Insights into the SiO2 Stress Effect on the Electrochemical Performance of Si anode.

Silicon (Si) is regarded as the most potential anode material for next-generation lithium-ion batteries (LIBs). However, huge volume expansion hinders its commercial application. Here, a yolk-shell structural nitrogen-doped carbon coated Si@SiO2 is prepared by SiO2 template and HF etching method. The as-prepared composite exhibits superior cycling stability with a high reversible capacity of 577 mA h g-1 at 1 A g-1 after 1000 cycles. The stress effect of SiO2 on stabilizing the electrochemical performance of Si anode is systematically investigated for the first time. In situ thickness measurement reveals that the volume expansion thickness of Si@SiO2 upon charge-discharge is obviously smaller than Si, demonstrating the electrode expansion can be effectively inhibited to improve the cyclability. The density functional theory (DFT) calculation further demonstrates the moderate young's modulus and enhanced hardness after SiO2 coating contribute significantly to the mechanical reinforcement of overall Si@SiO2@void@NC composite. Various post-cycling electrode analyses also address the positive effects of inner stress from the Si core on effectively relieving the damage to electrode structure, facilitating the formation of a more stable inorganic-rich solid electrolyte interphase (SEI) layer. This study provides new insights for mechanical stability and excellent electrochemical performance of Si-based anode materials.

Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors.

A series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of P1, P1 prime and P2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. 14c demonstrated excellent in-vitro potency (FXIa IC50: 15 nM, 2 x aPTT: 6.8 µM) and good in-vivo efficacy (prolonged in-vivo aPTT by more than 1-fold but not PT). Moreover, the pharmacokinetics property of 14c were evaluated following intravenous administration in rats, which indicated that 14c probably will be a clinical candidate for intravenous administration.

A density functional theory study on the mechanism of toluene from dimethylcyclopentane catalyzed by the [GaH]2+ active site of Ga-ZSM-5.

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

Characterization of a small molecule inhibitor of the NLRP3 inflammasome and its potential use for acute lung injury.

Accumulating data support the key roles of the NLRP3 inflammasome, an essential component of the innate immune system, in human pathophysiology. As an emerging drug target and a potential biomarker for human diseases, small molecule inhibitors of the NLRP3 inflammasome have been actively pursued. Our recent studies identified a small molecule, MS-II-124, as a potent NLRP3 inhibitor and potential imaging probe. In this report, MS-II-124 was further characterized by an unbiased and comprehensive analysis through Eurofins BioMAP Diversity PLUS panel that contains 12 human primary cell-based systems. The analysis revealed promising activities of MS-II-124 on inflammation and immune functions, further supporting the roles of the NLRP3 inflammasome in these model systems. Further studies of MS-II-124 in mouse model of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and NLRP3 knockout mice demonstrated its target engagement, efficacy to suppress inflammatory cytokines and infiltration of immune cells in the lung tissues. In summary, the results support the therapeutic potential of MS-II-124 as a NLRP3 inhibitor and warrant future studies of this compound and its analogs to develop therapeutics for ALI/ARDS.

Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability.

Astrocyte aerobic glycolysis provides vital trophic support for central nervous system neurons. However, whether and how astrocytic metabolic dysregulation contributes to neuronal dysfunction in intellectual disability (ID) remain unclear. Here, we demonstrate a causal role for an ID-associated SNX27 mutation (R198W) in cognitive deficits involving reshaping astrocytic metabolism. We generated SNX27R196W (equivalent to human R198W) knock-in mice and found that they displayed deficits in synaptic function and learning behaviors. SNX27R196W resulted in attenuated astrocytic glucose uptake via GLUT1, leading to reduced lactate production and a switch from homeostatic to reactive astrocytes. Importantly, lactate supplementation or a ketogenic diet restored neuronal oxidative phosphorylation and reversed cognitive deficits in SNX27R196W mice. In summary, we illustrate a key role for astrocytic SNX27 in maintaining glucose supply and glycolysis and reveal that altered astrocytic metabolism disrupts the astrocyte-neuron interaction, which contributes to ID. Our work also suggests a feasible strategy for treating ID by restoring astrocytic metabolic function.

