A novel vital sign pattern predicts sepsis-related myocardial injury mortality.

Non-invasive, real-time monitorable indicators for early assessment of sepsis-associated myocardial injury (SMI) are still lacking. We aimed to develop non-invasive, real-time indicators for early assessment of SMI using bedside heart rate (HR) and diastolic arterial pressure (DAP) monitors. In this multi-center cohort study, piece-wise exponential additive mixed models were used to estimate the exposure window and time fraction of the hazardous exposure proportion, and secondarily to analyze the exposure characterization on this basis to identify high-risk exposure pattern. In total, 20,043 patients were finally included; we found that SMI patients had the highest survival rate when HR was <90 bpm or DAP was between 50 and 70 mmHg. Further investigation revealed that the SMI high-risk exposure pattern was the H1D-1 (HR ≥ 90 bpm and DAP ≤ 50 mmHg, exposure proportion > 0.3 and 0.2, respectively, and exposure window on admission day 1). H1D-1 exposure pattern using glucocorticoids significantly increased the risk of mortality in H1D-1. Validation against various methodologies and data sources demonstrated acceptable consistency.

Developing large language models to detect adverse drug events in posts on x.

Adverse drug events (ADEs) are one of the major causes of hospital admissions and are associated with increased morbidity and mortality. Post-marketing ADE identification is one of the most important phases of drug safety surveillance. Traditionally, data sources for post-marketing surveillance mainly come from spontaneous reporting system such as the Food and Drug Administration Adverse Event Reporting System (FAERS). Social media data such as posts on X (formerly Twitter) contain rich patient and medication information and could potentially accelerate drug surveillance research. However, ADE information in social media data is usually locked in the text, making it difficult to be employed by traditional statistical approaches. In recent years, large language models (LLMs) have shown promise in many natural language processing tasks. In this study, we developed several LLMs to perform ADE classification on X data. We fine-tuned various LLMs including BERT-base, Bio_ClinicalBERT, RoBERTa, and RoBERTa-large. We also experimented ChatGPT few-shot prompting and ChatGPT fine-tuned on the whole training data. We then evaluated the model performance based on sensitivity, specificity, negative predictive value, positive predictive value, accuracy, F1-measure, and area under the ROC curve. Our results showed that RoBERTa-large achieved the best F1-measure (0.8) among all models followed by ChatGPT fine-tuned model with F1-measure of 0.75. Our feature importance analysis based on 1200 random samples and RoBERTa-Large showed the most important features are as follows: "withdrawals"/"withdrawal", "dry", "dealing", "mouth", and "paralysis". The good model performance and clinically relevant features show the potential of LLMs in augmenting ADE detection for post-marketing drug safety surveillance.

Efficient caproate production from lignocellulose via single-step electro-fermentation platform without organic electron donor.

Caproate production by microbial fermentation gained the advantages of sustainability and eco-friendliness, but challenged by sterile fermentation environment, necessity of organic electron donors. Here, a single-step electro-fermentation (EF) process of mixed culture was proposed for caprate production from rice straw. At the optimal potential of -0.8 V, caproate concentration, yield and selectivity in the neutral red (NR)-mediated EF system were 2.4 g/L, 0.2 g/g and 26.6%. Long-term operation accumulated 5.3 g/L caproate with the yield and selectivity of 0.2 g/g and 34.2% in the EF+NR system. Bioaugmentation by dosing chain-elongation microbial consortium further improved the caproate production, yield and selectivity to 9.1 g/L, 0.3 g/g and 41.5%, respectively. The improved caproate production in the bioaugmented EF+NR system was likely due to the enhanced interspecies electron transfer, reconstructed microbial community, multiple electron donors and suitable pH environment. Present study offers a feasible strategy for cost-effective caprate production directly from waste biomass.

The effect of Ba Duan Jin exercise intervention on cardiovascular disease: a meta-analysis of randomized controlled trials.

