Abstract:Objective To study the secondary metabolites of Scopulariopsis sp.H3A2,an endophytic fungus isolated from mangrove trees in Malaysia.Methods Silica gel and octadecylsilane(ODS)column chromatography,as well as high-performance liquid chromatography(HPLC),were used to isolate and purify the crude extract from the solid fermentation of the rice strain.The structures of all compounds were determined by analyzing nuclear magnetic resonance(NMR)and mass spectrometry(MS)data and comparing them with literature data.Meanwhile,the antibacterial activity of the compounds against Staphylococcus aureus,Escherichia coli,Micrococcus luteus,Enterococcus faecalis,Candida albicans,and Aspergillus niger was tested by the double dilution method.Results Ten compounds were isolated from the rice solid fermentation crude extract of the strain.The structures of all compounds were determined to be 5,7-dihydroxy-3,4-dihydro-1(2H)-naphthalenone(1),2′-deoxythymidine(2),4,6,8-trihydroxytetralin-1-one(3),3,4,6,8-tetrahydroxy-3,4-dihydro-2H-naphthalen-1-one(4),6-hydroxymellein(5),cyclo(L-Leu-trans-4-hydroxy-L-Pro)(6),cyclo(L-Phe-trans-4-hydroxy-L-Pro)(7),indole-3-carboxylic acid(8),indole-3-carboxaldehyde(9),and 4-hydroxybenzaldehyde(10).The minimum inhibitory concentrations of compounds 1 to 10 are all greater than or equal to 128 mg/L.Conclusion Compounds 1-7 and 10 were isolated from the Scopulariopsis sp.for the first time,and the NMR data of compound 1 was reported for the first time.Compounds 1 to 10 showed no antibacterial activity against Staphylococcus aureus,Escherichia coli,Micrococcus luteus,Enterococcus faecalis,Candida albicans,and Aspergillus niger.

Abstract:Depression is a common mental disorder.Immune imbalance in the peripheral immune system,central nervous system,and gastrointestinal system,and the resulting immune inflammatory response,are significant factors in the pathogenesis of depression.These mechanisms collectively influence the pathological processes of depression through the body's immune regulatory network.Traditional antidepressants possess immunomodulatory functions,while polypeptide drugs and probiotics exert therapeutic potential by targeting immune-neural regulation.This article reviews the relationship between immune imbalance in the peripheral immune system,central nervous system,and gastrointestinal system and the occurrence and development of depression,as well as research progress on immunomodulatory therapy for depression,aiming to explore the role of immune function imbalance in the pathogenesis of depression and to provide references for the immunomodulatory treatment of depression.

Abstract:Protein lactylation plays an important role in the development and progression of various tumors.This modification is involved in multiple biological processes in tumor cells,including the modulation of gene expression,maintenance of chromatin structure,and participation in cell differentiation and development,as well as signal transduction and the regulation of cell cycles.Dysregulation of lactylation may contribute to the silencing of tumor suppressor genes or the activation of oncogenes,potentially leading to tumor initiation and progression.This article provides a comprehensive overview of the impact of protein lactylation on lung,breast,prostate,primary liver,gastric,and colorectal cancers,and highlighting its regulatory effects on the proliferation,metastasis and prognosis of tumor cells,and offers insights into future research directions in this field.

Abstract:Objective This study proposes a deep learning method that integrates edge attention mechanisms and transfer learning to improve segmentation accuracy in mandibular nerve segmentation from oral panoramic images,in order to address the problems of boundary ambiguity and limited training data.Methods The Edge-Guided Attention UNet(EGAUNet)was employed to enhance the ability to capture the edge details of the mandibular nerve in oral panoramic images.Additionally,a transfer learning strategy was integrated to effectively improve the segmentation accuracy under limited training data conditions.Results The method that integrate the edge attention mechanism and transfer learning,was validated using an internal dataset.The experimental results show that after pre-training with transfer learning based on the FIVES dataset,the method obtained the following segmentation performance metrics on the test set of oral panorama data developed in this study:a mean Dice coefficient of 0.711,a recall of 0.725,an intersection over union of 0.575,a positive predictive value of 0.707,and a 95%Hausdorff distance of 12.422.Conclusion The deep learning method that integrates edge attention mechanisms and transfer learning,significantly assist dentists in accurately localizing the mandibular nerve during procedures such as dental implant placement and tooth extraction,thereby reducing the risk of intraoperative nerve injury and enhancing surgical safety.

