Search

Abstract In this study, the seismic performance of an ancient pagoda with significant historical and cultural values in China is upgraded by using overall friction pendulum bearing (OFPB) seismic isolation technology, This technique can be used to isolate the pagoda without damaging it. By implementing the OFPB seismic isolation retrofit on the pagoda and comparing and analyzing it with the unretrofitted seismic model, the response of the pagoda under the action of nine seismic waves of three types, namely, near-field earthquakes, far-field earthquakes, and common earthquakes, is investigated. The results show that the OFPB seismic isolation technique significantly reduces the seismic response of the ghats, in which the acceleration amplification factor is reduced by a maximum of 82.46%, the inter-story displacement is reduced by a maximum of 85.15%, and the base shear force is reduced by a maximum of 96.76%. In addition, the tensile damage of the ghats with OFPB seismic isolation was significantly controlled. While the model without seismic isolation has serious damage under the same seismic action and even faces the risk of collapse. The results of the study confirm that the OFPB seismic isolation technology plays a key role in improving the seismic performance of the tower, which is of great theoretical and practical significance to the protection of the tower, and provides an effective technical way for the protection of the tower in the seismic-prone areas.

Abstract In eukaryotes, the leading strand DNA is synthesized by Polε and the lagging strand by Polδ. These replicative polymerases have higher processivity when paired with the DNA clamp PCNA. While the structure of the yeast Polε catalytic domain has been determined, how Polε interacts with PCNA is unknown in any eukaryote, human or yeast. Here we report two cryo-EM structures of human Polε–PCNA–DNA complex, one in an incoming nucleotide bound state and the other in a nucleotide exchange state. The structures reveal an unexpected three-point interface between the Polε catalytic domain and PCNA, with the conserved PIP (PCNA interacting peptide)-motif, the unique P-domain, and the thumb domain each interacting with a different protomer of the PCNA trimer. We propose that the multi-point interface prevents other PIP-containing factors from recruiting to PCNA while PCNA functions with Polε. Comparison of the two states reveals that the finger domain pivots around the [4Fe-4S] cluster-containing tip of the P-domain to regulate nucleotide exchange and incoming nucleotide binding.

Abstract Background Microbial anaerobic metabolism is a key driver of biogeochemical cycles, influencing ecosystem function and health of both natural and engineered environments. However, the temporal dynamics of the intricate interactions between microorganisms and the organic metabolites are still poorly understood. Leveraging metagenomic and metabolomic approaches, we unveiled the principles governing microbial metabolism during a 96-day anaerobic bioreactor experiment. Results During the turnover and assembly of metabolites, homogeneous selection was predominant, peaking at 84.05% on day 12. Consistent dynamic coordination between microbes and metabolites was observed regarding their composition and assembly processes. Our findings suggested that microbes drove deterministic metabolite turnover, leading to consistent molecular conversions across parallel reactors. Moreover, due to the more favorable thermodynamics of N-containing organic biotransformations, microbes preferentially carried out sequential degradations from N-containing to S-containing compounds. Similarly, the metabolic strategy of C18 lipid-like molecules could switch from synthesis to degradation due to nutrient exhaustion and thermodynamical disadvantage. This indicated that community biotransformation thermodynamics emerged as a key regulator of both catabolic and synthetic metabolisms, shaping metabolic strategy shifts at the community level. Furthermore, the co-occurrence network of microbes-metabolites was structured around microbial metabolic functions centered on methanogenesis, with CH4 as a network hub, connecting with 62.15% of total nodes as 1st and 2nd neighbors. Microbes aggregate molecules with different molecular traits and are modularized depending on their metabolic abilities. They established increasingly positive relationships with high-molecular-weight molecules, facilitating resource acquisition and energy utilization. This metabolic complementarity and substance exchange further underscored the cooperative nature of microbial interactions. Conclusions All results revealed three key rules governing microbial anaerobic degradation. These rules indicate that microbes adapt to environmental conditions according to their community-level metabolic trade-offs and synergistic metabolic functions, further driving the deterministic dynamics of molecular composition. This research offers valuable insights for enhancing the prediction and regulation of microbial activities and carbon flow in anaerobic environments. Video Abstract

Abstract Quantitative structure–property relationships have been extensively studied in the field of predicting retention times in liquid chromatography (LC). However, making transferable predictions is inherently complex because retention times are influenced by both the structure of the molecule and the chromatographic method used. Despite decades of development and numerous published machine learning models, the practical application of predicting small molecule retention time remains limited. The resulting models are typically limited to specific chromatographic conditions and the molecules used in their training and evaluation. Here, we have developed a comprehensive dataset comprising over 10,000 experimental retention times. These times were derived from 30 different reversed-phase liquid chromatography methods and pertain to a collection of 343 small molecules representing a wide range of chemical structures. These chromatographic methods encompass common LC setups for studying the retention behavior of small molecules. They offer a wide range of examples for modeling retention time with different LC setups.

Abstract Purpose The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD. Methods We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP). Results In univariate analyses, higher genetically predicted lower birthweight (ORIVW = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( ORIVW = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (ORIVW = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared. Conclusion For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.

Abstract Background Interprofessional education (IPE) has the potential to shape students’ collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. Methods Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson’s correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. Results Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p

Objective As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load‐bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. Methods This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck‐shaft angle (NSA), the angle between the PCT‐axis and the head–neck axis (α), the distance from the femoral head center to the PCT‐axis (δ), and the lengths of the PCT's bottom and top boundaries (L‐bottom and L‐top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t‐test or Mann–Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. Results PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = −0.689, p

Abstract Background This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. Methods PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. Results This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. Conclusions Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients’ conditions and urologists’ acquaintance.

