Nitric oxide integrated polyethylenimine-based tri-block copolymer for efficient antibacterial activity

The work demonstrated a successful synthesis of nitric oxide (NO)-releasing material and its antibacterial effect on Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). The polymeric support composed of thermosensitive Pluronic F68 having good biocompatibility and branched polyethylenimine (BPEI) housed N-diazeniumdiolates (NONOates) which could store and release NO under appropriate physiological condition. The developed F68–BPEI–NONOates releases a sufficient amount of NO under physiological condition to elicit effective killing of E. coli, S. aureus and MRSA. The antibacterial ability of the released NO was compared to untreated control or unmodified F68 polymer by using confocal microscopy; F68–BPEI–NONOates demonstrated excellent antibacterial activity with in vitro low cytotoxicity. TEM investigation also revealed the destruction of bacteria membrane caused by NO. The effectiveness of F68–BPEI–NONOates against resistant strains such as MRSA provides a very simple but highly efficient strategy to combat drug-resistant bacterial infections.     

Development of Virtual Metrology Using Plasma Information Variables to Predict Si Etch Profile Processed by SF6/O2/Ar Capacitively Coupled Plasma

In the semiconductor etch process, as the critical dimension (CD) decreases and the difficulty of the process control increases, in-situ and real-time etch profile monitoring becomes important. It leads to the development of virtual metrology (VM) technology, one of the measurement and inspection (MI) technology that predicts the etch profile during the process. Recently, VM to predict the etch depth using plasma information (PI) variables and the etch process data based on the statistical regression method had been developed and demonstrated high performance. In this study, VM using PI variables, named PI-VM, was extended to monitor the etch profile and investigated the role of PI variables and features of PI-VM. PI variables are obtained through analysis on optical emission spectrum data. The features in PI-VM are investigated in terms of plasma physics and etch kinetics. The PI-VM is developed to monitor the etch depth, bowing CD, etch depth times bowing CD (rectangular model), and etch area model (non-rectangular model). PI-VM for etch depth and bowing CD showed high prediction accuracy of R-square value (R²) 0.8 or higher. The rectangular and non-rectangular etch area model PI-VM showed prediction accuracy R² of 0.78 and 0.49, respectively. The first trial of virtual metrology to monitor the etch profile will contribute to the development of the etch profile control technology.     

Systematic determination of absolute absorption cross-section of individual carbon nanotubes

Optical absorption is the most fundamental optical property characterizing light–matter interactions in materials and can be most readily compared with theoretical predictions. However, determination of optical absorption cross-section of individual nanostructures is experimentally challenging due to the small extinction signal using conventional transmission measurements. Recently, dramatic increase of optical contrast from individual carbon nanotubes has been successfully achieved with a polarization-based homodyne microscope, where the scattered light wave from the nanostructure interferes with the optimized reference signal (the reflected/transmitted light). Here we demonstrate high-sensitivity absorption spectroscopy for individual single-walled carbon nanotubes by combining the polarization-based homodyne technique with broadband supercontinuum excitation in transmission configuration. To our knowledge, this is the first time that high-throughput and quantitative determination of nanotube absorption cross-section over broad spectral range at the single-tube level was performed for more than 50 individual chirality-defined single-walled nanotubes. Our data reveal chirality-dependent behaviors of exciton resonances in carbon nanotubes, where the exciton oscillator strength exhibits a universal scaling law with the nanotube diameter and the transition order. The exciton linewidth (characterizing the exciton lifetime) varies strongly in different nanotubes, and on average it increases linearly with the transition energy. In addition, we establish an empirical formula by extrapolating our data to predict the absorption cross-section spectrum for any given nanotube. The quantitative information of absorption cross-section in a broad spectral range and all nanotube species not only provides new insight into the unique photophysics in one-dimensional carbon nanotubes, but also enables absolute determination of optical quantum efficiencies in important photoluminescence and photovoltaic processes.Single-walled carbon nanotubes (SWNTs), a model one-dimensional nanomaterial system, constitute a rich family of structures (1). Each single-walled nanotube structure, uniquely defined by the chiral index (n,m), exhibits distinct electrical and optical properties (2–5). Quantitative information of SWNT absorption cross-section is highly desirable for understanding nanotube electronic structures, for evaluating quantum efficiency of nanotube photoluminescence (5, 6) and photocurrent (7–9), and for investigating the unique many-body effects in 1D systems (10–16). Despite its obvious importance, reliable experimental determination of nanotube absorption cross-section at the single-tube level is still challenging (17). Previous absorption measurements on ensemble nanotube samples only provide averaged behavior (18–20). Recent absorption studies of individual nanotubes, suffering from small absorption signals and/or slow laser-frequency scanning, cannot determine the absolute absorption cross-section and are limited in achievable spectral range (15, 21–23).We demonstrate here a high-sensitivity polarization-based homodyne method to measure nanotube absorption spectra. By manipulating the light polarization, we enhanced the nanotube-induced transmission contrast, ΔI/I, by two orders of magnitude, and this enhanced transmission contrast can be quantitatively related to nanotube absorption cross-section along and perpendicular to the nanotube axis. Using this polarization control together with supercontinuum laser source, we realized high-throughput and broadband absorption measurements at the single-tube level; combined with electron diffraction technique on the same tube, it enables absolute determination of absorption cross-sections of individual chirality-defined nanotubes, to our knowledge for the first time. We obtained quantitative absorption spectra of over 50 SWNTs of different chiralities, and established a phenomenological formula for absorption cross-sections of different nanotubes. The chirality-dependent nanotube absorption spectra reveal unique 1D photophysics in nanotubes, including a universal scaling behavior of exciton oscillator strength and of exciton resonance linewidth.     