Impact of metacognition on attitudes toward epilepsy in medical students.

PURPOSE: This study evaluated medical students' knowledge and attitudes toward epilepsy and the influence of metacognition thereon. METHOD: Valid questionnaires were administered to medical students including undergraduate, professional postgraduate, and standardized residency training students (N = 503). The questionnaire had 4 parts: demographic information, knowledge of epilepsy, attitudes toward epilepsy, and metacognitive assessment. The Chinese Public Attitudes Toward Epilepsy scale and 30-Item Metacognition Questionnaire were used to assess attitudes and metacognition, respectively. RESULTS: Almost all participants had heard of epilepsy; 38.8% had witnessed a seizure and 25% were acquainted with a person with epilepsy. The proportion of correct answers to epilepsy-related knowledge ranged from 40.6% (Putting an object into the mouth of a person experiencing an epileptic seizure) to 97% (Convulsion is a symptom of epilepsy). However, knowledge of epilepsy was not able to affect attitudes toward epilepsy. Age, years of clinical experience, having witnessed a seizure, positive belief of worry, and need to control thinking were correlated with the different domains of attitude toward epilepsy. When participants were divided into 2 groups-i.e., those with high and low knowledge of epilepsy, participants in the former group who had a positive belief of worry or had not witnessed any seizures were more likely to have negative attitudes toward epilepsy. CONCLUSION: Medical students showed good awareness of the etiology and symptoms of epilepsy. Overall, attitudes toward epilepsy were negative. A positive belief of worry was associated with a more negative attitude toward epilepsy among respondents with greater knowledge of epilepsy.

A first-principles study on the multiferroicity of semi-modified X2M (X = C, Si; M = F, Cl) monolayers.

The research of two-dimensional multiferroic materials has attracted extensive attention in recent years. In this work, we systematically investigated the multiferroic properties of semi-fluorinated and semi-chlorinated graphene and silylene X2M (X = C, Si; M = F, Cl) monolayers under strain using first principles calculations based on density functional theory. We find that the X2M monolayer has a frustrated antiferromagnetic order, and a large polarization with a high reversal potential barrier. When increasing the applied biaxial tensile strain, the magnetic order remains unchanged, but the polarization flipping potential barrier of X2M gradually decreases. When the strain increases to 35%, although the energy required to flip the fluorine and chlorine atoms is still very high in the C2F and C2Cl monolayers, it goes down to 312.5 meV and 260 meV in unit cells of the Si2F and Si2Cl monolayers, respectively. At the same time, both semi-modified silylenes exhibit metallic ferroelectricity with a band gap of at least 0.275 eV in the direction perpendicular to the plane. The results of these studies show that Si2F and Si2Cl monolayers may become a new generation of information storage materials with magnetoelectric multifunctional properties.

α-Terpineol affects social immunity, increasing the pathogenicity of entomopathogenic nematodes to subterranean termites (Isoptera).

Biocontrol of subterranean termites is largely impeded by their social immune responses. Studies on biocontrol agents combined with natural insecticides and their possible effects on the immune defense mechanisms of termites are limited. In this study, we investigated the effects of a combined biocontrol strategy using a plant-derived insect ATPase inhibitor, α-terpineol, with the entomopathogenic nematodes (EPNs) Steinernema carpocapsae against the subterranean termite Coptotermes formosanus Shiraki. Survival assays showed that even a low lethal concentration of α-terpineol significantly increased the EPNs-induced virulence in C. formosanus. α-terpineol treatment majorly inhibited the activity of Na+- K+- ATPase, which disturbed the EPNs-induced enhancement of locomotor activity and grooming behavior in termites treated with the combined strategy. Furthermore, the combination treatment had a synergistic inhibitory effect on innate immune responses in C. formosanus, which were measured as changes in the expression of immune-related genes and activities of immune system enzymes. In conclusion, α-terpineol can weaken the immune defense of termites against EPNs at low lethal concentrations, and is a suitable non-synthetic insecticide to prove the biocontrol efficiency of EPNs on C. formosanus. This study provides a theoretical basis and technical reference for a novel biocontrol strategy that promises to overcome the problems of host immune defense in termites.

Noise effective masking level for bone conduction of wide-spectrum short-duration signals in normal hearing adults.

