Active strong coupling of exciton and nanocavity based on GSST-WSe2 hybrid nanostructures.

The strong coupling between optical resonance microcavity and matter excitations provides a practical path for controlling light-matter interactions. However, conventional microcavity, whose functions are fixed at the fabrication stage, dramatically limits the modulation of light-matter interactions. Here, we investigate the active strong coupling of resonance mode and exciton in GSST-WSe2 hybrid nanostructures. It is demonstrated that significant spectral splitting is observed in single nanostructures, tetramers, and metasurfaces. We further confirm the strong coupling by calculating the enhanced fluorescence spectra. The coupling effect between the excited resonance and exciton is dramatically modulated during the change of GSST from amorphous to crystalline, thus realizing the strong coupling switching. This switching property has been fully demonstrated in several systems mentioned earlier. Our work is significant in guiding the study of actively tunable strong light-matter interactions at the nanoscale.

Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.

Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.

Enhancement of vitamin B6 production driven by omics analysis combined with fermentation optimization.

BACKGROUND: Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B6 for various applications. Numerous microorganisms naturally produce vitamin B6, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B6 poses a challenge in constructing an efficient cell factory. RESULTS: In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B6, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation. CONCLUSION: Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B6 in the future.

Metabolic Traits and Risk of Ischemic Stroke in Japanese and European Populations: A Two-Sample Mendelian Randomization Study.

The role of metabolic traits in ischemic stroke (IS) has been explored through observational studies and a few Mendelian randomization (MR) studies employing limited methods in European populations. This study aimed to investigate the causal effects of metabolic traits on IS in both East Asian and European populations utilizing multiple MR methods based on genetic insights. Two-sample and multivariable MR were performed, and MR estimates were calculated as inverse-variance weighted (IVW), weighted median, and penalized weighted median. Pleiotropy was assessed by MR-Egger and Mendelian randomization pleiotropy residual sum and outlier tests. Systolic blood pressure (SBP) was associated with an increased risk of IS by IVW in both European (ORIVW: 1.032, 95% CI: 1.026-1.038, p < 0.001) and Japanese populations (ORIVW: 1.870, 95% CI: 1.122-3.116, p = 0.016), which was further confirmed by other methods. Unlike the European population, the evidence for the association of diastolic blood pressure (DBP) with IS in the Japanese population was not stable. No evidence supported an association between the other traits and IS (all Ps > 0.05) in both races. A positive association was found between SBP and IS in two races, while the results of DBP were only robust in Europeans.

Multiple Cofactor Engineering Strategies to Enhance Pyridoxine Production in Escherichia coli.

Pyridoxine, also known as vitamin B6, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in optimizing its production through microbial biosynthesis. However, an imbalance in the net production of NADH disrupts intracellular cofactor levels, thereby limiting the efficient synthesis of pyridoxine. In our study, we focused on multiple cofactor engineering strategies, including the enzyme design involved in NAD+-dependent enzymes and NAD+ regeneration through the introduction of heterologous NADH oxidase (Nox) coupled with the reduction in NADH production during glycolysis. Finally, the engineered E. coli achieved a pyridoxine titer of 676 mg/L in a shake flask within 48 h by enhancing the driving force. Overall, the multiple cofactor engineering strategies utilized in this study serve as a reference for enhancing the efficient biosynthesis of other target products.

Emodin Attenuates Sepsis-induced Intestinal Injury by Regulating TRPM7 Expression.

Background: Sepsis is a potentially lethal organ immune dysfunction induced by infection, with the stomach being the first organ to be attacked. Emodin has anti-inflammatory and gastrointestinal functions, but its therapeutic effect on intestinal injury in sepsis remains unclear. This study sought to investigate the role of emodin in treating intestine damage brought on by sepsis. Methods: Between June 2021 and July 2023, Lipopolysaccharide (LPS) was used to stimulate human intestinal epithelial cells NCM460 to create a septic cell model, and treatment was regulated by rhodopsin. Transient receptor potential melastatin 7 (TRPM7) expression was used to check that the LPS induction conditions were acceptable. About the proliferation of the NCM460 cells, the effects of overexpressing TRPM7 and silencing TRPM7 were assessed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide test. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 expression in the cells was detected using enzyme-linked immunosorbent assays. TRPM7 messenger RNA expression was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Western blot determined the levels of TRPM7, Bcl2-associated X (Bax), and B-cell lymphoma-2 (Bcl2) protein expression levels. The terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) technique was used to measure the apoptosis rate. Results: The levels of the inflammatory factors and Bax expression in the cells and the cell apoptosis rate steadily increased as the LPS-induced concentration increased. In contrast, cell viability and the Bcl2 expression levels gradually decreased. In this study, we treated the cells with LPS at a concentration of 25 µg/mL for 12 hours. It was detected that the knockdown of TRPM7 expression decreased the effect of LPS induction, while boosting the expression of TRPM7 boosted the effectiveness. Treatment with emodin lowered TRPM7 expression, increasing cell survival, and Bcl2 expression levels while decreasing the apoptosis rate, inflammatory factors, and Bax expression levels. Conclusion: Emodin may alleviate sepsis-induced intestinal injury by down-regulating the TRPM7 gene. These findings suggest that emodin may hold promise as a therapeutic agent for treating intestinal injury in sepsis. If further validated through additional research and clinical trials, emodin or similar compounds could potentially be developed into safe and effective medications for sepsis patients.