Abstract In recent years, the widespread adoption of wireless sensor networks (WSN) has resulted in the growing integration of the internet of things (IoT). However, WSN encounters limitations related to energy and sensor node lifespan, making the development of an efficient routing protocol a critical concern. Cluster technology offers a promising solution to this challenge. This study introduces a novel cluster routing protocol for WSN. The system selects cluster heads and relay nodes utilizing the multi-strategy fusion snake optimizer (MSSO) and employs the minimum spanning tree algorithm for inter-cluster routing planning, thereby extending the system’s lifecycle and conserving network energy. In pursuit of an optimal clustering scheme, the paper also introduces tactics involving dynamic parameter updating, adaptive alpha mutation, and bi-directional search optimization within MSSO. These techniques significantly increase the algorithm convergence speed and expand the available search space. Furthermore, a novel efficient clustering routing model for WSN is presented. The model generates different objective functions for selecting cluster heads and relay nodes, considering factors such as location, energy, base station distance, intra-cluster compactness, inter-cluster separation, and other relevant criteria. When selecting cluster heads, the fuzzy c-means (FCM) algorithm is integrated into MSSO to improve the optimization performance of the algorithm. When planning inter-cluster routing, the next hop node is selected for the relay node based on distance, residual energy, and direction.The experimental results demonstrate that the proposed protocol reduces energy consumption by at least 26.64% compared to other cluster routing protocols including LEACH, ESO, EEWC, GWO, and EECHS-ISSADE. Additionally, it increases the network lifetime of WSN by at least 25.84%, extends the stable period by at least 52.43%, and boosts the network throughput by at least 40.99%.

Introduction: The purpose of this study was to investigate the association of central lean mass distribution with the risk of mortality. Methods: This cohort study included 40,283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, with the risk of mortality. Results: The median age of the participants was 65 years, and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95% CI: 1.23–1.94), 1.69 (95% CI: 1.26–2.26), and 1.14 (95% CI: 0.72–1.80) for all-cause, cancer, and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI: 3.3%–40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. Conclusion: Trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging and poor diet quality to further increase the risk of death.

Abstract Extractive document summary is usually seen as a sequence labeling task, which the summary is formulated by sentences from the original document. However, the selected sentences usually are high redundancy in semantic space, so that the composed summary are high semantic redundancy. To alleviate this problem, we propose a model to reduce the semantic redundancy of summary by introducing the cluster algorithm to select difference sentences in semantic space and we improve the base BERT to score sentences. We evaluate our model and perform significance testing using ROUGE on the CNN/DailyMail datasets compare with six baselines, which include two traditional methods and four state-of-art deep learning model. The results validate the effectiveness of our approach, which leverages K-means algorithm to produce more accurate and less repeat sentences in semantic summaries.

Ultrasound, as an efficient, clean, and safe processing technology, is widely used in industries. Grain refiners are widely used in the refinement of cast alloys. In this study, ultrasonic technology (UT) and Al–5Ti–1B refiner prepared by continuous rheological extrusion (CRE Al–5Ti–1B) were used to modify the recycled Al–Mg–Si-based alloy, and the microstructure and mechanical properties of the recycled Al–Mg–Si-based alloy were studied. The differences in porosity and grain refinement caused by ultrasonic power were discussed. Results showed that, increasing the ultrasonic power can effectively reduce the porosity of the recycled Al–Mg–Si-based alloy. The synergistic effect of UT and CRE Al–5Ti–1B refiner significantly refined α-Al grains and second phases. The increase of ultrasonic power can effectively cause deagglomeration while reducing the nucleation undercooling of α-Al, which promotes the refinement of the recycled Al–Mg–Si-based alloy and significantly improves the mechanical properties. The yield strength (YS), ultimate tensile strength (UTS) and elongation (EL) of the recycled Al–Mg–Si-based alloy were 106 MPa, 210 MPa and 9.4%, respectively. When 0.2 wt% CRE Al–5Ti–1B refiner was added and the ultrasonic power was 150 W, the YS, UTS, and EL were improved by 12.8%, 28.8% and 228.4%, respectively.

Abstract DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Abstract Background Investigating the trend of changes in the occurrence of necrotizing enterocolitis (NEC) in preterm infants during 9 years and analyzing the risk factors of NEC with the purpose of providing reference for clinical diagnosis and treatment of NEC. Methods Clinical data of NEC in preterm infants with Bell’s stage ≥ II from January 2013 to December 2021 in the Neonatology Department of the Third Affiliated Hospital of Zunyi Medical University was retrospectively analyzed. Trends in the occurrence of NEC in preterm infants were analyzed by the trend chi-square test. Subsequently, the general data (sex, gestational age, singleton or multiple births, birth weight, serum albumin, alkaline phosphatase, sepsis, blood transfusion, mechanical ventilation, RDS, arterial catheterization) and perinatal data (intrauterine distress, turbid amniotic fluid, premature rupture of membranes, mode of delivery, fetal heart abnormalities, diabetes mellitus) were collected; then, the risk factors for NEC were analyzed by univariate and multivariate logistic-regression analysis. Results In the past 9 years, 77 cases of NEC occurred, with the incidence rate of 1.95%, and the incidence of NEC in preterm infants has been increasing year by year (P

Objective To analyze the correlation of HBV serological characteristics between non-reproducible reactivity (NRR) samples and occult hepatitis B virus infection (OBI) samples for blood screening. Methods A total of 144 samples with negative ELISA (HBV, HCV and HIV test) results and reactive nucleic acid tests(NAT) were collected from January 2021 to January 2023 in Anhui Blood Center, including 92 reactive samples by TMA method (combined ID-NAT) and 52 HBV DNA reactive samples by PCR method (ID-NAT). Supplementary differential testing and ID-NAT by PCR were performed on the reactive samples of the combined ID-NAT, samples that were non-reactive by both differential testing and ID-NAT by PCR were included in the NRR group, and samples that were reactive for HBV DNA detected by either method were included in the OBI group. Supplemented with HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc tests, the differences in serological pattern and positive rate between NRR samples and OBI samples were analyzed. Results A total of 53 samples were negative for differential testing and ID-NAT and were included in the NRR group, 91 samples were detected as HBV DNA reactive in either method and were included in the OBI group. HBsAg and HBeAg were not detected by serological testing in either group. The detection rates of anti-HBs, anti-HBc and anti-HBe in the NRR group and the OBI group were 64.15% vs 47.25%, 86.79% vs 94.51%, 35.85% vs 52.75%, respectively. Comparison of serological patterns between the two groups: the most frequent pattern in the NRR group was anti-HBs (+ ) and anti-HBc (+ ) (32.08%), and the most frequent pattern in the OBI group was anti-HBe (+ ) and anti-HBc (+ ) (37.36%). Conclusion There were differences in some of the test results between the NRR samples and the OBI samples in HBV serological testing, and higher anti-HBc positive rate in the NRR samples suggests a higher possibility of HBV infection.