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer’s disease mice

Alzheimer’s disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disease with underlying pathologies that extend well beyond the widely recognized accumulation of amyloid beta (Aβ). Many studies have demonstrated that memory impairment in AD is driven by the interaction of various pathologic processes, such as cell death (1), impaired synapse plasticity (2), neurogenesis loss (3), autophagy dysfunction (4), vascular abnormalities (5), blood–brain barrier (BBB) damage (6), and systemic inflammation (7). Thus, effective drug development for this disorder must focus on therapeutic strategies that target the complex and multiple neuropathological features in AD.We and others have previously reported that the activity of several sphingolipid-metabolizing enzymes, especially acid sphingomyelinase (ASM), which is encoded by the SMPD1 gene, is abnormally expressed in AD patients and mouse models (8–10). The primary role of ASM is to catalyze the conversion of sphingomyelin, a major component of membranes, into ceramide and phosphocholine (11). The increased ASM activity in the blood and brain of AD mice contributes to various pathological features, including cell apoptosis (12), defective autophagy (8), neurogenesis loss (13), BBB leakage (14), and inflammation (15, 16), suggesting that ASM inhibition could be an important therapeutic target that addresses the neuropathological features of AD (17). Although some studies have previously identified direct or indirect functional inhibitors (17–20) of ASM, these inhibitors have lacked specificity, leading to the potential for off-target effects and unclear potential mechanisms of action in AD. Therefore, there is an important need to develop new compounds that block ASM activity by direct interaction with the enzyme.Here, we identify KARI 201 as a direct, selective, and competitive ASM inhibitor with excellent brain distribution and druggability. Interestingly, we also found an unexpected role of KARI 201 as an agonist of growth hormone secretagogue receptor 1α (GHSR1α, also known as the ghrelin receptor) via GPCR (G protein–coupled receptor) screening based on RNA-sequencing (RNA-seq) analysis in KARI 201–treated AD mice. This activity is critical for hippocampal synaptic physiology and may impact neuropathological features in AD as well (21–23). The dual action in neurons of KARI 201 as a direct ASM inhibitor and GHSR1α agonist led to outstanding, synergetic therapeutic effects in AD mouse models on neuropathological features involving learning and memory impairment. Therefore, our data highlight the possibility of clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.     

A ratiometric fluorescence probe for the selective detection of H2S in serum using a pyrene-DPA–Cd2+ complex

A ratiometric and selective hydrogen sulfide (H₂S) detection probe was proposed based on the pyrene-DPA–Cd²⁺ complex through the metal ion displacement approach (MDA) mechanism. While most MDA-based fluorescence probes with paramagnetic Cu²⁺ have focused on the development of a simple turn-on sensor using the broad spectral range of fluorescence enhancement, this ratiometric probe exhibited unchanged monomer emission as a built-in internal reference with an increase in excimer emission with added H₂S. The demonstrated probe showed a rapid response (within 1 min) and a high sensitivity, with 70 nM as the limit of detection. The selectivity for H₂S over cysteine, homocysteine and glutathione was confirmed, and reliable fluorescence enhancement, which could be monitored by the naked eye, was observed upon irradiation with handheld UV light. In addition, this detection system was successfully applied to detect H₂S in human serum without interference from biological molecules.

The pyrene-DPA–Cd²⁺ complex is demonstrated as a ratiometric fluorescence probe for selective hydrogen sulfide detection in serum based on a metal displacement approach.