Background: There is a growing interest in the use of complementary therapies for the prevention of disease and the maintenance of health. Furthermore, complementary therapies that incorporate exercise are becoming increasingly prevalent among the older adult, and thus may represent a crucial strategy for the primary and secondary prevention of cardiovascular disease (CVD). Exercise therapy, as a means to prevent and treat cardiovascular diseases, has been gradually applied in clinical practice. It has the advantages of reducing mortality, improving clinical symptoms, restoring physical function and improving quality of life. In recent years, traditional Chinese sports such as Ba Duan Jin and Qigong have developed rapidly. Therefore, a comprehensive systematic review is required to examine interventions involving Ba Duan Jin exercise in healthy adults or those at increased risk of CVD in order to determine the effectiveness of Ba Duan Jin exercise for the primary prevention of CVD. Objective: To investigate the effect of Ba Duan Jin exercise intervention for the primary prevention of cardiovascular diseases. Methods: Eight databases were systematically searched from inception to July, 2024 for randomized controlled trials (RCTs) to evaluated the impact of Ba Duan Jin exercise intervention on cardiovascular diseases. The search terms were "Cardiovascular diseases" "Ba Duan Jin" and "Randomized controlled." The Cochrane risk assessment tool was used to evaluate the study quality, and the meta-analysis was performed using Rev. Man 5.4 software. Results: Seventeen completed trials were conducted with 1,755 participants who were randomly assigned and met the inclusion criteria. All 17 studies were conducted in China. The meta-analysis indicates that Ba Duan Jin exercise therapy can provide long-term benefits (20-30 years) by reducing all-cause mortality (RR = 0.55, 95% CI: 0.44-0.68, p < 0.01) and stroke mortality (RR = 0.49, 95% CI: 0.36-0.66, p < 0.01) in hypertensive patients. Subgroup analyses reveal that Ba Duan Jin exercise therapy decreases SBP (MD = -4.05, 95% CI = -6.84 to -1.26, p < 0.01) and DBP (MD = -3.21, 95% CI = -5.22 to -1.20, p < 0.01) levels in patients with essential hypertension, significantly reduces serum TC (MD = -0.78, 95% CI = -1.06 to -0.50, p < 0.01), TG (MD = -0.78, 95% CI = -0.93 to -0.62, p < 0.01), and LDL-C (MD = -0.76, 95% CI = -0.92 to -0.60, p < 0.01) levels in patients with hyperlipidemia, increases HDL-C (MD = 0.32, 95% CI = 0.14-0.51, p < 0.01) levels, and produces beneficial effects on cardiovascular function. Additionally, it can alleviate anxiety (MD = -3.37, 95% CI = -3.84 to -2.89, p < 0.01) and improve sleep quality (MD = -2.68, 95% CI = -3.63to -1.73, p < 0.01). Conclusion: Ba Duan Jin exercise therapy can improve the physical and mental condition and quality of life of patients with cardiovascular diseases, and it is worthy of further promotion and application in clinical practice. Systematic review registration: PROSPERO, identifier: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024496934.

Shorter Crohn's Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies.

Background and Aims: Early biologic therapy treatment has demonstrated better outcomes in Crohn's disease (CD). We evaluated the impact of CD duration in patients with moderately to severely active CD treated with risankizumab therapy. Methods: This post hoc analysis evaluated clinical, endoscopic, and safety outcomes by baseline CD duration (<2, 2-5, >5-10, and >10 years) in patients from ADVANCE, MOTIVATE, and FORTIFY. Pooled induction analyses included patients who received intravenous 600-mg dose of risankizumab or placebo for 12 weeks. Maintenance analyses included patients who responded to induction risankizumab and received subcutaneous 180-mg or 360-mg dose of risankizumab for 52 weeks. Duration subgroups were compared using Cochrane-Armitage trend tests with nominal P values. Results: Among 527 patients who received risankizumab 600-mg induction therapy, higher outcome rates were observed at week 12 among patients with shorter vs longer baseline disease duration (for <2, 2-5, >5-10, and >10 years, clinical remission: 42.7%, 46.9%, 43.5%, and 33.2% [P = .046]; endoscopic response: 48.3%, 36.3%, 32.0%, and 33.4% [P = .025]). Among 298 patients receiving risankizumab (180 mg or 360 mg) maintenance therapy, shorter vs longer baseline disease duration was generally associated with numerically higher endoscopic outcome rates at week 52. Higher clinical remission and endoscopic outcome rates were generally observed with shorter disease duration with 180-mg risankizumab dose only. Adverse event rates were generally similar across duration subgroups. Conclusion: Clinical benefits of risankizumab are observed across disease duration subgroups; clinical and endoscopic outcome rates are higher with risankizumab initiation earlier in the disease course (ClinicalTrials.gov numbers: NCT03105128, NCT03104413, and NCT03105102).