Designing an active, selective, and stable catalyst for catalytic polyolefin pyrolysis is crucial for enhancing energy efficiency and economic viability in chemical processes. In this study, two synthesis methods—NaOH and NaOH/CTAB treatments—were employed to modify the physicochemical properties of CBV23, CBV55, and CBV80 zeolites. The catalytic performance of both parent and modified zeolites was evaluated for polypropylene pyrolysis using a two-stage micro-pyrolyzer coupled with two-dimensional GC-FID/MS. The NaOH/CTAB treatment preserved and enhanced strong acid sites while promoting a more uniform mesopore distribution. Among the catalysts tested, the hierarchical CBV80-ZM exhibited the best performance, achieving a propylene yield of 41 wt% and total light olefin and MA yields of 92 wt%. The improved catalytic performance was attributed to optimized acidity and larger pore size, which reduced the number of weak acid sites. These findings offer valuable insights for designing tailored zeolites based on specific target products for catalytic pyrolysis of plastic waste, particularly in the production of propylene and other high-value chemicals.

Rabies is a highly lethal infectious disease with no existing treatment available, thus investigating effective antiviral compounds to control rabies virus (RABV) infection is of utmost importance. Resveratrol is a natural phenolic compound that, as a phytoalexin, exhibits several biological activities, including antiviral activity. In this study, we evaluated the inhibitory effect of resveratrol on RABV infection and investigated its molecular antiviral mechanism. We found that resveratrol significantly inhibited RABV infection, including the phases of adsorption, replication, and release, and also directly inactivated RABV and inhibited its infectivity. However, resveratrol had no significant effect on RABV internalization. Resveratrol also reduced RABV-induced oxidative stress, specifically reactive oxygen species and malondialdehyde levels. Western blotting analysis revealed that resveratrol enhanced antioxidant signaling via the SIRT1/Nrf2/HO-1 pathway and inhibited viral replication. Viral infection was enhanced after SIRT1 knockdown, which inhibited the SIRT1/Nrf2/HO-1 antioxidant signaling pathway, suggesting that this pathway plays an important role in RABV replication. Overall, resveratrol prevented the adsorption, replication, and release of RABV and directly inactivated RABV, but failed to inhibit RABV internalization. Furthermore, resveratrol activated the SIRT1/Nrf2/HO-1 pathway to inhibit RABV replication and suppressed RABV-induced oxidative stress. These findings highlight the therapeutic potential of resveratrol for fighting RABV infections.

Path planning for multiple unmanned aerial vehicles (UAVs) is crucial in collaborative operations and is commonly regarded as a complicated, multi-objective optimization problem. However, traditional approaches have difficulty balancing convergence and diversity, as well as effectively handling constraints. In this study, a directional evolutionary non-dominated sorting dung beetle optimizer with adaptive stochastic ranking (DENSDBO-ASR) is developed to address these issues in collaborative multi-UAV path planning. Two objectives are initially formulated: the first one represents the total cost of length and altitude, while the second represents the total cost of threat and time. Additionally, an improved multi-objective dung beetle optimizer is introduced, which integrates a directional evolutionary strategy including directional mutation and crossover, thereby accelerating convergence and enhancing global search capability. Furthermore, an adaptive stochastic ranking mechanism is proposed to successfully handle different constraints by dynamically adjusting the comparison probability. The effectiveness and superiority of DENSDBO-ASR are demonstrated by the constrained problem functions (CF) test, the Wilcoxon rank sum test, and the Friedman test. Finally, three sets of simulated tests are carried out, each including different numbers of UAVs. In the most challenging scenario, DENSDBO-ASR successfully identifies feasible paths with average values of the two objective functions as low as 637.26 and 0. The comparative results demonstrate that DENSDBO-ASR outperforms the other five algorithms in terms of convergence accuracy and population diversity, making it an exceptional optimization approach to path planning challenges.

ObjectiveThe aim of this study was to evaluate the effectiveness of burosumab therapy in children with X-Linked Hypophosphatemia (XLH).Materials and methodsWe systematically reviewed literature from PubMed, Web of Science, The Cochrane Library, and Embase up until January 2024, using EndNote Web for study organization. The Newcastle–Ottawa scale guided quality assessment, while Revman software was used for data analysis and visualization. Study selection, quality evaluation, and data aggregation were independently performed by three researchers.ResultsThe meta-analysis encompassed ten studies, including eight cohort studies that examined burosumab’s impact pre- and post-administration, and two randomized controlled trials comparing burosumab to standard therapy. The evidence from this review suggests burosumab’s superiority in managing XLH in pediatric populations, particularly in improving key biochemical markers including 1,25-dihydroxyvitamin D (1,25-(OH)2D), phosphorus, and alkaline phosphatase (ALP), alongside improvements in the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), and significant skeletal improvements as indicated by the rickets severity score (RSS) and the 6-minute walk test (6MWT). However, the long-term safety and effects, including height and quality of life (QOL) data, remains to be elucidated.ConclusionsBurosumab has shown significant therapeutic effectiveness in treating children with XLH, highlighting its potential as a key treatment option.

