A retrospective study to determine the correlation among HBV PreS1 antigen, HBV e antigen, alanine aminotransferase, and HBV DNA.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection presents with indicators of varying clinical significance. We aimed to evaluate the correlation among HBV Pre-S1 antigen (HBV PreS1-Ag), HBV e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed 6180 serum samples collected between 2020 and 2022 at the Shanghai General Hospital, China. Data regarding PreS1-Ag, HBeAg, ALT, and HBV DNA were compiled. Correlation analyses and cross-tabulations were employed to explore the diagnostic indicators. RESULTS: The detection rates of both antigen indicators showed a proportional increase with HBV DNA loads. The correlation between PreS1-Ag and HBV DNA (r = 0.616) was stronger than that between HBeAg and HBV DNA (r = 0.391). The specificity of PreS1-Ag (84.30 %) was lower than that of HBeAg (97.44 %), whereas the sensitivity of HBeAg (91.13 %) significantly surpassed that of PreS1-Ag (29.56 %). Among the HBV DNA positive patients, 92.04 % tested positive for at least one indicator, which exceeded the rate of PreS1+HBeAg- and PreS1-HBeAg+ (52. 28 % and 68. 56 %, respectively). Only 1.75 % of the patients exhibited double negativity, which was lower than the percentage of patients with single negativity (1.95 % and 12.00 % for PreS1-Ag and HBeAg, respectively). The PreS1 levels correlated with ALT levels (r = 0.317); patients with PreS1-positive status had higher ALT levels than patients with PreS1-negative status. CONCLUSION: PreS1-Ag is a more robust HBV replication indicator than HBeAg. PreS1-Ag displayed high sensitivity, whereas HBeAg demonstrated high specificity. Moreover, PreS1-Ag levels correlated with ALT levels. A combination of these indicators demonstrated dependable clinical value for detecting HBV infection and evaluating liver function.

CO2-Based Stable Porous Metal-Organic Frameworks for CO2 Utilization.

The transformation of carbon dioxide (CO2) into functional materials has garnered considerable worldwide interest. Metal-organic frameworks (MOFs), as a distinctive class of materials, have made great contributions to CO2 capture and conversion. However, facile conversion of CO2 to stable porous MOFs for CO2 utilization remains unexplored. Herein, we present a facile methodology of using CO2 to synthesize stable zirconium-based MOFs. Two zirconium-based MOFs CO2-Zr-DEP and CO2-Zr-DEDP with face-centered cubic topology were obtained via a sequential desilylation-carboxylation-coordination reaction. The MOFs exhibit excellent crystallinity, as verified through powder X-ray diffraction and high-resolution transmission electron microscopy analyses. They also have notable porosity with high surface area (SBET up to 3688 m2 g-1) and good CO2 adsorption capacity (up to 12.5 wt %). The resulting MOFs have abundant alkyne functional moieties, confirmed through 13C cross-polarization/magic angle spinning nuclear magnetic resonance and Fourier transform infrared spectra. Leveraging the catalytic prowess of Ag(I) in diverse CO2-involved reactions, we incorporated Ag(I) into zirconium-based MOFs, capitalizing on their interactions with carbon-carbon π-bonds of alkynes, thereby forming a heterogeneous catalyst. This catalyst demonstrates outstanding efficiency in catalyzing the conversion of CO2 and propargylic alcohols into cyclic carbonates, achieving >99% yield at room temperature and atmospheric pressure conditions. Thus, this work provides a dual CO2 utilization strategy, encompassing the synthesis of CO2-based MOFs (20-24 wt % from CO2) and their subsequent application in CO2 capture and conversion processes. This approach significantly enhances overall CO2 utilization.

Predictive models for lymph node metastasis in endometrial cancer: A systematic review and bibliometric analysis.