The non-covalent and covalent interactions of whey proteins and saccharides: influencing factor and utilization in food.

During the application of Whey proteins (WPs), they often have complex interactions with saccharides (Ss), another important biopolymer in food substrate. The texture and sensory qualities of foods containing WPs and Ss are largely influenced by the interactions of WPs-Ss. Moreover, the combination of WPs and Ss is possible to produce many excellent functional properties including emulsifying properties and thermal stability. However, the interactions between WPs-Ss are complex and susceptible to some processing conditions. In addition, with different interaction ways, they can be applied in different fields. Therefore, the non-covalent interaction mechanisms between WPs-Ss are firstly summarized in detail, including electrostatic interaction, hydrogen bond, hydrophobic interaction, van der Waals force. Furthermore, the existence modes of WPs-Ss are introduced, including complex coacervates, soluble complexes, segregation, and co-solubility. The covalent interactions of WPs-Ss in food applications are often formed by Maillard reaction (dry or wet heat reaction) and occasionally through enzyme induction. Then, two common influencing factors, pH and temperature, on non-covalent/covalent bonds are introduced. Finally, the applications of WPs-Ss complexes and conjugations in improving WP stability, delivery system, and emulsification are described. This review can improve our understanding of the interactions between WPs-Ss and further promote their wider application.

Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study.

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

BACKGROUND: Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). AIM: To evaluate the corticosteroid-sparing effect of risankizumab in CD. METHODS: During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid-free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. RESULTS: Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid-free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid-free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid-free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar, regardless of baseline corticosteroid use. CONCLUSIONS: Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid-free clinical and endoscopic outcomes at week 52.

A Hybrid Structure to Improve Electrochemical Performance of SiO Anode Materials in Lithium-Ion Battery.

The wide utilization of lithium-ion batteries (LIBs) prompts extensive research on the anode materials with large capacity and excellent stability. Despite the attractive electrochemical properties of pure Si anodes outperforming other Si-based materials, its unsafety caused by huge volumetric expansion is commonly admitted. Silicon monoxide (SiO) anode is advantageous in mild volume fluctuation, and would be a proper alternative if the low initial columbic efficiency and conductivity can be ameliorated. Herein, a hybrid structure composed of active material SiO particles and carbon nanofibers (SiO/CNFs) is proposed as a solution. CNFs, through electrospun processes, serve as a conductive skeleton for SiO nanoparticles and enable SiO nanoparticles to be uniformly embedded in. As a result, the SiO/CNF electrochemical performance reaches a peak at 20% the mass ratio of SiO, where the retention rate reaches 73.9% after 400 cycles at a current density of 100 mA g-1, and the discharge capacity after stabilization and 100 cycles are 1.47 and 1.84 times higher than that of pure SiO, respectively. A fast lithium-ion transport rate during cycling is also demonstrated as the corresponding diffusion coefficient of the SiO/CNF reaches ~8 × 10-15 cm2 s-1. This SiO/CNF hybrid structure provides a flexible and cost-effective solution for LIBs and sheds light on alternative anode choices for industrial battery assembly.

Pelvic rotation correction combined with Schroth exercises for pelvic and spinal deformities in mild adolescent idiopathic scoliosis: A randomized controlled trial.