BackgroundAcute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide. In recent years, ACS has been reported to be associated with age, and the incidence has become more common in younger patients. Previous studies have identified various risk factors that contribute to the stratification of ACS patients. However, it remains unclear whether these risk factors, along with proteomic and clinical characteristics, are applicable to young ACS patients, as they are for middle-aged and elderly patients. This study aimed to investigate the proteomics, risk factors, and clinical characteristics of young ACS patients, as well as the differences between them and middle-aged and elderly ACS patients. By comparing these findings with those of middle-aged and elderly patients, we aimed to identify any discrepancies and these findings possibly may have implications for future management strategies of this specific population.MethodsThis observational study included a total of 187 participants diagnosed with ACS and 17 young healthy individuals as the control group. ACS patients were divided into three age groups:

Abstract Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33–104.96% for the maximum plasma concentration (Cmax), 97.21–102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0–t), and 97.22–102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0–∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28–110.69% for the minimal BIS value (BISmin), 99.23–101.17% for the area under the BIS time curve from time 0–60 min after administration (BISAUC0–60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00–125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance. Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Abstract Powered by data-driven technologies, precision agriculture offers immense productivity and sustainability benefits. However, fragmentation across farmlands necessitates distributed transparent automation. We developed an edge computing framework complemented by auction mechanisms and fuzzy optimizers that connect various supply chain stages. Specifically, edge computing offers powerful capabilities that enable real-time monitoring and data-driven decision-making in smart agriculture. We propose an edge computing framework tailored to agricultural needs to ensure sustainability through a renewable solar energy supply. Although the edge computing framework manages real-time crop monitoring and data collection, market-based mechanisms, such as auctions and fuzzy optimization models, support decision-making for smooth agricultural supply chain operations. We formulated invisible auction mechanisms that hide actual bid values and regulate information flows, combined with machine learning techniques for robust predictive analytics. While rule-based fuzzy systems encode domain expertise in agricultural decision-making, adaptable training algorithms help optimize model parameters from the data. A two-phase hybrid learning approach is formulated. Fuzzy optimization models were formulated using domain expertise for three key supply chain decision problems. Auction markets discover optimal crop demand–supply balancing and pricing signals. Fuzzy systems incorporate domain knowledge into interpretable crop-advisory models. An integrated evaluation of 50 farms over five crop cycles demonstrated the high performance of the proposed edge computing-oriented auction-based fuzzy neural network model compared with benchmarks.

Abstract Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS–based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post–projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 35 external calibrants to eliminate the impact of LC setups on projection accuracy. Results showed that post–projection calibration consistently achieved a median projection error below 3.2% of the elution time. The ranking results of putative candidates reached similar levels among different CMs. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.

Abstract Background The diameter of the ostial and proximal left main coronary artery can be greater than 5.0 mm. However, the diameters of the mostly available coronary drug-eluting stents (DESs) are ≤ 4.0 mm. Whether high-pressure dilatation can increase the diameter of stents from 4.0 to 5.0 mm and whether post-dilatation leads to longitudinal stent deformation (LSD) of 4.0-mm-diameter stents have rarely been studied. Therefore, this study aims to evaluate LSD and stent malapposition of six types of commercially available 4.0-mm-diameter stents in China in a 5.0-mm-diameter artificial blood vessel model by optical coherence tomography (OCT) in vitro. Methods The left main coronary artery was simulated by a truncated cone-shaped silicone tube. The internal diameters were 4.0 mm at one end of the silicone tube and 5.0 mm at the other end. Six different types of coronary stents widely used in China were selected for this study. Each stent was respectively implanted into the simulated blood vessel and dilated to a diameter of 4.2 mm according to the stent-balloon pressure compliance table. The stents were subjected to post-dilatation with a 5.0 × 15-mm noncompliant balloon. The LSD ratio of the longitudinal axis of each stent and stent malapposition were measured through OCT, and any fractures of the stents were determined. Results None of the six types of stents fractured following post-dilatation. The longitudinal axes of the BuMA and Excrossal stents were slightly shortened, while the other stents were elongated after high-pressure post-dilatation. All stents expanded to a diameter of 5.0 mm without incomplete stent apposition, except for the Nano Plus stent, which remained malapposed after high-pressure post-dilatation. Conclusion All 4.0-mm-diameter stents can be expanded to a diameter of 5.0 mm by noncompliant balloon post-dilatation without stent strut fracture. Most stents were found to be well apposed after high-pressure post-dilatation. However, LSD was observed after post-balloon dilatation. Stent malapposition might be positively correlated with the percentage change in stent length.

Abstract Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted ‘reduction, replacement and refinement’ principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.

Abstract Type 2 diabetes with hyperuricaemia may lead to gout, kidney damage, hypertension, coronary heart disease, etc., further aggravating the condition of diabetes as well as adding to the medical and financial burden. To construct a risk model for hyperuricaemia in patients with type 2 diabetes mellitus based on artificial neural network, and to evaluate the effectiveness of the risk model to provide directions for the prevention and control of the disease in this population. From June to December 2022, 8243 patients with type 2 diabetes were recruited from six community service centers for questionnaire and physical examination. Secondly, the collected data were used to select suitable variables and based on the comparison results, logistic regression was used to screen the variable characteristics. Finally, three risk models for evaluating the risk of hyperuricaemia in type 2 diabetes mellitus were developed using an artificial neural network algorithm and evaluated for performance. A total of eleven factors affecting the development of hyperuricaemia in patients with type 2 diabetes mellitus in this study, including gender, waist circumference, diabetes medication use, diastolic blood pressure, γ-glutamyl transferase, blood urea nitrogen, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose and estimated glomerular filtration rate. Among the generated models, baseline & biochemical risk model had the best performance with cutoff, area under the curve, accuracy, recall, specificity, positive likelihood ratio, negative likelihood ratio, precision, negative predictive value, KAPPA and F1-score were 0.488, 0.744, 0.689, 0.625, 0.749, 2.489, 0.501, 0.697, 0.684, 0.375 and 0.659. In addition, its Brier score was 0.169 and the calibration curve also showed good agreement between fitting and observation. The constructed artificial neural network model has better efficacy and facilitates the reduction of the harm caused by type 2 diabetes mellitus combined with hyperuricaemia.