OBJECTIVE: The objective of this study is to determine the noise effective masking level (EML) and inter-aural attenuation (IA) for click and CE-Chirp signals presented though a Radioear B-81 to elicit the auditory brainstem responses in normally hearing, young adults. DESIGN AND STUDY SAMPLE: A total of 26 conveniently sampled adults (13 male and 13 female, aged 18-25 years; 52 ears), with pure-tone hearing thresholds not >15 dB nHL at octave frequencies from 250 to 8000 Hz, and subjective thresholds for the bone-conducted click and CE-Chirp not >10 dB nHL. RESULTS: At stimulus intensities of 30 and 40 dB nHL, the contralateral EML was 67.86 ± 0.78 and 77.80 ± 0.81 dB SPL (respectively) for the click and 72.11 ± 0.74 and 83.53 ± 0.78 dB SPL (respectively) for the CE-Chirp. At stimulus intensities of 30 and 40 dB nHL, the IA was 3.46 ± 2.34 and 3.38 ± 2.03 dB (respectively) for both the click and the CE-Chirp. CONCLUSION: EML and IA values are reported for click and CE-Chirp signals presented at 30 and 40 dB nHL though a Radioear B-81 to elicit the ABR in normally hearing, young adults.

Shear wave elastography parameters adds prognostic value to adverse outcome in kidney transplantation recipients.

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma.

BACKGROUND: Liver carcinoma generally presents as an immunosuppressive microenvironment that promotes tumor evasion. The intercellular crosstalk of immune cells significantly influences the construction of an immunosuppressive microenvironment. This study aimed to investigate the important interactions between immune cells and their targeting drugs in liver carcinoma, by using single-cell and bulk transcriptomic data. METHODS: Single-cell and bulk transcriptomic data were retrieved from Gene Expression Omnibus (GSE159977, GSE136103, and GSE125449) and The Cancer Genome Atlas (TGCA-LIHC), respectively. Quality control, dimension reduction, clustering, and annotation were performed according to the Scanpy workflow based on Python. Cell-cell interactions were explored using the CellPhone database and CellChat. Trajectory analysis was executed using a partition-based graph abstraction method. The transcriptomic factors (TFs) were predicted using single-cell regulatory network inference and clustering (SCENIC). The target genes from TFs were used to establish a related score based on the TCGA cohort; this score was subsequently validated by survival, gene set enrichment, and immune cell infiltration analyses. Drug prediction was performed based on the Cancer Therapeutics Response Portal and PRISM Repurposing datasets. RESULTS: Thirty-one patients at four different states, including health, hepatitis, cirrhosis, and cancer, were enrolled in this study. After dimension reduction and clustering, twenty-two clusters were identified. Cell-cell interaction analyses indicated that macrophage-naive CD4 + T cell interaction significantly affect cancerous state. In brief, macrophages interact with naive CD4 + T cells via different pathways in different states. The results of SCENIC indicated that macrophages present in cancer cells were similar to those present during cirrhosis. A macrophage-naive CD4 + T cell (MNT) score was generated by the SCENIC-derived target genes. Based on the MNT score, five relevant drugs (inhibitor of polo-like kinase 1, inhibitor of kinesin family member 11, dabrafenib, ispinesib, and epothilone-b) were predicted. CONCLUSIONS: This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies.

Catechol-containing compounds are a broad class of protein aggregation inhibitors: Redox state is a key determinant of the inhibitory activities.

A range of neurodegenerative and related aging diseases, such as Alzheimer's disease and type 2 diabetes, are linked to toxic protein aggregation. Yet the mechanisms of protein aggregation inhibition by small molecule inhibitors remain poorly understood, in part because most protein targets of aggregation assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization of protein-inhibitor complexes and structural-based inhibitor design. Herein we employed a parallel small molecule library-screening approach to identify inhibitors against three prototype amyloidogenic proteins in neurodegeneration and related proteinopathies: amylin, Aß and tau. One remarkable class of inhibitors identified from these screens against different amyloidogenic proteins was catechol-containing compounds and redox-related quinones/anthraquinones. Secondary assays validated most of the identified inhibitors. In vivo efficacy evaluation of a selected catechol-containing compound, rosmarinic acid, demonstrated its strong mitigating effects of amylin amyloid deposition and related diabetic pathology in transgenic HIP rats. Further systematic investigation of selected class of inhibitors under aerobic and anaerobic conditions revealed that the redox state of the broad class of catechol-containing compounds is a key determinant of the amyloid inhibitor activities. The molecular insights we gained not only explain why a large number of catechol-containing polyphenolic natural compounds, often enriched in healthy diet, have anti-neurodegeneration and anti-aging activities, but also could guide the rational design of therapeutic or nutraceutical strategies to target a broad range of neurodegenerative and related aging diseases.