BACKGROUND: Lymph node metastasis is associated with a poorer prognosis in endometrial cancer. OBJECTIVE: The objective was to synthesize and critically appraise existing predictive models for lymph node metastasis risk stratification in endometrial cancer. DESIGN: This study is a systematic review. DATA SOURCES AND METHODS: We searched the Web of Science for articles reporting models predicting lymph node metastasis in endometrial cancer, with a systematic review and bibliometric analysis conducted based upon which. Risk of bias was assessed by the Prediction model Risk Of BiAS assessment Tool (PROBAST). RESULTS: A total of 64 articles were included in the systematic review, published between 2010 and 2023. The most common articles were "development only." Traditional clinicopathological parameters remained the mainstream in models, for example, serum tumor marker, myometrial invasion and tumor grade. Also, models based upon gene-signatures, radiomics and digital histopathological images exhibited an acceptable self-reported performance. The most frequently validated models were the Mayo criteria, which reached a negative predictive value of 97.1%-98.2%. Substantial variability and inconsistency were observed through PROBAST, indicating significant between-study heterogeneity. A further bibliometric analysis revealed a relatively weak link between authors and organizations on models predicting lymph node metastasis in endometrial cancer. CONCLUSION: A number of predictive models for lymph node metastasis in endometrial cancer have been developed. Although some exhibited promising performance as they demonstrated adequate to good discrimination, few models can currently be recommended for clinical practice due to lack of independent validation, high risk of bias and low consistency in measured predictors. Collaborations between authors, organizations and countries were weak. Model updating, external validation and collaborative research are urgently needed. REGISTRATION: None.

Introduction to predictive models for lymph node metastasis in endometrial cancerLymph node metastasis of endometrial cancer is associated with a poor prognosis. There are currently many predictive models. We summarized and evaluated them in this article.

Design, synthesis and biological evaluation of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety as iron chelators.

The avidity of cancer cells for iron highlights the potential for iron chelators to be used in cancer therapy. Herein, we designed and synthesized a novel series of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety using a ring-fusion strategy based on the structure of an iron chelator, VLX600. The antiproliferative activity evaluation against cancer cells and normal cells led to the identification of compound 3k, which displayed the strongest antiproliferative activity in vitro against A549, MCF-7, Hela and HepG-2 with IC50 values of 0.59, 0.86, 1.31 and 0.92 µM, respectively, and had lower cytotoxicity against HEK293 than VLX600. Further investigations revealed that unlike VLX600, compound 3k selectively bound to ferrous ions, but not to ferric ions, and addition of Fe2+ abolished the cytotoxicity of 3k. Flow cytometry assays demonstrated that 3k arrested the cell cycle at the G1 phase and induced significant apoptosis in A549 cells in dose and time-dependent manners, corresponding to JC-1 staining assay results. Western blot analysis of Bcl-2, Bax and cleaved caspase-3 proteins further provided evidences that induction of apoptosis by 3k in A549 cells might be at least via the mitochondria pathway. These above results highlight that 3k is a valuable lead compound that deserves further investigation as an iron chelator for the treatment of cancer.

Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations.

Calcium homeostasis imbalance in the body can lead to a variety of chronic diseases. Supplement efficiency is essential. Peptide calcium chelate, a fourth-generation calcium supplement, offers easy absorption and minimal side effects. Its effectiveness relies on peptide's calcium binding capacity. However, research on amino acid sequences in peptides with high calcium binding capacity (HCBC) is limited, affecting the efficient identification of such peptides. This study used soybean peptides (SP), separated and purified by gel chromatography, to obtain HCBC peptide (137.45 µg mg-1) and normal peptide (≤95.78 µg mg-1). Mass spectrometry identified the sequences of these peptides, and an analysis of the positional distribution of characteristic amino acids followed. Two HCBC peptides with sequences GGDLVS (271.55 µg mg-1) and YEGVIL (272.54 µg mg-1) were discovered. Molecular dynamics showed that when either aspartic acid is located near the N-terminal's middle, or glutamic acid is near the end, or in cases of continuous Asp or Glu, the binding speed, probability, and strength between the peptide and calcium ions are superior compared to those at other locations. The study's goal was to clarify how the positions of characteristic amino acids in peptides affect calcium binding, aiding in developing peptide calcium chelates as a novel calcium supplement.