Bioinformatics and Functional Analysis of OsASMT1 Gene in Response to Abiotic Stress.

The study aimed to elucidate the functional characteristics of OsASMT1 gene under copper (Cu) or sodium chloride (NaCl) stress. Bioinformatics scrutiny unveiled that OsASMT1 is situated on chromosome 9. Its protein architecture, comprising dimerization and methyltransferase domains, showed significant similarities to OsASMT2 and OsASMT3. High expression in roots and panicles, along with abiotic stress putative cis-regulatory elements in the promoter, indicated potential stress responsiveness. Real-time quantitative PCR confirmed OsASMT1 induction under Cu and NaCl stress in rice. Surprisingly, yeast expressing OsASMT1 did not exhibit enhanced resistance to abiotic stresses. The results of subcellular localization analysis indicated that OsASMT1 plays a role in the cytoplasm. While OsASMT1 responded to Cu and NaCl stress in rice, its heterologous expression in yeast failed to confer abiotic stress resistance, highlighting the need for further investigation of its functional implications.

Leukocyte counts and ratios as potential predictors of large vessel occlusion in acute ischemic stroke: A retrospective cohort study.

Leukocyte counts and ratios are independent biomarkers to determine the severity and prognosis of acute ischemic stroke (AIS). In AIS, the connection between leukocytes and large vessel occlusion (LVO) is uncertain. This study aims to determine the relationship between the existence of LVO and leukocyte counts and ratios on admission to AIS. Patients were retrospectively evaluated within six hours of AIS starting between January 2019 and April 2023. On admission, blood specimens were collected, and leukocyte subtype counts were promptly analyzed. Computed tomography or digital subtraction angiography were utilized to verify the existence of LVO. Regression analysis and receiver operating characteristic (ROC) curves were employed to investigate the connections between the counts and ratios of leukocytes and the existence of LVO, as well as the discriminatory ability of these variables in predicting LVO. Total white blood cell (WBC) count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) were substantially higher in the LVO existence group compared to the LVO absence group, whereas the ratio of eosinophils to neutrophils (ENR × 102) was lower (P < .001, respectively). Significant associations were observed between total WBC counts, neutrophil counts, NLR, and ENR × 102 and the existence of LVO (P < .001, respectively). Total WBC counts, neutrophil counts, NLR, and ENR × 102 had respective areas under the curves (AUC) of 0.730, 0.748, 0.704, and 0.680 for identifying LVO. Our results show that in AIS patients, the existence of LVO is independently associated with elevated total WBC and neutrophil counts, high NLR, and low ENR × 102 levels. Neutrophil and total WBC counts, as well as NLR and levels of ENR × 102, may serve as potential biomarkers for predicting LVO. Neuroinflammation, based on the existence of LVO, should be given particular attention in future investigations.

Differentiation of isomeric chalcone and dihydroflavone using liquid chromatography coupled with hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS): An application for flavonoids-focused characterization of Snow chrysanthemum.