In recent years, detecting anomalies in networks has attracted much attention in the literature. Researchers have developed various statistical process control (SPC) techniques to monitor the communication level within the networks. It is quite common to see the nodes belonging to some densely connected communities or subgroups and the nodes within a community communicate with each other more frequently than with nodes from other communities. However, we can find scarce SPC techniques that consider the multiple community labels and heterogeneity of nodes simultaneously. It is necessary to overcome this drawback to improve the change detection efficiency. This article establishes a new mixed-membership stochastic block model to characterize the multiple community labels and heterogeneity of nodes simultaneously. Then a new control chart is developed based on generalized likelihood ratio test (GLRT). The proposed control chart can be easily implemented in practice and avoids constant parameter estimation in Phase II monitoring. Numerous simulation studies and a real example show the advantages of proposed chart over existing ones.

In recent decades, grain refiners had not only improved the properties on cast aluminum alloy, but also changed the application field of cast aluminum alloys, which had attracted widespread attention. However, there were few reports on microstructure evolution of A356/CRE Al-X-Ce(Ti, C) system by combining traditional grain refiners with element Ce. In this study, refined A356 alloys with excellent strength and plasticity were obtained by adding CRE Al-X-Ce(Ti, C) (0, 0.4, 0.8, 1.2, 1.6 and 2.0 wt%, respectively). Using XRD, SEM and TEM, the morphology of phases in the refined A356 alloy and phases of grain refiner were identified. The microstructure evolution of α-Al grains and eutectic Si with the introduction of TiC and Ce was analyzed. The results showed that the novel CRE Al-X-Ce(Ti, C) could not only effectively refine α-Al grains, but also modify Si microstructure of the alloy. The refined A356 alloys with excellent strength and plasticity were obtained with 2.0 and 1.6 wt% grain refiner (CRE) additions, respectively. TiC as nucleation particle and Ce as the surfactant refined the α-Al grains. Also, Ce modified eutectic Si by changing the way it grows. When the CRE Al-X-Ce(Ti, C) content researched 2.0 wt%, the long plate-like Al–Si–Ce phase was formed which can easily caused cracks and reduced the elongation of alloy.

Background This research investigates the metabolic profiles of follicular fluid (FF) samples from patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilisation and aims to identify diagnostic and therapeutic biomarkers for PCOS through lipidomic analysis.Methods We performed non-targeted lipid analysis of FF samples from women with PCOS (n = 6) and normal controls (n = 6) using ultra-high-performance liquid chromatography–tandem mass spectrometry. Differential lipids between the two groups were screened using multidimensional statistical analysis, followed by fold change analysis and t-tests to identify potential PCOS biomarkers.Results Multivariate statistical analysis revealed significant differences in FF lipid levels between the PCOS and control groups. Five different lipids were selected as standards, with p

ABSTRACTEnhancing health professional students’ effective learning and collaborative practice requires a deep understanding of strategies for facilitating interprofessional learning. While faculty members and clinical preceptors are recognized as facilitators in interprofessional education (IPE), there is limited knowledge about the impact of student facilitators’ engagement in IPE. Accordingly, this study aims to explore the perceptions and experiences of student facilitators in IPE. Thirteen student facilitators were recruited to lead an interprofessional learning program, and they were subsequently invited to participate in one-on-one interviews. An interview guide was developed to explore their motivations, expectations, engagement, effectiveness, and achievements in IPE facilitation. Thematic analysis was conducted using MAXQDA software to analyze the student facilitators’ experiences and perceptions. Eight interviewees from various disciplines, including Medicine, Nursing, Pharmacy, Speech and Hearing Sciences, and Social Work, took part in the study. The findings revealed that student facilitators highly valued their IPE facilitation experience, which aligned with their expectations and led to the creation of social networks, increased confidence, improved understanding of other professions, and the development of lifelong skills. Furthermore, the student facilitators demonstrated cognitive and social congruence by establishing a relaxed learning environment, displaying empathetic and supportive behaviors, and using inclusive language to engage IPE learners in group discussions. This study provides a comprehensive understanding of the role of student facilitators in IPE, contributing to the evolving literature on IPE. A conceptual framework was developed to explore the entire facilitation experience, encompassing the motivations and expectations of student facilitators, their engagement and effectiveness, and the observed achievements. These findings can inform the development of peer teaching training in IPE and stimulate further research in identifying relevant facilitator competencies for optimal delivery of IPE.

Abstract Soil moisture (SM) plays an important role in regulating regional weather and climate. However, the simulations of SM in current land surface models (LSMs) contain large biases and model spreads. One primary reason contributing to such model biases could be the misrepresentation of soil texture in LSMs, since current available large‐scale soil texture data are often generated from extrapolation algorithm based on a scarce number of in‐situ geological measurements. Fortunately, recent advancements in satellite technology provide a unique opportunity to constrain the soil texture data sets by introducing observed information at large spatial scales. Here, two major soil texture baseline data sets (Global Soil Data sets for Earth system science, GSDE and Harmonized World Soil Data from Food and Agriculture Organization, HWSD) are optimized with satellite‐estimated soil hydraulic parameters. The optimized soil maps show increased (decreased) sand (clay) content over arid regions. The soil organic carbon (SOC) content increases globally especially over regions with dense vegetation cover. The optimized soil texture data sets are then used to run simulations in one example LSM, that is, Noah LSM with Multiple Parameters. Results show that the simulated SM with satellite‐optimized soil texture maps is improved at both grid and in‐situ scales. Intercase comparison analyses show the SM improvement differs between simulations using different soil maps and soil hydraulic schemes. Our results highlight the importance of incorporating observation‐oriented calibration on soil texture in current LSMs. This study also joins the call for a better soil profile representation in the next generation of Earth System Models (ESMs).

