complex relief before the arrival of India early in the Paleogene (1–3). This large region, spanning ∼2.5 million km², is an amalgam of tectonic terranes that impacted Asia long before India’s arrival (4, 5), with each accretion contributing orographic heterogeneity that likely impacted climate in complex ways. During the Paleogene, the Tibetan landscape comprised a high (>4 km) Gangdese mountain range along the southern margin of the Lhasa terrane (2), against which the Himalaya would later rise (6), and a Tanghula upland on the more northerly Qiangtang terrane (7). Separating the Lhasa and Qiangtang blocks is the east–west trending Banggong-Nujiang Suture (BNS), which today hosts several sedimentary basins (e.g., Bangor, Nyima, and Lunpola) where >4 km of Cenozoic sediments have accumulated (8). Although these sediments record the climatic and biotic evolution of central Tibet, their remoteness means fossil collections have been hitherto limited. Recently, we discovered a highly diverse fossil assemblage in the Bangor Basin. These fossils characterize a luxuriant seasonally wet and warm Shangri-La forest that once occupied a deep central Tibetan valley along the BNS, and provide a unique opportunity for understanding the evolutionary history of Asian biodiversity, as well as for quantifying the paleoenvironment of central Tibet.^*Details of the topographic evolution of Tibet are still unclear despite decades of investigation (4, 5). Isotopic compositions of carbonates recovered from sediments in some parts of central Tibet have been interpreted in terms of high (>4 km) Paleogene elevations and aridity (9, 10), but those same successions have yielded isolated mammal (11), fish (12), plant (13–18), and biomarker remains (19) more indicative of a low (≤3-km) humid environment, but how low is poorly quantified. Given the complex assembly of Tibet, it is difficult to explain how a plateau might have formed so early and then remained as a surface of low relief during subsequent compression from India (20). Recent evidence from a climate model-mediated interpretation of palm fossils constrains the BNS elevation to below 2.3 km in the Late Paleogene (16), but more precise paleoelevation estimates are required. Further fossil discoveries, especially from earlier in the BNS sedimentary records, would document better the evolution of the Tibetan biota, as well as informing our understanding of the elevation and climate in an area that now occupies the center of the Tibetan Plateau.Our work shows that the BNS hosted a diverse subtropical ecosystem at ∼47 Ma, and this means the area must have been both low and humid. The diversity of the fossil flora allows us to 1) document floristic links to other parts of the Northern Hemisphere, 2) characterize the prevailing paleoclimate, and 3) quantify the elevation at which the vegetation grew. We propose that the “high and dry” central Tibet inferred from some isotope paleoaltimetry (9, 10) reflects a “phantom” elevated paleosurface (20) because fractionation over the bounding mountains allowed only isotopically light moist air to enter the valley, giving a false indication of a high elevation (21).     

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.     

From the Cover: Toward net-zero sustainable aviation fuel with wet waste–derived volatile fatty acids

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C₂ to C₈ volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste–derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM “Fast Track” qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste–derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for “Fast Track.” Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.