INTRODUCTION: Individualized treatment of spinal deformity is needed for adolescent idiopathic scoliosis (AIS), and the integration of pelvic rotation correction based on proprioceptive neuromuscular facilitation (PNF) into regular physiotherapy may be a promising approach. However, few high-quality studies have investigated its effects. This study aimed to evaluate the efficacy of pelvic rotation correction combined with Schroth exercises in the treatment of mild AIS. METHODS: This was a randomized controlled trial. Forty-two AIS patients were randomly divided into experimental and control groups. Both groups underwent 20 therapeutic sessions over 24 weeks. All patients (n = 42) performed Schroth exercises at each session. In addition, the experimental group (n = 21) also participated in a pelvic rotation correction program based on PNF at each session. The primary outcome was the concave/convex ratio of hipbone widths, and the secondary outcomes included the Cobb angle, trunk rotation angle, self-perception, apical vertebral translation, and apical vertebral rotation. Patients were evaluated before and after 24 weeks of intervention. RESULTS: There was a significant between-group difference in the change from baseline between the experimental and control groups for the following parameters: concave/convex ratio 2.89% (95% confidence interval [CI], 1.58 to 4.20, P<0.001), trunk rotation angle -1.26° (95% CI, -2.20 to -0.32; P = 0.01), and apical vertebral rotation improved by at least one class from baseline in 3 patients (14.3%) in the control group and 9 patients (42.9%) in the experimental group (P = 0.04). While Cobb angle -1.60° (95% CI, -7.75 to 0.54; P = 0.14), self-image 0.149 (95% CI, 0.001 to 0.297; P = 0.049), apical vertebral translation -0.58 mm (95% CI, -3.83 to 2.67; P = 0.72), and pelvic obliquity 0.10° (95% CI, -0.21 to 0.41; P = 0.52) did not differ significantly. CONCLUSIONS: Pelvic rotation correction combined with Schroth exercises more effectively improved pelvic axial rotation and other spinal deformities, including trunk rotation and apical vertebral rotation, than Schroth exercises alone in the treatment of mild AIS.

Dapagliflozin attenuates AKI to CKD transition in diabetes by activating SIRT3/PGC1-α signaling and alleviating aberrant metabolic reprogramming.

BACKGROUND: Patients with diabetes are prone to acute kidney injury (AKI) with a high mortality rate, poor prognosis, and a higher risk of progression to chronic kidney disease than non-diabetic patients. METHODS: Streptozotocin (STZ)-treated type 1 and db/db type 2 diabetes model were established, AKI model was induced in mice by ischemia-reperfusion injury(IRI). Mouse proximal tubular cell cells were subjected to high glucose and hypoxia-reoxygenation in vitro. Transcriptional RNA sequencing was performed for clustering analysis and target gene screening. Renal structural damage was determined by histological staining, whereas creatinine and urea nitrogen levels were used to measure renal function. RESULTS: Deteriorated renal function and renal tissue damage were observed in AKI mice with diabetic background. RNA sequencing showed a decrease in fatty acid oxidation (FAO) pathway and an increase in abnormal glycolysis. Treatment with Dapa, Sitagliptin(a DPP-4 inhibitor)and insulin reduced blood glucose levels in mice, and improved renal function. However, Dapa had a superior therapeutic effect and alleviated aberrant FAO and glycosis. Dapa reduced cellular death in cultured cells under high glucose hypoxia-reoxygenation conditions, alleviated FAO dysfunction, and reduced abnormal glycolysis. RNA sequencing showed that SIRT3 expression was reduced in diabetic IRI, which was largely restored by Dapa intervention. 3-TYP, a SIRT3 inhibitor, reversed the renal protective effects of Dapa and mediated abnormal FAO and glycolysis in mice and tubular cells. CONCLUSION: Our study provides experimental evidence for the use of Dapa as a means to reduce diabetic AKI by ameliorating metabolic reprogramming in renal tubular cells.

Beneficial In Vitro Effects of Polysaccharide and Non-Polysaccharide Components of Dendrobium huoshanense on Gut Microbiota of Rats with Type 1 Diabetes as Opposed to Metformin.