Carotid atherosclerosis-related stenosis, marked by atherosclerotic plaque formation in the carotid artery, significantly increases ischemic stroke risk. Its prevalence varies across ethnic groups, reflecting racial disparities. Epidemiological studies have highlighted different susceptibilities to carotid stenosis among racial groups. Native Americans and Whites show greater vulnerability, indicating genetic and environmental influences. The impact of carotid stenosis is more severe in Hispanic and Black populations, with a higher incidence of related brain injuries, underscoring the need for targeted interventions. Comparative imaging studies between Chinese and White individuals reveal unique patterns of carotid stenosis, enhancing understanding of its pathophysiology and management across ethnicities. This review also categorizes risk factors, distinguishing those with racial disparity (such as genetic loci, sleep apnea, and emotional factors, socioeconomic status) from those without. In summary, racial disparities affect carotid stenosis, leading to varying susceptibilities and outcomes among ethnic groups. Recognizing these differences is essential for developing effective prevention, diagnosis, and management strategies. Addressing these disparities is critical to reducing ischemic stroke’s burden across populations. Continued research and targeted interventions are crucial to improve outcomes for individuals at risk of carotid stenosis and its complications.

Emerging viruses, such as filoviruses (Ebola, Marburg), SARS and MERS coronaviruses, and Zika, pose significant threats to global public health, particularly for individuals with co-morbidities. To address these challenges, this review article explores multidisciplinary strategies for combatting emerging viruses. We emphasize the importance of developing accurate diagnostics, innovative therapeutic gene and vaccine delivery systems, and long-acting nanotherapeutics. These approaches are designed to enhance the safety and efficacy of treatments against these deadly pathogens. We discuss the collaborative efforts of virologists, geneticists, formulation scientists, clinicians, immunologists, and medicinal chemists in advancing these therapeutic modalities.

Abstract The immunological implications of cuproptosis, a form of cell death highly sensitive to oxygen presence, remain largely unexplored in the context of tumor immunotherapy. Herein, we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis. Subsequently, an oxygen generator loaded with copper ions (Cu/APH‐M) has been constructed, which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment. Importantly, Cu/APH‐M‐mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA‐sequencing analysis, but also effectively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy, creating a robust immune memory effect. Our work reveals the beneficial effects of enhanced cuproptosis in radio‐immunotherapy and elucidates its underlying mechanisms, which provides a novel approach for the synergistic integration of cuproptosis with immunotherapy and radiotherapy, broadening the scope of cuproptosis‐mediated tumor therapy.

Debris flow is a common geological disaster in mountainous areas, which occurs frequently in the rainy season and has strong mobility and destructiveness, often bringing serious loss of life and property. Previous studies have focused more on single outbreaks of debris flow disasters, and less on multiple outbreaks of debris flow disasters in the same gully during the rainy season, which makes it more difficult to carry out prevention and control work for similar disasters. Because the occurrence of the disaster has its corresponding geomechanical model as the basis, which provides the necessary scientific basis for the prevention and control of the disaster. Through data collection, field investigation, drone aerial photography, modelling and rainfall data analysis, the geological environment of Yizhong River Basin and the frequent occurrence mechanism of debris flow disasters were investigated, and a conjugate shear-type disaster-inducing geomechanical model was proposed. With the help of RAMMS numerical simulation software, the dynamic mechanism of the disaster threatening the life and property safety of the residents in Deqin County was analysed to provide the necessary scientific basis for the prevention and control of the Yizhong River debris flow disaster. Base on the characteristics of the geological environment in alpine and gorge areas, the necessity and advantage of applying the nap-of-the-object photogrammetry technology to engineering geological survey in alpine and gorge areas are put forward.

One of the critical technologies to ensure cyberspace security is network traffic anomaly detection, which detects malicious attacks by analyzing and identifying network traffic behavior. The rapid development of the network has led to explosive growth in network traffic, which seriously impacts the user's information security. Researchers have delved into intrusion detection as an active defense technology to address this challenge. However, traditional machine learning methods struggle to capture complex threats and attack patterns when dealing with large-scale network data. In contrast, deep learning methods have the advantages of automatically extracting features from network traffic data and strong generalization capabilities. Aiming to enhance the ability of network anomaly traffic detection, this paper proposes a network traffic anomaly detection based on Deep Residual Shrinkage Network (DRSN), namely ''GSOOA-1DDRSN''. This method uses an improved Osprey optimization algorithm to select the most relevant and essential features in network traffic, reducing the features' dimensionality. For better detection performance of network traffic anomalies, a one-dimensional deep residual shrinkage network (1DDRSN) is designed as a classifier. Validation is performed using the NSL-KDD and UNSW-NB15 datasets and compared with other methods. The experimental results show that GSOOA-1DDRSN has improved multi-classification accuracy, precision, recall, and F1 Score by approximately 2 % and 3 %, respectively, compared to the 1DDRSN model on two datasets. Additionally, it reduces the time computation costs by 20 % and 30 % on these datasets. Furthermore, compared to other models, GSOOA-1DDRSN offers superior classification accuracy and effectively reduces the number of features.

Land Surface Temperature (LST) is important for diagnosing surface energy balance in land surface models (LSMs). However, LST simulation in current LSMs tends to show large cold biases, partially due to the reason that the model's prescribed vegetation parameters (e.g., Leaf Area Index (LAI) and Fraction of Vegetation Cover (FVC)) are misrepresented, especially in regions with complex topography and climate such as Tibetan Plateau. Recent advancements in remote sensing technologies provide a unique opportunity to improve the model's vegetation parameters at large scales. In this study, we practice two experiments to improve LST simulations in Noah-MP LSM by (1) incorporating LAI and FVC from the Global Land Surface Satellite (GLASS) remote sensing product (exp_RS); and (2) incorporating an empirical LAI and FVC parameterization scheme based on the soil temperature stress factor (exp_RL02). Results show that the effect of vegetation on simulated LST is the most significant in summer season when the model-satellite LAI and FVC differences are the largest. Compared to the default experiment that uses static LAI and FVC values from the model's look-up table (exp_CTL), the results in exp_RS and exp_RL02 show domain-wide improvement of the simulated LST. The LAI and FVC effect on LST are also well reflected in model's energy budget components (i.e., longwave emissivity, sensible and latent heat fluxes, etc). Validation of the model simulated soil temperature with in-situ observations further demonstrate the model improvements. Our study underscores the important role of vegetation in regulating surface energy transfer processes. Our study also highlights the feasibility and benefit of incorporating remote sensing data in improving land surface model simulations.