Immediate versus delayed single blastocyst transfer following the first stimulated IVF cycle in the freeze-all strategy: a study protocol for a randomised controlled trial.

INTRODUCTION: In recent years, the use of frozen embryo transfers (FET) has rapidly increased following the freeze-all strategy due to the advantages of increased maternal safety, improved pregnancy rates, lower ectopic pregnancy rates and better obstetric and neonatal outcomes. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated in vitro fertilisation (IVF) cycle in the freeze-all strategy. METHODS/ANALYSIS: This will be a randomised controlled trial. A total of 828 women undergoing their first FET following their first stimulated IVF cycle in the freeze-all strategy will be enrolled and randomised into one of the following groups according to a computer-generated randomisation list: (1) the immediate group, in which FET will be performed in the first menstrual cycle following the stimulated IVF cycle; or (2) the delayed group, in which FET will be performed at least in the second menstrual cycle following the stimulated IVF cycle. The primary outcome will be live birth, which is defined as the delivery of any infants at ≥22 gestational weeks with heartbeat and breath. ETHICS/DISSEMINATION: Ethical approval was granted by the Ethics Committee of Assisted Reproductive Medicine at the Shanghai JiAi Genetics & IVF Institute (JIAI E2019-15). Written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04371783.

Hydroxyl-Bonded Co Single Atom Site on Boroncarbonitride Surface Realizes Non-sacrificial H2O2 Synthesis in the Near-Infrared Region.

Photocatalytic synthesis of hydrogen peroxide (H2O2) from O2 and H2O under near-infrared light is a sustainable renewable energy production strategy, but challenging reaction. The bottleneck of this reaction lies in the regulation of O2 reduction path by photocatalyst. Herein, we construct the center of the one-step two-electron reduction (OSR) pathway of O2 for H2O2 evolution via the formation of the hydroxyl-bonded Co single-atom sites on boroncarbonitride surface (BCN-OH2/Co1). Our experimental and theoretical prediction results confirm that the hydroxyl group on the surface and the electronic band structure of BCN-OH2/Co1 are the key factor in regulating the O2 reduction pathway. In addition, the hydroxyl-bonded Co single-atom sites can further enrich O2 molecules with more electrons, which can avoid the one-electron reduction of O2 to •O2 -, thus promoting the direct two-electron activation hydrogenation of O2. Consequently, BCN-OH2/Co1 exhibited a high H2O2 evolution apparent quantum efficiency of 0.8% at 850 nm, better than most of the previously reported photocatalysts. This study reveals an important reaction pathway for the generation of H2O2, emphasizing that precise control of the active site structure of the photocatalyst is essential for achieving efficient conversion of solar-to-chemical. This article is protected by copyright. All rights reserved.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Assessing spatiotemporal risks of nonpoint source pollution via soil erosion: a coastal case in the Yellow River Delta, China.

Nonpoint source pollution (NPSP) has always been the dominant threat to regional waters. Based on empirical models of the revised universal soil loss equation and the phosphorus index, an NPSP risk assessment model denoted as SL-NPSRI was developed. The surface soil pollutant loss was estimated by simulating the rain-runoff topographic process, and the influence of path attenuation was quantified. A case study in the Yellow River Delta and corresponding field surveys of soil pollutants and water quality showed that the established model can be applied to evaluate the spatial heterogeneity of NPSP. NPSP usually occurs during high-intensity rainfall periods and in larger estuaries. Summer rainfall increased pollutant transport into the sea from late July to mid-August and caused estuarine dilution. Higher NPSP risks often correspond to coastal areas with lower vegetation coverage, higher soil erodibility, and higher soil pollutant concentrations. Agricultural NPSP originating from cropland significantly increase the pollutant fluxes. Therefore, area-specific land use management and vegetation coverage improvement, and temporal-specific strategies can be explored for NPSP control during source-transport hydrological processes. This research provides a novel insight for coastal NPSP simulations by comprehensively analyzing the soil erosion process and its associated pollutant loss effects, which can be useful for targeted spatiotemporal solutions.