Although the co-occurrences of isomeric chalcones and dihydroflavones widely appear in medicinal plants, the differentiation of such isomerism seldom succeeds using MS/MS, attributing to totally identical MS/MS spectra. Here, efforts were paid to pursue an eligible tool allowing to address the technical challenge. Being inspired by that one more proton signal is observed in 1H NMR spectrum of isoliquiritigenin than liquiritigenin when employing DMSO­d6 as solvent, hydrogen-deuterium exchange (HDX)-MS/MS was evaluated towards differentiating isomeric chalcones and dihydroflavones through replacing H2O with D2O to prepare the mobile phase. As a result, differences were observed for either MS1 or MS2 spectrum when comparing two pairs of isomers, such as liquiritigenin vs. isoliquiritigenin and liquiritin vs. isoliquiritin, because the isomeric precursor and fragment ion species owned different amounts of hydroxyl protons and those reactive protons could be partially or completely substituted by deuterium protons at the exposure in D2O to result in n × 1.006 mass increments. Moreover, utmost four hydrogen/deuterium exchanges occurred for a single glucosyl moiety. Thereafter, HDX-MS/MS was applied to characterize the flavonoids of Snow chrysanthemum, a precious edible herbal medicine that is rich in isomeric chalcones and dihydroflavones. Through paying special attention to the deuterium labeling styles of (de)protonated molecules as well as those featured fragment ions, five pairs of isomeric chalcones and dihydroflavones were confirmatively differentiated, in addition to that 28 flavonoids were structurally annotated by applying those well-defined mass fragmentation rules. Hence, this study offered an in-depth insight towards the flavonoids-focused characterization of Snow chrysanthemum, and more importantly, HDX-MS/MS is a superior tool to differentiate, but not limited to, isomeric chalcones and dihydroflavones.

Reference Standards of Cardiorespiratory Fitness Measured With the Cardiopulmonary Exercise Test Using the Treadmill in Chinese Adults Younger Than 60 Years.

PURPOSE: Cardiorespiratory fitness (CRF) is a strong predictor of cardiorespiratory diseases and varies by race. The purpose of this study was to provide CRF reference standards and a prediction equation for peak oxygen uptake (V˙O 2peak ) from treadmill-based cardiopulmonary exercise testing (CPX) in Chinese individuals. METHODS: Healthy participants (n = 4199) who completed a CPX using a treadmill were studied. The percentiles of V˙O 2peak were determined for four age groups (decades). A regression prediction model was developed from the derivation cohort (n = 3361), validated in the independent validation cohort (n = 838), and compared with the widely used Wasserman equation and the Fitness Registry and the Importance of Exercise National Database (FRIEND) equation. RESULTS: The mean V˙O 2peak values of four age groups (20-29, 30-39, 40-49, and 50-59 yr) were 42.6, 41.2, 38.7, and 35.9 mL/kg/min, respectively, for men, and 37.1, 34.7, 32.0, and 30.3 mL/kg/min, respectively, for women. The 50th percentiles of relative V˙O 2peak decreased with age for both sexes. The prediction equation was: Absolute V˙O 2peak (mL/min) = 236.68 - (504.64 × sex [male = 0; female = 1]) + (21.23× weight [kg]) - (14.31 × age [yr]) + (9.46 × height [cm]) (standard error of the estimate = 379.59 mL/min, R2 = 0.66, P < .001).Percentage predicted V˙O 2peak for the validation sample was 100.2%. The novel equation performed better than the other two equations. CONCLUSION: This study reports the first CRF reference standards and prediction equation generated from treadmill CPX in China. These reference standards provide a framework for interpreting the CRF of the Chinese population and could be useful information for a global CRF database.

[Determination of nine aromatic amines in water by cloud point extraction-gas chromatography-mass spectrometry].