Over 21 billion gallons of jet fuel are consumed in the United States annually, with demand expected to double by 2050 (1). The aviation sector accounts for 2.5% of global greenhouse gas emissions, with airlines committing to reduce their carbon footprint by 50% before 2050 (2, 3). Sustainable aviation fuels (SAF) comprise a significant portion of the aviation sector’s strategy for CO₂ reductions given the limited near-term prospects for electrification (3–5). In addition, the low aromatic content of current SAF routes has been shown to reduce soot formation and aviation-related aerosol emissions by 50 to 70% (2, 6, 7), which can significantly impact the net global warming potential. Soot is the primary nucleator of aviation-induced contrails (8), which have a larger effective radiative forcing (57.4 mW/m²) than aviation-emitted CO₂ alone (34.3 mW/m²) (3).Commercial SAF production in the United States currently relies on the hydrotreating of esters and fatty acids (HEFA) using virgin vegetable oils as well as waste fats, oils, and greases. These feedstocks also serve the renewable diesel market, which in 2018, produced ∼300 million gallons of HEFA diesel compared to ∼2 million gallons of HEFA SAF (1). Global HEFA capacity is estimated at 1.1 billion gallons per year (BGPY) in 2017 (9). HEFA SAF competes with demand for HEFA diesel, with US fossil diesel consumption estimated at ∼47 BGPY (10). Producing HEFA SAF requires an additional catalytic cracking step to convert predominantly C₁₆ and C₁₈ long chain fatty acids into C₈ to C₁₈ hydrocarbons suitable for jet fuel. This consumes additional hydrogen and lowers the jet and diesel fuel yield, making HEFA SAF more expensive to produce than HEFA diesel (11). California’s Low Carbon Fuel Standard (LCFS) has provided significant economic incentive for producing HEFA from low carbon intensity feedstocks (12), with petroleum companies continuing to retrofit existing refineries (13). Although this expansion will significantly increase biofuel production, the US availability of fats, oils, and greases is capped at ∼1.7 BGPY of jet fuel equivalent (14, 15). As such, efforts are needed to develop alternative feedstocks and conversion routes for SAF that avoid direct competition with food resources.Wet waste is an underutilized feedstock in the United States, with an energy content equivalent to 10.5 BGPY of jet fuel equivalent (assumed 130.4 MJ/gallon). Wet waste includes food waste (2.5 BPGY), animal manure (4.4 BGPY), wastewater sludge (1.9 BPGY), and the abovementioned waste fats, oils, and grease (1.7 BGPY) (14, 15). While waste lipid feedstocks may be best suited for HEFA refining, valorization strategies are needed for the remaining wet waste feedstocks. Diverting food waste from landfills is of particular note for reducing greenhouse gas emissions, as landfilling one dry ton of food waste has been estimated to release as much as 1.8 tons of CO₂ equivalents, assuming landfill methane is collected and recovered for electricity generation (16, 17). Globally, food waste accounts for 6% of greenhouse emissions (18). The high moisture content of wet waste restricts the use of conventional thermochemical conversion approaches (e.g., pyrolysis and gasification) used to produce liquid biofuels from terrestrial biomass, directing technology development efforts toward hydrothermal liquefaction, biological conversion, and hybrid processes (19).Currently, anaerobic digestion to produce biogas is the leading technology to recover energy from wet waste (20). The high moisture content of wet waste limits its transport and necessitates local processing, with the majority of US anaerobic digestion facilities located near population-dense areas and airports (21). Biogas purification provides a route to pipeline quality renewable natural gas compatible with existing infrastructure. Life cycle analysis has shown that negative carbon intensity can be achieved when producing renewable natural gas from municipal solid waste (−23 g CO₂eq/MJ) and dairy waste (−276 g CO₂eq/MJ), providing a significant economic driver under the LCFS (12). While renewable natural gas targets an enormous US market (∼246 BGPY of jet fuel equivalent) (10), producing liquid hydrocarbon fuels from wet waste offers the potential to address the challenge of decarbonizing the aviation sector.Anaerobic digestion of wet waste can be arrested prior to methanogenesis to generate both short chain (C₂ to C₅) and medium chain length (C₆ to C₈) carboxylic acids as precursors for biofuels and biobased chemicals (14, 22–27), hereon collectively referred to as volatile fatty acids (VFAs). VFA production by arrested methanogenesis offers the potential to utilize existing biogas infrastructure and a wide variety of wet waste feedstocks (14, 22, 28) with ongoing research and development working to increase VFA titers, rates, and yields by tailoring feedstock composition, microbial consortia, fermentation parameters, and online separation technologies (14, 22, 29–31). Currently, C₂ to C₅ carboxylic acids are primarily produced from the oxidation of petroleum derivatives, while C₆ and C₈ carboxylic acids are primarily derived from coconut and palm oil (29). Propionic acid (C₃) and butyric acid (C₄) address chemical market volumes on the order of 0.1 to 0.2 BGPY (29), while medium chain length carboxylic acids target smaller specialty markets. Given the availability of wet waste and potential saturation of biobased chemical markets in the long term, VFAs provide a potential target intermediate for catalytic upgrading into low carbon intensity biofuel (23, 25, 26, 32–35).VFAs can be catalytically upgraded to SAF through carbon coupling and deoxygenation chemistries. Depending on their chain length, VFAs can be converted into normal paraffins identical to those found in petroleum or undergo an additional carbon coupling step to generate isoparaffin, cycloparaffin, and aromatic hydrocarbons with molecular structures distinct from fossil jet (Fig. 1).Open in a separate windowFig. 