The Diagnostic Value of the Modified STdmax/MET Criterion in Treadmill Exercise Electrocardiographic Test for Coronary Artery Disease in an Aged Population.

Objective: The primary objective of this study is to assess the diagnostic value of treadmill exercise electrocardiographic test (EET) for coronary artery disease (CAD) in the aged population, emphasizing the need for improved diagnostic criteria due to the limitations of traditional EET in accurately diagnosing CAD among elderly patients. This focus is critical as the aged population has a higher prevalence of CAD, and early and accurate diagnosis is essential for effective management and treatment. Methods: This study comprised two stages. Initially, we retrospectively analyzed data from patients aged > 60 years who underwent treadmill EET within two weeks of coronary angiography (CAG) during hospitalization from June 1, 2014, to May 31, 2017. We evaluated the diagnostic value of treadmill EET using both the standard criterion (ST depression > 0.1 mV) and a modified criterion (the ratio of ST depression to metabolic equivalent [STdmax/MET]), explaining our choice of the modified criterion as it potentially offers a more nuanced assessment by considering the patient's exercise capacity. A subgroup analysis was also conducted. Subsequently, a prospective study to further investigate the modified criterion was carried out. Results: In the retrospective analysis, 190 patients were enrolled, with 71.5% confirmed to have CAD. The sensitivity, specificity, and accuracy of the standard criterion were 66.2%, 42.6%, and 59.5%, respectively. With a cut-off value for STdmax/MET set at 0.255 mV·W/m2, these metrics improved to 79.4%, 55.7%, and 72.4%, respectively, for the modified criterion. The prospective study, involving 47 patients, confirmed significant improvements in sensitivity (85.7% vs. 64.3%, P = .041) and specificity (68.4% vs. 31.6%, P = .046) when applying the modified criterion. Conclusions: The introduction of the novel modified diagnostic criterion, STdmax/MET, significantly enhances the diagnostic value of treadmill EET for detecting CAD in elderly patients. The adoption of this modified criterion could potentially improve clinical outcomes by facilitating more accurate and timely diagnosis of CAD in this high-risk group.

A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Nature-Inspired Micro/Nano-Structured Antibacterial Surfaces.

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.

Efficacy and safety of robotic versus laparoscopic liver resection for hepatocellular carcinoma: a propensity score-matched retrospective cohort study.

BACKGROUND: Evidence concerning long-term outcome of robotic liver resection (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients is scarce. METHODS: This study enrolled all patients who underwent RLR and LLR for resectable HCC between July 2016 and July 2021. Propensity score matching (PSM) was employed to create a 1:3 match between the RLR and LLR groups. A comprehensive collection and analysis of patient data regarding efficacy and safety have been conducted, along with the evaluation of the learning curve for RLR. RESULTS: Following PSM, a total of 341 patients were included, with 97 in the RLR group and 244 in the LLR group. RLR group demonstrated a significantly longer operative time (median [IQR], 210 [152.0-298.0] min vs. 183.5 [132.3-263.5] min; p = 0.04), with no significant differences in other perioperative and short-term postoperative outcomes. Overall survival (OS) was similar between the two groups (p = 0.43), but RLR group exhibited improved recurrence-free survival (RFS) (median of 65 months vs. 56 months, p = 0.006). The estimated 5-year OS for RLR and LLR were 74.8% (95% CI: 65.4-85.6%) and 80.7% (95% CI: 74.0-88.1%), respectively. The estimated 5-year RFS for RLR and LLR were 58.6% (95% CI: 48.6-70.6%) and 38.3% (95% CI: 26.4-55.9%), respectively. In the multivariate Cox regression analysis, RLR (HR: 0.586, 95% CI (0.393-0.874), p = 0.008) emerged as an independent predictor of reducing recurrence rates and enhanced RFS. The operative learning curve indicates that approximately after the 11th case, the learning curve of RLR stabilized and entered a proficient phase. CONCLUSIONS: OS was comparable between RLR and LLR, and while RFS was improved in the RLR group. RLR demonstrates oncological effectiveness and safety for resectable HCC.