Several non-salt and solid thienopyridine derivatives as oral P2Y12 receptor inhibitors with good stability.

A series of novel thienopyridine derivatives were designed and synthesized as P2Y12 receptor inhibitors. Several solid compounds were assessed for inhibitory effect where they exhibited stronger potency than clopidogrel. Compound 6b and 6g were evaluated for metabolism to verify that they could overcome clopidogrel resistance and for toxicity where they showed lower toxicity than prasugrel. Compound 6b exhibited lower risk of bleeding than prasugrel and showed good stability under stress testing. Overall, as a promising antiplatelet agent, representative compound 6b showed the following advantages: (1) no drug resistance for CYP2C19 poor metabolizers; (2) higher potency than clopidogrel; (3) lower toxicity than prasugrel; (4) lower risk of bleeding than prasugrel; (5) good stability as a non-salt solid.

Prediction of two-dimensional monolayer C2O2Fe with chiral magnetic and ferroelectric orders.

Low-dimensional multiferroics are highly desired for applications and contain exotic physical properties. Here we predict a two-dimensional material, C2O2Fe monolayer, through Fe intercalation in the graphene oxide monolayer. The crystal stable texture, chiral spin order, and ferroelectric polarization of the C2O2Fe monolayer are theoretically studied by considering the electron on-site Coulomb interaction and spin orbit coupling, which also manifests the ferroelectric polarization and reversal barrier at 30% biaxial tensile strain comparable with the other two-dimensional ferroelectric materials, such as GeS and GeSe. Moreover, first-principles calculations show that the polarization flipping is accompanied by spin orientation reversal, when the ferroelectric polarization is upward to the plane, a clockwise chiral antiferromagnetic ground state is obtained, while when the polarization is downward, the monolayer shows the anticlockwise chiral antiferromagnetic structure. In this sense, a strong electrically controlled magnetism exists in the designed C2O2Fe monolayer film.

The effect of amending soils with biochar on the microhabitat preferences of Coptotermes formosanus (Blattodea: Rhinotermitidae).

Biochar has attracted worldwide attention owing to its potential for mitigating greenhouse gas emissions, improving soil properties, increasing plant growth and so on. While, the assessment of a substantial amount of security is required to determine before biochar is more extensively applied. Our goal was to evaluate the security of biochar by determining the effect of biochar on the preference of soil arthropods for microhabitats. In this study, we examined the effect of varying amounts of biochar on the preference of the Formosan subterranean termite (Coptotermes formosanus) to microhabitats. In addition, we analyzed key soil characteristics to explore their relevance to the termite preferences. Our results found that when compared with 0% (control soil), there was no preference when 2.5% and 5% of biochar were applied. The application of >5% biochar repelled the termites, which then left these soils. Their fresh weight and rates of survival also decreased. The soil pH increased, but the humidity decreased when >5% of biochar was applied. Soil bacteria composition when biochar was amended at 20% also differed from 0% and 2.5% applications. The relative abundance of Cellvibrio and Flavisolibacter in 20% were significantly higher than 0% and 2.5%, while the relative abundance of Burkholderia, Candidatus_Solibacter, Dyella, Edaphobacter, Fulvimonas and Occallatibacter were significantly lower than them. And the functional results predicted by Bugbase suggested that biochar application can cause an increase in the soil potentially pathogen phenotype. In conclusion, our research indicated that biochar can affect the preference of termites for microhabitats and changes in the characteristics of soil might cause changes in these preferences. In addition, our results suggest that soil that has been amended with >10% biochar has the potential to control termites.