Objective Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment.Methods This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference.Results We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR 38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR

Abstract Deserts play an important role in the climate system, which is closely associated with the emission and transport of dust aerosols. Based on the intensive observation experiment in the Taklimakan Desert, the potential physical processes between the deep convective boundary layer (CBL) and dust emission are revealed in this study. Deep CBL enables the formation of clouds in the late afternoon, leading to significant cooling of surface. Large‐scale buoyant coherent structures thereby transform into the mechanical coherent structures confined near the surface. The responses promote the earlier occurrence of low‐level jet (LLJ) than in cloudless conditions, which allows the downward transport of LLJ momentum and substantially increases surface wind. Therefore, dust emission is initiated by strong wind at dusk and lasts for several hours. The results are useful to predict dust emissions and improve our understanding of distinctive boundary‐layer processes in desert regions.

Abstract This study aims to investigate the mechanism of platelet activation‐induced thrombosis in patients with acute non‐ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy‐associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un‐offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy‐associated proteins and the expression of autophagy‐associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un‐offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy‐related protein expression decreased, and the expression of αIIbβ3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbβ3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI.

Abstract Vibrio is a salt‐tolerant heterotrophic bacterium that occupies an important ecological niche in marine environments. However, little is known about the contribution of resource diversity to the marine Vibrio diversity and community stability. In this study, we investigated the association among resource diversity, taxonomic diversity, phylogenetic diversity, and community stability of marine Vibrio in the Beibu Gulf. V. campbellii and V. hangzhouensis were the dominant groups in seawater and sediments, respectively, in the Beibu Gulf. Higher alpha diversity was observed in the sediments than in the seawater. Marine Vibrio community assembly was dominated by deterministic processes. Pearson's correlation analysis showed that nitrite (NO2−‐N), dissolved inorganic nitrogen (DIN), ammonium (NH4+‐N), and pH were the main factors affecting marine Vibrio community stability in the surface, middle, and bottom layers of seawater and sediment, respectively. Partial least‐squares path models (PLS‐PM) demonstrated that resource diversity, water properties, nutrients, and geographical distance had important impacts on phylogenetic and taxonomic diversity. Regression analysis revealed that the impact of resource diversity on marine Vibrio diversity and community stability varied across different habitats, but loss of Vibrio diversity increases community stability. Overall, this study provided insights into the mechanisms underlying the maintenance of Vibrio diversity and community stability in marine environments.

BackgroundDiabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined.MethodsBased on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy.ResultsA substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell.ConclusionsOur findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice.

Introduction:Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism’s pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets.Methods:Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed.Results:MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol’s binding to IRF3, indicating a stable interaction.Conclusion:This study comprehensively elucidates inflammation, immune response, and metabolism’s intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo’s etiology, informing future research and drug development endeavors.

Morphological changes in estuaries are typically discussed on decadal time scales, with reported changes often exceed several decimeters. In our study, we utilized refined in-situ data to investigate bed-level changes and rapid accretion-erosion transitions during tidal cycles off the Changjiang Estuary. A field study employing a high-resolution bottom tripod system was conducted, measuring various parameters such as water level, waves, velocity profiles, near-bottom suspended sediment concentration (SSC), and bed level changes over ten tidal cycles. Our findings reveal significant and intense bed level changes occurring at the scale of tidal cycles. The data suggests that downward sediment transport plays a dominant role in the overall accretion tendency throughout the study period. Additionally, our research introduces a dynamic critical bed shear stress that increases during tidal cycles, deviating from fixed values. We also present a new quadrant analysis method to elucidate the primary processes controlling near-bed sediment transport. The results highlight the importance of horizontal advective sediment transport in frequent accretion-erosion transitions at tidal-cycle timescales. This implies a frequent exchange of sediment between adjacent shoals and channels in the seaward region of the North Channel in the Changjiang Estuary, which holds significance for future navigation and construction management.

We aimed to investigate the improvement effect of Beclin-1 on the cognitive function of mice with Alzheimer"s disease (AD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were isolated from neonatal umbilical cord tissues. The cells stably overexpressing Beclin-1 were constructed, and those of passages 5, 10, and 15 were used. Forty-eight AD mice were randomly divided into AD, P5 hUC-MSCs, P15 hUC-MSCs (P15MSCs) and OE Beclin 1-P15 hUC-MSCs (OE Bec-P15MSCs) groups (n=12). Overexpressing Beclin-1 significantly enhanced the proliferation and migration of MSCs of different passages, and reduced G0/G1 arrest. The OE Bec-P15MSCs group had the longest total distance, the shortest time in forced swimming test, and the largest total food consumption in novelty suppressed feeding test. Transplanting hUC-MSCs and overexpressing Beclin-1 significantly reduced Aβ deposition. The expressions of P-tau (Ser396), P-tau (Ser231) and P-tau (Ser235) were significantly inhibited by hUC-MSCs transplantation and Beclin-1 overexpression, especially in the OE Bec- P15MSCs group. Double positive staining of EdU+/DCX+ cells, EdU+/NeuN+ cells and EdU+/Nestin+ cells significantly increased in the OE Bec-P15MSCs group compared to those in other groups (P