Synthesis of ZSM-5 Zeolite Nanosheets with Tunable Silanol Nest Contents across an Ultra-wide pH Range and Their Catalytic Validation.

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.

Conjugation of Soybean Proteins 7S/11S Isolate with Glucose/Fructose in Gels through Wet-Heating Maillard Reaction.

Conjugation with glucose (G) and fructose (F) via the Maillard reaction under the wet-heating condition is a natural and non-toxic method of improving the technological functions of 7S/11S proteins in different kinds of gels. It may be used as an affordable supply of emulsifiers and an excellent encapsulating matrix for gels. This study aimed to create a glucose/fructose-conjugated 7S/11S soy protein via the Maillard reaction. The conjugation was confirmed by determining the SDS-PAGE profile and circular dichroism spectra. In addition, these conjugates were comprehensively characterized in terms of grafting degree, browning degree, sulfhydryl content, surface hydrophobicity (H0), and differential scanning calorimetry (DSC) through various reaction times (0, 24, 48, and 72 h) to evaluate their ability to be used in food gels. The functional characteristics of the 7S/11S isolate-G/F conjugate formed at 70 °C, with a high degree of glycosylation and browning, were superior to those obtained at other reaction times. The SDS-PAGE profile indicated that the conjugation between the 7S and 11S proteins and carbohydrate sources of G and F through the Maillard reaction occurred. Secondary structural results revealed that covalent interactions with G and F affected the secondary structural components of 7S/11S proteins, leading to increased random coils. When exposed to moist heating conditions, G and F have significant potential for protein alteration through the Maillard reaction. The results of this study may provide new insights into protein modification and establish the theoretical basis for the therapeutic application of both G and F conjugation with soy proteins in different food matrixes and gels.

Weighted Gene Co-expression Network Analysis and Machine Learning Validation for Identifying Major Genes Related to Sjogren's Syndrome.

Sjogren's syndrome (SS) is an autoimmune disorder characterized by dry mouth and dry eyes. Its pathogenic mechanism is currently unclear. This study aims to integrate weighted gene co-expression network analysis (WGCNA) and machine learning to identify key genes associated with SS. We downloaded 3 publicly available datasets from the GEO database comprising the gene expression data of 231 SS and 78 control cases, including GSE84844, GSE48378 and GSE51092, and carried out WGCNA to elucidate differences in the abundant genes. Candidate biomarkers for SS were then identified using a LASSO regression model. Totally 6 machine-learning models were subsequently utilized for validating the biological significance of major genes according to their expression. Finally, immune cell infiltration of the SS tissue was assessed using the CIBERSORT algorithm. A weighted gene co-expression network was built to divide genes into 10 modules. Among them, blue and red modules were most closely associated with SS, and showed significant enrichment in type I interferon signaling, cellular response to type I interferon and response to virus, etc. Combined machine learning identified 5 hub genes, including OAS1, EIF2AK2, IFITM3, TOP2A and STAT1. Immune cell infiltration analysis showed that SS was associated with CD8+ T cell, CD4+ T cell, gamma delta T cell, NK cell and dendritic cell activation. WGCNA was combined with machine learning to uncover genes that may be involved in SS pathogenesis, which can be utilized for developing SS biomarkers and appropriate therapeutic targets.

Efficient ammonia synthesis from the air using tandem non-thermal plasma and electrocatalysis at ambient conditions.