The extract of Dendrobium huoshanense, a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and antioxidant effects. In this study, the direct effects of polysaccharide (DHP) and non-polysaccharide (NDHP) components of D. huoshanense, as well as its water extract (DHWE) were compared with that of metformin (an antidiabetic drug) on the gut microbiota (collected from fecal flora) of rats with streptozotocin-induced type 1 diabetes (T1D) using an in vitro fermentation method. The results showed that DHWE, DHP, and NDHP reduced pH and increased bacterial proliferation and short-chain fatty acid (SCFA) content in fermentation broth. DHWE, DHP, NDHP and metformin promoted the production of acetic and propionic acid, acetic acid, propionic acid and butyric acid, and propionic acid, respectively. DHWE, DHP, and NDHP reduced the abundance of Proteobacteria (subdominant pathogenic bacteria) and increased the abundance of Firmicutes (dominant beneficial gut bacteria). NDHP also reduced the abundance of Bacteroidetes (beneficial and conditional pathogenic). Metformin increased the abundance of Proteobacteria and reduced the abundance of Firmicutes and Bacteroidetes. At the genus level, NDHP promoted the proliferation of Megamonas and Megasphaera and decreased harmful bacteria (e.g., Klebsiella), and DHP increased the abundance of Prevotellaceae (opportunistic and usually harmless). By contrast, metformin increased the abundance of harmful bacteria (e.g., Citrobacter) and reduced the abundance of beneficial bacteria (e.g., Oscillospira). Our study indicates that DHWE, DHP, and NDHP are potentially more beneficial than metformin on the gut microbiota of T1D rats in vitro.

Type-printable photodetector arrays for multichannel meta-infrared imaging.

Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells.

BACKGROUND: Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer. METHODS: In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells. RESULTS: We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway. CONCLUSION: Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.

PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis.

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.

Exploration of the Existence Forms and Patterns of Dissolved Oxygen Molecules in Water.

The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.

Division of Main Geological and Engineering Controlling Types of Low-Production Coalbed Methane Well-Blocks and their Stimulation Measures.

At present, the identification of the main factors controlling low-production coalbed methane (CBM) wells and production enhancement measures does not consider geological and reservoir differences between individual wells and the CBM production effect of well groups simultaneously. In view of this, an evaluation index system suitable for use on inefficient well-blocks was established, which involves their geological resource potential, ground stress, coal structure, and comprehensive permeability under engineering influences from a systemic perspective. The main geological engineering types were determined by zoning superposition, and the corresponding stimulation measures were proposed. The evaluation results of the Shizhuang South Block in the Qinshui Basin show that the area of interest can be divided into Class I, II, and III potential areas, of which the Class II potential areas are subdivided into six blocks. In Zone I, the horizontal well infill method is preferred to increase the CBM production from well groups. At the current level of technology, it is difficult to gain economic benefits from Zone III. In Zone II, these stimulation measures such as the infilling method of staged fracturing horizontal wells, refracturing under supplementary injection holes, roof fracturing, the combined method of acidification and secondary fracturing or nitrogen injection and secondary fracturing, the combined method of acidification and controlled displacement secondary fracturing, and controlled displacement repetitive roof fracturing, among others, can be adopted.

An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Jeotgalibacillus haloalkalitolerans sp. nov., a novel alkalitolerant and halotolerant bacterium, isolated from the confluence of the Fenhe River and the Yellow River.

A Gram-stain positive, aerobic, alkalitolerant and halotolerant bacterium, designated HH7-29 T, was isolated from the confluence of the Fenhe River and the Yellow River in Shanxi Province, PR China. Growth occurred at pH 6.0-12.0 (optimum, pH 8.0-8.5) and 15-40℃ (optimum, 32℃) with 0.5-24% NaCl (optimum, 2-9%). The predominant fatty acids (> 10.0%) were iso-C15:0 and anteiso-C15:0. The major menaquinones were MK-7 and MK-8. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that strain HH7-29 T was a member of the genus Jeotgalibacillus, exhibiting high sequence similarity to the 16S rRNA gene sequences of Jeotgalibacillus alkaliphilus JC303T (98.4%), Jeotgalibacillus salarius ASL-1 T (98.1%) and Jeotgalibacillus alimentarius YKJ-13 T (98.1%). The genomic DNA G + C content was 43.0%. Gene annotation showed that strain HH7-29 T had lower protein isoelectric points (pIs) and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt and alkali. The average nucleotide identity, digital DNA-DNA hybridization values, amino acid identity values, and percentage of conserved proteins values between strain HH7-29 T and its related species were 71.1-83.8%, 19.5-27.4%, 66.5-88.4% and 59.8-76.6%, respectively. Based on the analyses of phenotypic, chemotaxonomic, phylogenetic and genomic features, strain HH7-29 T represents a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus haloalkalitolerans sp. nov. is proposed. The type strain is HH7-29 T (= KCTC 43417 T = MCCC 1K07541T).