AIM To investigate the effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells.METHODS In the establishment of cell model of Alzheimer's disease(AD)using Aβ25-35 on the BV-2 cells,the optimal concentration and time point of Aβ25-35 intervention were determined;and the groups for the intervention of LFHP-1c group(inhibitor)or the serum containing Wenfei Jiangzhuo Formula were set up.The detection of the optimal intervention concentration and time point by CCK-8 assay;the observation of cell migration and apoptosis by Transwell assay and Hoechst 33342 staining;the detection of the positive expressions of PGAM5 and Drp1 by immunofluorescence;and the detection of cellular PGAM5,Drp1,OPA1,and Mfn1/2 mRNA and protein expressions by RT-qPCR and Western blot were conducted.RESULTS The best AD cell model was established by 48 h exposure to 5 μmol/L of Aβ25-35,and most active cell viability was achieved with the 48 h use of serum containing 20％Wenfei Jiangzhuo Formula.Compared with the control group,the model group displayed decreased number of cell migration,more bright blue positive apoptotic cells,increased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and decreased mRNA and protein expressions of OPA1 and Mfn1/2(P＜0.05).Compared with the model group,the groups intervened with the medicines shared increased number of cell migration,less bright blue positive apoptotic cells,decreased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and elevated OPA1 and Mfn1/2 mRNA and protein expressions(P＜0.05).CONCLUSION Wenfei Jiangzhuo Formula exerts cerebroprotective effects to improve cognition by reducing cell damage and improving the balance of mitochondrial homeostasis through PGAM5-Drp1 axis in AD model.

As a cheap and effective antibiotic,sulfonamides are often used in animal husbandry.However,their residues in animal-derived foodstuffs will threaten human health.Consequently,a high-performance liquid chromatography(HPLC)method integrated with supramolecular solvent microextraction was successfully established for simultaneous quantification of sulfonamide residues sulfachlorpyridazine,sulfamethoxazole,sulfamethoxypyridazine and sulfadimethoxine in milk matrices.This approach exhibited prominent characteristics of operational simplicity,environmental sustainability,and high extraction efficiency.The supramolecular solvents prepared by tributyl octylphosphine tetrafluoroborate and tetrahydrofuran were employed as extraction solvents.The analytes underwent isolation and concentration via dispersive liquid-liquid microextraction(DLLME)prior to quantitative determination using high-performance liquid chromatography(HPLC).The composition and microscopic morphology of the supramolecular solvent were characterized through a series of analytical techniques,including phase diagram,Fourier transform infrared spectroscopy,scanning electron microscopy,and inverted fluorescence microscopy and so on.The density and pH value of supramolecular solvents were determined.The extraction conditions were optimized through the one-factor experiments.The experimental results demonstrated that under the optimal extraction conditions,the four kinds of sulfonamide antibiotics exhibited excellent linearity within respective detection range(R2 ≥ 0.9998)and the limits of detection(LOD)were 0.67-1.45 μg/L.Compared with literature methods,this approach offered some advantages such as simplicity of operation and less reagent consumption,and could be used for analysis and detection of sulfonamide antibiotic residues in milk samples.The present method provided technical support for food safety regulation and paved a new way for the application of supramolecular solvents in the field of extraction and separation.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index(DFI),we aim to identify miRNA that may impact sperm DNA integrity and target genes,and attempt to analyze their potential mechanisms of action.Methods:A total of 161 study subjects were collected and divided into normal con-trol group,DFI-medium group and DFI-abnormal group based on the DFI detection values.Differential miRNA were identified through miRNA chip analysis.Through bioinformatics analysis and target gene prediction,miRNA related to DFI and specific target genes were identified.The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI.Results:Through miRNA chip analysis,a total of 11 differential miRNA were detected.Bioin-formatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity.And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p.Compared to the normal control group,the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease,while the relative expression levels of PTEN showed an in-crease.The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values,while the relative expres-sion levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group.The AUC of miR-26a-5p in the DFI-medium group was 0.740(P＜0.05),with a sensitivity of 73.6％and a specificity of 71.5％;the AUC of PTEN was 0.797(P＜0.05),with a sensitivity of 76.5％and a specificity of 78.4％.In the DFI-abnormal group,the AUC of miR-26a-5p was 0.848(P＜0.05),with a sensitivity of 81.3％and a specificity of 78.1％.While the AUC of PTEN was 0.763(P＜0.05),with a sensitivity of 77.2％and a specificity of 80.2％.Conclusion:miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively.The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diag-nostic value for sperm DNA integrity damage,which can help in the etiological diagnosis and prognosis analysis of abnormal DFI.This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.

Objective:The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer(HSPC).Methods:Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chi-nese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups.The patients in the control group were treated with androgen deprivation therapy(ADT).And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group.The baseline data of the two groups were analyzed.After 36 months of treat-ment,the differences between the two groups were compared in terms of overall survival(OS),prostate-specific antigen(PSA)level,PSA response rate,Functional Assessment Scale for Prostate Cancer Therapy(FACT-P),Chinese medicine evidence scores,testoster-one level and safety.Results:A total of 80 study subjects were included in this study,including 42 cases in the treatment group and 38 cases in the control group.There was no statistical difference in the baseline data between the two groups before treatment(P＞0.05).At the end of the observation period,a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months(P＜0.05).There was no statistically signif-icant difference in PSA levels in the treatment group at 3 months(P＞0.05).And the differences in the proportion of PSA50(98.1％vs 91.4％),PSA90(92.9％ vs 84.6％)and the proportion of decrease in PSA(56.7％vs 33.8％)in the treatment group were found compared to those in the control group after 6 months of tre atment.After 12 months of treatment,the scores of FACT-4 and re-nal-yang deficiency in the treatment group were(95.28±7.93)and(15.73±5.70)respectively,compared to the scores in the con-trol group([85.46±10.12]and[18.20±4.27](P＜0.05).However,there was no significant difference in serum testosterone([0.60±0.24]nmol/L vs[1.09±2.10]nmol/L)between the two groups(P＞0.05).After 24 months of treatment,there were significant differences in in the FACT-4 total score([97.95±7.54]vs[80.33±8.58]),renal-yang deficiency syndrome score([14.64±5.15]vs[24.94±8.75])between the treatment group and the control group(P＜0.05).However,there was no signifi-cant difference in serum testosterone([0.73±1.01]nmol/L vs[0.59±0.25]nmol/L)between the two groups(P＞0.05).Bet-ter therapeutic results were showed in the treatment group in terms of total FACT-P score,physical situation score,social and family situation score,emotional state score,functional state score,additional score and renal-yang deficiency symptom score(P＜0.05).After treatment,there was no serious adverse reaction in the course of treatment,and no obvious abnormality was found in the liver and kidney function of the patients from two groups.Conclusion:Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients,and the earlier the intervention,the longer the overall survival of the pa-tients.In addition,this treatment regimen can increase the PSA response rate,improve patients'quality of life,and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.