Coagulation factor XIa (FXIa) plays a crucial role in thrombus formation; therefore, the development of potent and safe FXIa inhibitors is of great significance. In this study, compound F22, previously discovered by our group, was selected as the lead compound. Based on the principles of bioisosterism and fragment-based drug design, four series comprising 14 novel Asundexian derivatives not previously reported in the literature were designed and synthesized. The structures of the target compounds were confirmed by 1H NMR and HRMS, and their inhibitory activities against FXIa were evaluated using chromogenic substrate assay. Results showed that compound FD-1 exhibited the most potent activity, with an IC50 value of 2.8 nmol/L, which was superior to that of the lead compound F22 (IC50 = 4.5 nmol/L) and the reference drug Asundexian (IC50 = 5.0 nmol/L). Furthermore, in the activated partial thromboplastin time (aPTT) assay, compound FD-1 demonstrated excellent anticoagulant activity, outperforming Asundexian, showing no significant effect on prothrombin time (PT). These findings provide valuable insights for further structural optimization and rational design of small-molecule FXIa inhibitors.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

BACKGROUND: Serum osmolality is a prognostic indicator in critically ill patients. This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest (CA) admitted to the intensive care unit (ICU). METHODS: Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV. Patients were divided into survivor and non-survivor groups according to the 28-day prognosis. Serum concentrations of sodium, potassium, glucose, and urea nitrogen on the first day of ICU admission were used to determine serum osmolarity. The primary endpoint of this study was 28-day all-cause mortality. Propensity score matching (PSM) analysis was performed to reduce bias between the survivor and non-survivor groups. RESULTS: Among the 798 included CA patients, the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality (62.0% vs. 35.5%, P<0.001) and reduced cumulative survival (log-rank P<0.05) after PSM. Cox regression identified the high osmolarity on the first day of ICU admission as an independent predictor. High serum osmolarity on the first day of ICU admission effectively predicted 1-, 3-, 7-, and 28-day all-cause mortality, with the strongest predictive performance for 1-day mortality both before and after PSM (all P<0.05). CONCLUSION: In this study, elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.

The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Objective:To characterize the etiological and genetic features of pediatric influenza outbreaks in Changzhou between 2021 and 2024，with the goal of informing evidence-based prevention strategies and guiding effective management of influenza outbreaks in school settings.Methods:During the period of 2021 to 2024，throat swabs of influenza-like cases from school outbreaks in Changzhou were collected. These samples underwent real-time reverse transcription-polymerase chain reaction（RT-PCR）testing and virus isolation. Epidemiological data were integrated to conduct pathogenetic analysis. The HA genes of isolated strains were amplified and sequenced to perform genetic characterization.Results:Between 2021 and 2024，a total of 256 influenza outbreaks were reported in schools in Changzhou. A total of 3 201 specimens were collected，of which 2 245 were tested positive for influenza viruses，resulting in a positivity rate of 70.13%. The outbreak season was primarily concentrated from December to February each year，with settings predominantly distributed in primary schools（accounting for 73.83%）. The predominant epidemic strains were influenza A viruses，including 118 outbreaks caused by H1N1 and 104 by H3N2. A total of 74 influenza virus strains were successfully isolated from positive specimens，and sequencing of the hemagglutinin（HA）gene was completed. Phylogenetic analysis revealed that certain B/Victoria lineage strains（e.g.，B/Changzhou/01/2021）clustered closely with the vaccine strain B/Austria/3594/17（bootstrap support：99%）. Among influenza H1N1 strains，multiple isolates from 2023—2024 clustered within the same major branch as A/Victoria/4897/2022（bootstrap support：100%）. In contrast，the H3N2 strains exhibited a complex evolutionary pattern，showing variable genetic distances to vaccine strains from different years（e.g.，A/Massachusetts/18/2022，A/Darwin/6/2021）；some isolates were closely related to vaccine strains，while others were more distantly related and scattered across the phylogenetic tree.Conclusions:The influenza outbreak situation in schools was severe and has significant public health implications. Continuous surveillance is essential，and preventive strategies should be promptly adjusted based on the epidemiological and genetic characteristics of circulating strains.

Exposure to acceleration can have Various effects on the physiology,psychology,and performance of human.With the increasing density and complexity of China's space mission,and the significant differences between deep space exploration and near Earth orbit flight,unprecedented challenges have been posed to the emotions of astronauts and the ability of human-machine collaboration to complete complex operational tasks in special environments.Similarly,with the continuous development of high-performance fighter jets,air combat operation are becoming increasingly complex,and the payload generated by the aircraft is also increasing.The requirements for the anti-overload ability of fighter pilots are also becoming higher and higher.A review of recent studies on physiological and cognitive load of acceleration exposure on humans.The research on human physiology is relatively systematic,but there is limited research on cognitive load.The corresponding evaluation methods,assessment methods,and assessment systems are not comprehensive enough,and there is a lack of mechanistic analysis.Multimodal analysis and modeling are even rarer.Further in-depth research is needed on the cognitive load and evaluation techniques of overweight environment in the future.This article provides reference for the selection,adaptive training,and related experimental research of overweight endurance for astronauts and pilots in the future.

ObjectiveTo explore psychological experiences and care needs of elderly patients with chronic obstructive pulmonary disease (COPD) following dysphagia. MethodsFrom April to June, 2024, 13 elderly patients with COPD and dysphagia received treatment in Yixing No. 2 People's Hospital (Yixing Occupational Disease Institute) and Northern Jiangsu People's Hospital were interviewed. Nvivo 11.0 and content analysis were employed to analyze and summarize themes. ResultsTwo main themes were identified. The psychological experiences included fear of eating due to swallowing and choking, swallowing anxiety in social situations, concerns about malnutrition, and emotional loss related to family. The care needs included improvement in swallowing function, adjustment of food texture, assistance with disease adaptation and effective access to health education information. ConclusionHealthcare professionals should thoroughly understand the psychological and needs of elderly patients with COPD-related dysphagia, and comprehensive nursing strategies should be developed and implemented to improve swallowing function and overall quality of life.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Aim To investigate the promotive effects and mechanisms of the combined use of brucine(Bru)and lumbrokinase(LK),active ingredient derived from Longma formula,in promoting chondrocyte proliferation via the Wnt/β-catenin signaling pathway.Methods The extracted primary rat chondrocytes were divided in-to the following groups:Control group,Bru,LK alone group,and Bro+LK combination group.The optimal drug concentration and intervention time were deter-mined using CCK-8 assay,followed by cell proliferation validation through EdU and phalloidin staining.The expression levels of collagen Ⅱ,aggrecan and SRY-re-lated high-mobility group box gene 9(SOX9)in chon-drocytes following intervention with the combination of Bru and LK were detected by Western blotting.Addi-tionally,the regulatory effects of these proteins on the Wnt/β-catenin signaling pathway were also investiga-ted.Results The optimal combination concentration of Longma formula active ingredients(Bru 0.025 mg·L-1+LK 5 mg·L-1)significantly enhanced chondro-cyte viability compared to control,Bru,or LK alone at 48 h.This combination increased the S-phase ratio,promoted the aggregation of intracellular actin fila-ments,and upregulated the expression of collagen Ⅱ and aggrecan.Furthermore,it activated the Wnt/β-catenin pathway,leading to increased SOX9 expres-sion.Conclusions The optimal combination of Bru and LK(Bru 0.025 mg·L-1+LK 5 mg·L-1)de-rived from Longma formula significantly maintains chondrocyte phenotype and promotes cellular prolifera-tion through the activation of the Wnt/β-catenin signa-ling pathway,which subsequently upregulates the downstream target SOX9.