Aromatic amines are a class of compounds bearing amino groups on their benzene rings; these compounds are important raw materials for the industrial production of rubber chemicals, pesticides, dyes, pharmaceuticals, photosensitive chemicals, and agricultural chemicals. Research has revealed that some aromatic amines teratogenetic, carcinogenic, and mutagenic properties. Given the high toxicity and potential harm caused by aromatic amines, monitoring their levels in water sources is critical. Aromatic amines are among the 14 strategic environmental pollutants blacklisted in China, and assessing their exposure levels is essential for protecting human health and the environment. At present, the standard method for detecting aromatic amines in water is liquid-liquid extraction-gas chromatography-mass spectrometry (LLE-GC-MS). However, this method has the disadvantages of large sample size requirement, complex operation, long analysis time, and high reagent consumption. In this study, instead of traditional LLE technology, cloud point extraction (CPE) technology was used in combination with GC-MS to establish an efficient, sensitive, and environment-friendly method for the detection of nine aromatic amines, namely, 2-chloramine, 3-chloramine, 4-chloramine, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 1-naphthylamine, 2-naphthylamine, and 4-aminobenzene, in water. Triton X-114 was used as the extraction agent. The main experimental parameters were optimized using a single-factor optimization method. The aromatic amines in various water samples were quantitatively analyzed using GC-MS. The nine aromatic amines were separated on a DB-35 MS capillary column (30 m×0.25 mm×0.25 µm). The mass spectrometer was operated in selected ion monitoring (SIM) mode, and quantitative analysis was performed using the internal standard method. The results demonstrated that all nine aromatic amines could be completely separated within 16 min and had good linearities within accurate mass concentration ranges, with correlation coefficients (R2) greater than 0.998. The limits of detection (LODs) and quantification (LOQs) of these aromatic amines in water were 0.12-0.48 and 0.40-1.60 µg/L, respectively. The accuracy and precision of the method were assessed via the determination of aromatic amines in surface water of drinking water sources, offshore seawater, wastewater of the typical printing and dyeing industry at levels of 2.0 and 10.0 µg/L. The recoveries of the aromatic amines in surface water of drinking water sources were 81.1%-109.8%, with intra-day and inter-day relative standard deviations (RSDs) of 0.7%-5.2% (n=6) and 1.6%-6.2% (n=3), respectively. The recoveries of the aromatic amines in offshore seawater were 83.0%-115.8%, with intra-day RSDs (n=6) of 1.5%-8.6% and inter-day RSDs (n=3) of 2.4%-12.2%. The recoveries of the nine aromatic amines in wastewater of the typical printing and dyeing industry were 91.0%-120.0%, with intra-day RSDs (n=6) of 2.9%-12.9% and inter-day RSDs (n=3) of 2.5%-13.1%. The established method was used to detect nine aromatic amines in actual water samples. No aromatic amines were detected in the surface water of drinking water sources or offshore seawater samples. However, 2-chloramine, 4-chloramine, and 4-aminobenzene, which are frequently used in the printing and dyeing industry, were detected in the wastewater of the typical printing and dyeing industry samples. The proposed method offers the advantages of simple operation, high sensitivity, low cost, low organic reagent requirement, and good repeatability. Thus, this method provides reliable technical support for studying the residual status and environmental behavior of aromatic amines in water.

The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants.

Introduction: Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: We included 440,551 participants from the UK Biobank between the baseline visit (2006-2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality. Results: During a median follow-up of 13.74 years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93-0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90-0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34-1.36), CVD-specific (HR: 1.47, 95% CI: 1.44-1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20-1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality. Conclusions: Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00355-7.

Soil nitrogen cycling gene abundances in response to organic amendments: A meta-analysis.

Quantification of nitrogen (N) cycling genes contributes to our best understanding of N transformation processes. The application of organic amendment (OA) is widely recognized as an effective measure to improve N management and soil fertility in various ecosystems. However, our understanding of N-cycling gene abundances in response to OA application remains deficient. We performed a meta-analysis embracing 124 sets of observation data to study the impact of OA application on the main N-cycling gene abundances, including nifH, amoA, nirS, nirK and nosZ. We found that the significantly positive response of N-cycling gene abundances to OA application was attributed to the rotation cropping system (by 6.45 %-104.20 %) in the field experiment (by 19.43 %-52.56 %), OA application alone (by 8.29 %-111.70 %) especially manure addition (by 33.43 %-98.70 %), application dose of OAs within 10-20 t ha-1 (by 45.33 %-381.90 %), fertilization duration <5 years (by 43.69 %-112.63 %), C/N of OA <25 (by 37.87 %-160.90 %), SOC lower than 1.2 % (by 41.44 %-157.89 %) and application to alkaline soil (by 32.24 %-134.40 %). Moreover, soil organic carbon (SOC) and pH were the most essential regulators associated with N-cycling gene abundances with OA application. Identification of key driving factors of the abundance of N-cycling functional genes will help remedy strategies for managing OAs in ecosystems.

Patterns of antibiotic administration in Chinese neonates: results from a multi-center, point prevalence survey.

OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Accelerating drug development for amyotrophic lateral sclerosis: construction and application of a disease course model using historical placebo group data.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an irreversible degenerative disease. Placebo-controlled randomized trials are currently the main trial design to assess the clinical efficacy of drugs for ALS treatment. The aim of this study was to establish models to quantitatively describe the course of ALS, explore influencing factors, and provide the necessary information for ALS drug development. METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library Central Register for placebo-controlled trials that evaluated treatments for ALS. From these trials, we extracted the clinical and demographic characteristics of participants in the placebo group, as well as outcome data, which encompassed overall survival (OS) and Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores, at various time points. RESULTS: In total, 47 studies involving 6118 participants were included. Disease duration and the proportion of patients receiving riluzole were identified as significant factors influencing OS in the placebo group. Specifically, the median OS was 35.5 months for a disease duration of 9 months, whereas it was 20.0 months for a disease duration of 36 months. Furthermore, for every 10% increase in the proportion of patients treated with riluzole (100 mg daily), there was an association with a median OS extension of approximately 0.4 months. The estimated time for the ALSFRS-R score in the placebo group to decrease to 50% of its maximum effect from baseline level was approximately 17.5 months, and the time to reach a plateau was about 40 months. CONCLUSIONS: The established disease course model of the historical placebo group is valuable in the decision-making process for the clinical development of ALS drugs. It serves not only as an external control to evaluate the efficacy of the tested drug in single-arm trials but also as prior information that aids in accurately estimating the posterior distribution of the disease course in the placebo group during small-sample clinical trials.

Study on the Hydrogen Effect and Interface/Border Traps of a Depletion-Mode AlGaN/GaN High-Electron-Mobility Transistor with a SiNx Gate Dielectric at Different Temperatures.

In this study, the electrical characteristics of depletion-mode AlGaN/GaN high-electron-mobility transistors (HEMTs) with a SiNx gate dielectric were tested under hydrogen exposure conditions. The experimental results are as follows: (1) After hydrogen treatment at room temperature, the threshold voltage VTH of the original device was positively shifted from -16.98 V to -11.53 V, and the positive bias of threshold was 5.45 V. When the VDS was swept from 0 to 1 V with VGS of 0 V, the IDS was reduced by 25% from 9.45 A to 7.08 A. (2) Another group of original devices with identical electrical performance, after the same duration of hydrogen treatment at 100 °C, exhibited a reverse shift in threshold voltage with a negative threshold shift of -0.91 V. The output characteristics were enhanced, and the saturation leakage current was increased. (3) The C-V method and the low-frequency noise method were used to investigate the effect of hydrogen effect on the device interface trap and border trap, respectively. It was found that high-temperature hydrogen conditions can passivate the interface/border traps of SiNx/AlGaN, reducing the density of interface/border traps and mitigating the trap capture effect. However, in the room-temperature hydrogen experiment, the concentration of interface/border traps increased. The research findings in this paper provide valuable references for the design and application of depletion-mode AlGaN/GaN HEMT devices.

Integrated post-acquisition data processing strategy for rapid steroid sulfate characterization in Toad gall-bladder.

LC-MS serves as a workhorse for chemical profile characterization of Chinese medicinal materials (CMMs) attributing to the ability of measuring fruitful MS/MS spectral information. However, it is laborious to extract the information belonging to the compounds-of-interest from the massive data matrixes even employing those well-defined post-acquisition data processing strategies. Here, efforts were devoted to propose an integrated strategy allowing rapid chemical homologs-focused data filtering through integrating the fit-for-purpose existing strategies, such as molecular weight imprinting (MWI), diagnostic fragment ion filtering (DFIF), neutral loss filtering (NLF), and isotope pattern filtering (IPF). Homologs-focused chemical characterization of a precious CMM namely Toad gall-bladder (Chinese name: Chandan) that is rich of diverse effective steroid sulfates, particularly bufogenin sulfates, bile acid sulfates and bilichol sulfates, was employed as a proof-of-concept. Recombinant human SULT2A1-catalyzed in vitro metabolism was undertaken to generate eight bufogenin sulfates to facilitate summarizing MS/MS spectral behaviors. After in-house data library construction and MS1 and MS2 spectral acquisition, data filtering was conducted as follows: 1) MWI and IPF was utilized in combination to capture deprotonated molecular ions and the 34S isotopic ions for the sulfates of those reported steroids; 2) m/z 79.9568 (SO3-·) and 96.9596 (HSO4-) were applied to DFIF; and 3) SO3 (79.9568 Da) served as the feature to achieve NLF. Those captured MS/MS information subsequently participated in tentatively structural annotation through applying those empirical mass fragmentation rules. As a result, 71 compounds including 7 bufogenin sulfates, 17 bile acid sulfates, 13 bilichol sulfates and a C-23 steroid sulfate were detected from Toad gall-bladder and thereof, 39 ones received plausible identities assignment. Above all, the steroid sulfates in Toad gall-bladder were profiled in depth, and more importantly, the proposed strategy should be a meaningful option for, but not limited to, submetabolome characterization in CMMs.