1.Overview scheme of the major oxygenate and hydrocarbon molecules produced when converting wet waste VFA into Fast Track VFA-SAF that is composed of normal paraffin-rich hydrocarbons (Top Right) and Aldol Condensation VFA-SAF composed of isoparaffin-rich hydrocarbons (Bottom Right).Ketonization is the first unit operation to elongate the carbon backbone of VFAs (14, 22). Ketonization reacts two VFAs to produce a single ketone that is one carbon shorter than the sum of both acids and removes oxygen in the form of water and carbon dioxide (36, 37). Ketonization of acetic acid to acetone has been commercialized (37), with longer chain acids actively researched for biofuel and biochemical applications. Following ketonization, ketones ≥C₈ can undergo direct hydrodeoxygenation (Fig. 1, Top) to produce normal paraffin-rich hydrocarbons. In comparison, ketones ≤C₇ require a second carbon coupling step prior to hydrodeoxygenation to fall within the C₈ to C₁₈ range of jet fuel (Fig. 1, Bottom). Ketone carbon coupling can take place by various pathways including aldol condensation chemistry (25) as well as ketone reduction to alcohols for further dehydration and oligomerization (32, 34). Aldol condensation of central ketones is an emerging bench-scale chemistry that can generate structurally unique isoparaffins (38) with significantly lower freezing points for jet fuel applications due to the high degree of branching as well as reduce the intrinsic sooting tendency relative to aromatic hydrocarbons by over twofold (25).Normal paraffins produced from VFAs (Fig. 1, Top) can provide fungible hydrocarbons identical to those in petroleum that offer a near-term path to SAF qualification and market entry. In the United States, new SAF conversion routes must complete a rigorous qualification process to ensure fuel safety and operability overseen by ASTM International, the Federal Aviation Administration, and aviation original equipment manufacturers (OEMs). There are currently seven ASTM-approved routes for SAF that are derived from Fischer–Tropsch processing of syngas, the abovementioned esters and fatty acids, farnesene, ethanol, isobutanol, and algal hydrocarbons (39). Further details summarizing current ASTM-qualified routes to SAF can be found in SI Appendix, Table S1. Historically, ASTM qualification can require jet fuel volumes on order of over 100,000 gallons in order to pass a four-tiered screening process and two OEM review stage gates that may take place over a period of 3 to 7 y (40). To help reduce this barrier, in January 2020, ASTM approved a new “Fast Track” qualification process for SAF routes that produce hydrocarbons structurally comparable to those in petroleum jet with a 10 vol% blend limit (41). “Fast Track” eliminates two tiers of testing and facilitates approval with under 1,000 gallons of fuel and within the timeframe of 1 to 2 y (42).In contrast, isoparaffins derived from aldol condensation can offer complementary fuel properties to increase the renewable blend content of VFA-SAF blends, but the unique chemical structures would not qualify for “Fast Track” approval. To accelerate the approval of SAF routes that produce molecules distinct from petroleum jet, small-volume fuel tests and predictive tools are being developed for the most critical bulk properties, which screen for potentially deleterious engine operability effects (i.e., lean blowout, cold ignition, and altitude relight) (43). These tests, referred to as Tier α and β prescreening (44), evaluate SAF candidates for established ASTM D7566 properties, as well as novel properties observed to be important through the National Jet Fuels Combustion Program (SI Appendix, Table S2) (43). New properties include surface tension and derived cetane number (CN), which impact ignition and lean blowout propensity, respectively. At less than one mL of test volume, Tier α can utilize gas chromatograph (GC) and GCxGC method data to predict all critical properties. With between 50 and 150 mL of neat material (depending on the CN measurement method used), Tier β test methods can measure the critical unblended operability properties. In terms of emissions, low-volume sooting tendency measurement methods have been developed that require <1 mL of fuel versus the 10 mL required to measure smoke point (45, 46). Combined, these new methods allow for rapid evaluation of developing SAF conversion routes.To advance the technology and fuel readiness level of VFA-SAF, this work evaluates the production of drop-in normal paraffins and structurally unique isoparaffins from food waste–derived VFAs. First, VFAs were biologically produced from food waste and recovered neat by an industry partner, Earth Energy Renewables. A simplified kinetic model was then developed for mixed VFA ketonization to determine the ketone carbon chain length distribution suitable for SAF production by each conversion route, with model results compared to experiments with biogenic VFAs. VFA ketonization was assessed for >100 h of continuous time-on-stream (TOS), with trace impurities characterized within the incoming biogenic VFA feed. Catalyst regeneration was evaluated for coke and impurity removal, as well as to compare fresh and regenerated catalyst activity. Following VFA ketonization, ≥C₈ ketones were processed by direct hydrodeoxygenation to generate predominantly normal paraffins suitable for 10% blend testing for ASTM Fast Track, hereon referred to as “Fast Track VFA-SAF.” In parallel, VFA-derived ketones ≤C₇ were processed via aldol condensation and hydrodeoxygenation to produce predominantly isoparaffin hydrocarbons for Tier α and Tier β prescreening, hereon referred to as “Aldol Condensation VFA-SAF.” Higher blends with both VFA-SAF fractions were examined to increase the renewable carbon content and reduce soot formation while still meeting fuel property specifications. Lastly, techno-economic and life cycle analysis was performed to evaluate the sensitivity of catalytic process parameters on VFA-SAF production costs as well as potential greenhouse gas reductions relative to fossil jet.     