While electrochemical N2 reduction presents a sustainable approach to NH3 synthesis, addressing the emission- and energy-intensive limitations of the Haber-Bosch process, it grapples with challenges in N2 activation and competing with pronounced hydrogen evolution reaction. Here we present a tandem air-NOx-NOx--NH3 system that combines non-thermal plasma-enabled N2 oxidation with Ni(OH)x/Cu-catalyzed electrochemical NOx- reduction. It delivers a high NH3 yield rate of 3 mmol h-1 cm-2 and a corresponding Faradaic efficiency of 92% at -0.25 V versus reversible hydrogen electrode in batch experiments, outperforming previously reported ones. Furthermore, in a flow mode concurrently operating the non-thermal plasma and the NOx- electrolyzer, a stable NH3 yield rate of approximately 1.25 mmol h-1 cm-2 is sustained over 100 h using pure air as the intake. Mechanistic studies indicate that amorphous Ni(OH)x on Cu interacts with hydrated K+ in the double layer through noncovalent interactions and accelerates the activation of water, enriching adsorbed hydrogen species that can readily react with N-containing intermediates. In situ spectroscopies and density functional theory (DFT) results reveal that NOx- adsorption and their hydrogenation process are optimized over the Ni(OH)x/Cu surface. This work provides new insights into electricity-driven distributed NH3 production using natural air at ambient conditions.

L-AP Alleviates Liver Injury in Septic Mice by Inhibiting Macrophage Activation via Suppressing NF-κB and NLRP3 Inflammasome/Caspase-1 Signal Pathways.

Liver injury and progressive liver failure are severe life-threatening complications in sepsis, further worsening the disease and leading to death. Macrophages and their mediated inflammatory cytokine storm are critical regulators in the occurrence and progression of liver injury in sepsis, for which effective treatments are still lacking. l-Ascorbic acid 6-palmitate (L-AP), a food additive, can inhibit neuroinflammation by modulating the phenotype of the microglia, but its pharmacological action in septic liver damage has not been fully explored. We aimed to investigate L-AP's antisepticemia action and the possible pharmacological mechanisms in attenuating septic liver damage by modulating macrophage function. We observed that L-AP treatment significantly increased survival in cecal ligation and puncture-induced WT mice and attenuated hepatic inflammatory injury, including the histopathology of the liver tissues, hepatocyte apoptosis, and the liver enzyme levels in plasma, which were comparable to NLRP3-deficiency in septic mice. L-AP supplementation significantly attenuated the excessive inflammatory response in hepatic tissues of septic mice in vivo and in cultured macrophages challenged by both LPS and ATP in vitro, by reducing the levels of NLRP3, pro-IL-1ß, and pro-IL-18 mRNA expression, as well as the levels of proteins for p-I-κB-α, p-NF-κB-p65, NLRP3, cleaved-caspase-1, IL-1ß, and IL-18. Additionally, it impaired the inflammasome ASC spot activation and reduced the inflammatory factor contents, including IL-1ß and IL-18 in plasma/cultured superannuants. It also prevented the infiltration/migration of macrophages and their M1-like inflammatory polarization while improving their M2-like polarization. Overall, our findings revealed that L-AP protected against sepsis by reducing macrophage activation and inflammatory cytokine production by suppressing their activation in NF-κB and NLRP3 inflammasome signal pathways in septic liver.

Design, Synthesis, and Evaluation of 8-(o-Tolyl)quinazoline Derivatives as Small-Molecule PD-1/PD-L1 Antagonists.

Small-molecule inhibitors targeting programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions can compensate for the shortcomings of antibody-based inhibitors and have attracted considerable attention, some of which have already entered clinical trials. Herein, based on our previous study on small-molecule PD-L1 inhibitors, we reported a series of 8-(o-tolyl)quinazoline derivatives by the skeleton merging strategy. Homogenous time-resolved fluorescence (HTRF) assay against PD-1/PD-L1 interaction identified compound A5, which showed the most potent inhibition with an IC50 value of 23.78 nM. Meanwhile, based on the results of HTRF assay, the structure-activity relationships (SARs) of the tail were focused on. Cell-based PD-1/PD-L1 blockade assay further revealed that A5 significantly blocked the PD-1/PD-L1 interaction at 1.1 µM in the co-culture system of Jurkat-NFAT-PD-1 cells and Hep3B-OS8-hPD-L1 cells with no significant cytotoxicity on Jurkat cells. Moreover, the proposed binding mode of A5 was investigated by a docking analysis. These results indicate that compound A5 is a promising lead compound that deserves further investigation.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.