Nanchuan area in southeastern Chongqing is rich in normal pressure shale gas resources, which is an important area for SINOPEC's shale gas exploration and development. Due to the complex geological conditions and imperfect engineering technology, the overall efficiency of drilling acceleration and efficiency improvement in this area can not meet the requirements for large-scale benefit-based development of normal pressure shale gas. Therefore, Yangye 54-3HF well in Yangchungou block in this area is selected as the first normal pressure shale gas demonstration well of SINOPEC to research and form a regional optimal and fast drilling and completion demonstration technology series. On the basis of systematic analysis of regional drilling technology difficulties, combined with basic research on formation pressure resistance characteristics and formation pressure system, the demonstration well research systematically explores key drilling technologies such as shallow formation leakage technology, well structure optimization technology, accelerating tool optimization technology, trajectory control and orientation technology, low-density strong plugging oil-based drilling fluid technology, and optimal fast completion technology. A low-cost, optimal, and fast drilling demonstration technology system with the core of shallow formation prospecting, large-capacity clean water drilling, optimized well structure, domestic acceleration tools, low-density and strong plugging oil-based drilling fluid, integrated geological engineering orientation, and low-pressure wellbore fast cementing technology is formed. The drilling period of the demonstration well is 19.96 d, which is the shortest drilling period in 4 500 m well depth in China, and the ROP is 24.88 m/h, which is 141.79% higher than the fastest ROP of 10.29 m/h in the similar well depth in the same region. The rate of drilling in high-quality shale is 100%, and the cementing quality is excellent, which has played a good demonstration and leading role. After the promotion and application, various technical and economic indicators such as the regional ROP and drilling period have been significantly improved, speeding up the exploration and development process of normal pressure shale gas in Nanchuan area. The practice of normal pressure shale gas demonstration wells in Nanchuan area has shown that the efficient drilling and completion technology series formed by the demonstration well research can meet the requirements of drilling acceleration and efficiency improvement in horizontal wells of normal pressure shale gas, effectively promoting the four improvements in petroleum engineering to a new level, and laying a technical foundation for the construction of similar gas fields around the Sichuan Basin, and helping achieve greater progress in stabilizing oil and gas production, reducing costs, and improving efficiency in the upstream industry in China.

In recent years, land subsidence issues have become relatively prominent in the northern plain area of Anhui province, and there is lack of quantitative research on the driving forces of regional land subsidence. In order to further investigate the developmental characteristics of subsidence disasters and provide scientific, this paper takes Bozhou City as an example. Based on 62 scenes of Sentinel-1 data, SBAS-InSAR technology is employed to obtain the spatial-temporal distribution characteristics of land subsidence from October 2021 to October 2022. Additionally, a geographic weighted regression model is applied to explore the main driving factors of land subsidence in Bozhou city. The research results indicate: (1) The main subsidence rate in Bozhou City ranges from 5 to 30 mm/year,with an average subsidence rate of 5.7 mm /year. (2) The most serious subsidence area is located north of Gongji Temple Town in Woyang County, with an amplitude of 84.3 mm/year, mainly caused by coal mining. In non-coal mining subsidence areas, the maximum subsidence rate is 25.8 mm/year, located in the northeast of Qiaocheng District. (3) The contribution order of various driving factors to ground subsidence is as follows: fluctuation of deep water level, fluctuation of middle-deep water level, burial depth of middle-deep groundwater, burial depth of deep groundwater, GDP per unit area, thickness of loose layer, road density, and population density. The study results can provide basic data support for geological disaster prevention and control.

Yaks are important food animals in China; however, bacterial diarrheal diseases frequently occur on the plateau, with limited effective therapies. The objective of this research was to evaluate the effectiveness of Lactobacillus salivarius (LS) and berberine in alleviating diarrhea in yak calves. For this purpose, eighteen healthy yak calves were divided into control (JC), infected (JM), and treatment (JT) groups. Yaks in the JT group were treated with 2 × 1010 CFU/calf L. salivarius and 20 mg/kg berberine, and yaks in the JM and JT groups were induced with multi-drug-resistant Escherichia coli. The results showed that the weight growth rate in the JM group was significantly lower than that in the JC and JT groups. The diarrhea score in the JM group was significantly higher than that in both the JC and JT groups. Additionally, the contents of T-AOC, SOD, GSH-Px, and IL-10 were significantly lower in the JM group than those in the JC and JT groups, while MDA, TNF-α, IL-1β, and IL-6 were significantly higher in the JM group. Microbiota sequencing identified two phyla and twenty-seven genera as significant among the yak groups. Notably, probiotic genera such as Faecalibaculum and Parvibacter were observed, alongside harmful genera, including Marvinbryantia and Lachnospiraceae UCG-001. Our findings indicate that treatment with L. salivarius and berberine significantly reduced diarrhea incidence, improved growth performance, and positively modulated intestinal microbiota, which could provide novel insights for developing new therapies for ruminant diarrhea.

The long-term atmospheric mixing layer height (MLH) information plays an important role in air quality and weather forecasting. However, it is not sufficient to study the characteristics of MLH using long-term high spatial and temporal resolution data in the desert. In this paper, over the southern edge of the Taklimakan Desert, the diurnal, monthly, and seasonal variations in the daytime MLH (retrieved by coherent Doppler wind lidar) and surface meteorological elements (provided by the local meteorological station) in a two-year period (from July 2021 to July 2023) were statistically analyzed, and the relationship between the two kinds of data was summarized. It was found that the diurnal average MLH exhibits a unimodal distribution, and the decrease rate in the MLH in the afternoon is much higher than the increase rate before noon. From the seasonal and monthly perspective, the most frequent deep mixing layer (>4 km) was formed in June, and the MLH is the highest in spring and summer. Finally, in terms of their mutual relationship, it was observed that the east-pathway wind has a greater impact on the formation of the deep mixing layer than the west-pathway wind; the dust weather with visibility of 1–10 km contributes significantly to the formation of the mixing layer; the temperature and relative humidity also exhibit a clear trend of a concentrated distribution at about the height of 3 km. The statistical analysis of the MLH deepens the understanding of the characteristics of dust pollution in this area, which is of great significance for the treatment of local dust pollution.