Superelastic oxide micropillars enabled by surface tension–modulated 90° domain switching with excellent fatigue resistance

Superelastic materials capable of recovering large nonlinear strains are ideal for a variety of applications in morphing structures, reconfigurable systems, and robots. However, making oxide materials superelastic has been a long-standing challenge due to their intrinsic brittleness. Here, we fabricate ferroelectric BaTiO₃ (BTO) micropillars that not only are superelastic but also possess excellent fatigue resistance, lasting over 1 million cycles without accumulating residual strains or noticeable variation in stress–strain curves. Phase field simulations reveal that the large recoverable strains of BTO micropillars arise from surface tension–modulated 90° domain switching and thus are size dependent, while the small energy barrier and ultralow energy dissipation are responsible for their unprecedented cyclic stability among superelastic materials. This work demonstrates a general strategy to realize superelastic and fatigue-resistant domain switching in ferroelectric oxides for many potential applications.

Superelastic materials are capable of recovering large amount of nonlinear “plastic” strains, way beyond their linear elastic regimes (1–4). They are ideal for a variety of applications from morphing structures, reconfigurable systems, to robots (5–8). The effects have traditionally been associated with macroscopically compliant/ductile rubbers (2) or microscopically phase-transforming shape memory alloys (SMAs) (7–11). The only macroscopically brittle oxide recently discovered to be superelastic is ZrO₂-based micropillars or particles (12–20), which is realized via austenite-martensite phase transformation similar to SMAs. Although ultimate strengths approaching the theoretical limit have been demonstrated in nanoscale samples (21, 22), long fatigue life is elusive, which is arguably more important for most applications. As a matter of fact, poor fatigue life has been a long-standing challenge for oxide ceramics in general (23, 24). Even for ductile SMAs that enjoy excellent fatigue life, irrecoverable residual strains gradually accumulate over cycling, leading to substantial variations in stress–strain curves at different cycles (9, 10, 25). We overcome these difficulties by reporting superelastic barium titanate (BaTiO₃ [BTO]) micropillars enabled by surface tension–modulated 90° domain switching, which exhibit excellent fatigue resistance, while bulk BTO crystals or ceramics are rather brittle. The demonstration of over one million cycles of loading and unloading without accumulating residual strains or noticeable variation in stress–strain curves is unprecedented among superelastic materials.BTO is a ferroelectric oxide exhibiting modest piezoelectric strains around 0.1 to 0.2% (26) and fracture toughness of ∼1 MPa ⋅ m^1/2, and thus it is quite brittle (27). Considerable research efforts have been devoted to enhancing its electric field–induced strain via 90° ferroelectric domain switching (28–30). However, the process is often irreversible, and external mechanisms such as restoring force (28, 29) and internal mechanisms such as defect pinning (30) have to be invoked to make the electrostrain recoverable. Nevertheless, it hints at the possibility of BTO being made superelastic by taking advantage of the stress-induced 90° domain switching (6). Earlier works suggest that surface tension induces an in-plane compressive stress that favors the axial polarization in one-dimensional ferroelectrics at small size (31, 32), which may provide the necessary restoring mechanism for the stress-switched domains. Thus, if a compressive axial force is applied, reversible domain switching may occur during unloading, leading to superelasticity. To verify this hypothesis, we fabricated single-crystalline BTO micropillars from [001]-oriented bulk crystals (SI Appendix, Fig. S1A) via focused ion beam (FIB), as detailed in Materials and Methods and SI Appendix, Fig. S1B. The diameters (Φ) of the micropillars range from 0.5 μm to 5 μm, with their height to diameter ratio fixed at 3. No visible defects can be seen from the scanning electron microscopy (SEM) images of these micropillars shown in Fig. 1 A–D, and their surfaces appear to be quite smooth, suggesting that no apparent damages are induced by FIB.Open in a separate windowFig. 1.Superelastic BTO micropillars below a critical size. (A–D) SEM images of the micropillars with Φ = 5, 3, 2, and 0.5 μm. (E–G) The first and second cycles of stress–strain curves for BTO micropillars with Φ = 5, 2, and 0.5 μm. (H) S_r/S_max and ΔW/W_max during the first cycle for BTO micropillars of different diameters. Here, S_r and S_max denote the residual strain and the maximum strain (SI Appendix, Fig. S6A), while ΔW and W_max are energy dissipated and stored in the first cycle, respectively (SI Appendix, Fig. S6F).     

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.