Is it important to measure the internal spermatic vein diameter after varicocelectomy? A self-controlled trial.

To analyse spermatic vein parameters and post-varicocelectomy diagnostic ultrasound methods by comparing pre- and post-operative ultrasound parameters and semen quality in patients undergoing varicocelectomy. Ultrasound and semen analyses were performed within 1 week before surgery and 3 months after surgery in 125 patients who underwent varicocelectomy for infertility. Patients were divided into three groups according to the post-operative internal diameter of the spermatic vein and reflux: recovery, dilatation, and reflux. Changes in semen quality before and after surgery were compared between groups. Sperm concentration, motility, and morphology were significantly improved (p < 0.05); however, semen volume did not improve (p > 0.05) in patients in the recovery and dilatation groups compared to those in patients before surgery. Sperm concentration, motility, and semen volume did not improve in patients in the reflux group compared with those in patients before surgery (p > 0.05). Logistic regression analysis revealed that the internal diameter of the spermatic vein and reflux duration were risk factors for post-operative spermatic vein dilatation without reflux. Ultrasonography after varicocelectomy should primarily be used to observe reflux, and should not be used as a diagnostic criterion for varicocele based on the internal diameter of the spermatic vein alone.

Comparative assessment of manual chart review and ICD claims data in evaluating immunotherapy-related adverse events.

BACKGROUND: The aim of this retrospective study was to demonstrate that irAEs, specifically gastrointestinal and pulmonary, examined through International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs, thereby concluding that ICD claims data are a poor approach to electronic health record (EHR) data mining for irAEs in immunotherapy clinical research. METHODS: This retrospective analysis was conducted in 1,063 cancer patients who received ICIs between 2011 and 2017. We identified irAEs by manual review of medical records to determine the incidence of each of our endpoints, namely colitis, hepatitis, pneumonitis, other irAE, or no irAE. We then performed a secondary analysis utilizing ICD claims data alone using a broad range of symptom and disease-specific ICD codes representative of irAEs. RESULTS: 16% (n = 174/1,063) of the total study population was initially found to have either pneumonitis 3% (n = 37), colitis 7% (n = 81) or hepatitis 5% (n = 56) on manual review. Of these patients, 46% (n = 80/174) did not have ICD code evidence in the EHR reflecting their irAE. Of the total patients not found to have any irAEs during manual review, 61% (n = 459/748) of patients had ICD codes suggestive of possible irAE, yet were not identified as having an irAE during manual review. DISCUSSION: Examining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs.

Deep Network With Approximation Error Being Reciprocal of Width to Power of Square Root of Depth.

A new network with super-approximation power is introduced. This network is built with Floor (⌊x⌋) or ReLU (max{0,x}) activation function in each neuron; hence, we call such networks Floor-ReLU networks. For any hyperparameters N∈N+ and L∈N+, we show that Floor-ReLU networks with width max{d,5N+13} and depth 64dL+3 can uniformly approximate a Hölder function f on [0,1]d with an approximation error 3λdα/2N-αL, where α∈(0,1] and λ are the Hölder order and constant, respectively. More generally for an arbitrary continuous function f on [0,1]d with a modulus of continuity ωf(·), the constructive approximation rate is ωf(dN-L)+2ωf(d)N-L. As a consequence, this new class of networks overcomes the curse of dimensionality in approximation power when the variation of ωf(r) as r→0 is moderate (e.g., ωf(r)≲rα for Hölder continuous functions), since the major term to be considered in our approximation rate is essentially d times a function of N and L independent of d within the modulus of continuity.

Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer's disease.

In our continuing efforts to develop novel neuroprotectants for Alzheimer's disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH3 on the indole ring of the lead compound. The results also demonstrated that the ß-keto moiety can be modified to retain or improve the neuroprotective activity. Docking studies of selected analogs to the FMN site of mitochondrial complex I also supported the observed neuroprotective activities. Collectively, the results provide further information to guide optimization and development of analogs based on this chemical scaffold as neuroprotectants with a novel mechanism of action for AD.

Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome.

We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [11C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain. [11C]1, thus suggesting the potential to serve as a useful tool for imaging NLRP3 inflammasome in living brains.