Abstract:Objective To assess the diagnostic value of texture parameters based on T2-weighted imaging(T2WI)and apparent diffusion coefficient(ADC)maps for clinically significant prostate cancer(csPCa).Methods A total of 187 prostate cancer patients who underwent multiparameter magnetic resonance imaging(mpMRI)were enrolled.Participants were stratified into two groups:39 with Gleason score(GS)<7 and 148 with GS≥7.Texture features were extracted from T2WI and ADC maps using Omni-Kinetic post-processing software and compared between groups.Receiver operating characteristic(ROC)curve analysis assessed the diagnostic performance of texture parameters.Binary logistic regression identified independent predictors of GS≥7.Results Ten texture parameters were calculated for T2WI and ADC maps,including first-order statistics(mean,variance,skewness,energy,entropy,uniformity,kurtosis)and second-order statistics(GLCM energy,GLCM entropy,and GLCM correlation).The differences in T2WI texture parameters mean,variance,kurtosis,GLCM energy,GLCM entropy,and GLCM correlation between prostate cancer with GS<7 group and GS≥7 group were statistically significant.The AUCs of GLCM correlation,GLCM energy,and GLCM entropy are relatively larger,indicating high sensitivity.There was no statistically significant difference between the two groups of skewness,energy,entropy,and uniformity.The texture parameters mean,skewness,uniformity,kurtosis,GLCM energy,GLCM entropy,and GLCM correlation of ADC images showed statistically significant differences.The AUC of mean and uniformity is relatively large,with uniformity having the highest sensitivity and mean having the highest specificity;there was no statistically significant difference in the texture parameters of variance,energy,and entropy between the two groups.Binary logistic regression analysis showed that T2WI texture parameter GLCM entropy and ADC texture parameters uniformity,GLCM energy,and GLCM entropy can used as influencing factors for csPCa identification.When T2WI texture parameters GLCM entropy and ADC texture parameters uniformity,GLCM energy,and GLCM entropy were combined,the diagnostic efficiency is optimal.Conclusion Texture parameters from T2WI and ADC maps serve as non-invasive biomarker for diagnosing csPCa.

Abstract:The human gut microbiota constitutes a vast and complex microbial community.Research indicates that gut microbiota can directly or indirectly participate in the immunomodulation of distal organs through pathways such as its derived metabolites.Furthermore,dysbiosis of gut microbiota,particularly disturbances in its composition,functionality,and structure,is closely associated with the pathogenesis,progression,and treatment of lung diseases.In this review,we delve into the mechanisms by which gut microbiota and its metabolites influence various lung diseases,including asthma,chronic obstructive pulmonary disease,pulmonary fibrosis,tuberculosis,COVID-19,influenza and lung cancer.We also summarize recent advances in emerging therapies based on gut microbiota and its metabolites,thereby providing novel perspectives for targeting gut microbiota in the treatment of lung diseases.

Abstract:Atrial fibrillation(AF)is one of the most common arrhythmias in clinical practice.However,its mechanism has not been fully elucidated,and there are many problems in the treatment of AF,such as high recurrence rate,large side effects and unstable therapeutic effect.In recent years,stem cells have shown great application prospects in the field of cardiovascular disease research and treatment because of their multi-directional differentiation potential and the function of mesenchymal stem cells(MSCs)to secrete exosomes.This article analyzes recent advancements of stem cells in the mechanism and intervention of AF,including the use of stem cells to construct an in vitro AF models,drug screening based on this models,and elucidates molecular mechanisms of AF combined with reprogramming or gene editing technologies.Furthermore,we explore the effect of mesenchymal stem cells on improving myocardial fibrosis by secreting exosomes.It provides a new direction for the treatment of AF in the future.

Abstract:Objective To investigate the efficacy and safety of the combined treatment regimen of Carilizumab,Chemotherapy,and Bevacizumab in Recurrent Metastatic Cervical Cancer(RMCC).Methods A retrospective analysis was carried out on the clinical data of 90 patients diagnosed with RMCC.The patients were divided into two groups based on their treatment regimens:an observation group and a control group,with 45 cases in each group.The control group was treated with paclitaxel,cisplatin,and bevacizumab.Alternatively,the observation group was treated with Carilizumab in addition to paclitaxel,cisplatin and bevacizumab.The efficacy,toxic side effects,cellular immune function indicators,serum tumor markers,and quality of life between the two groups were compared.Results The therapeutic outcomes of the observation group were significantly better than that of the control group(P<0.05).In the toxic side effects of grade 0-1,the observation group exhibited a significantly higher incidence of reactive capillary hyperplasia and thrombocytopenia compared to the control group(P<0.05).The NK cells,CD4+,CD4+/CD8+,CD3+,IgA,IgM,IgG in the observation group were significantly higher than those in the control group after treatment(P<0.01).Moreover,the concentrations of CA125,CA19-9,CEA,and SCC-Ag were evidently reduced in the observation group after treatment compare to the control group(P<0.01).Additionally,the physiological,social,emotional,and functional scores of the observation group after treatment were significantly higher than those of the control group(P<0.05).Conclusion The combination treatment of Carilizumab,chemotherapy,and bevacizumab for RMCC significantly enhance therapeutic efficacy,improve cellular immune function,and elevate quality of life,and reduce serum tumor marker levels,.However,this combination treatment is associated with an increase in grade 0-1 toxic side effects.

Abstract:Objective To explore mediating role of type 2 diabetes mellitus(T2DM)in the association between non-alcoholic fatty liver disease(NAFLD)and its variables.Methods Applied univariate and multivariate Mendelian randomization analyses to explore the relationship between NAFLD and 46 variable factors and to investigate the role of T2DM in mediating this relationship.Results T2DM mediated the association of 7 variables,including high-density lipoprotein cholesterol and obesity assessment index(body mass index,waist circumference,arm fat mass,leg fat mass,total body fat mass,and trunk fat mass),with NAFLD,showing the most significant mediating effect for total body fat mass and NAFLD(mediating effect of 33.90%).Multivariate Mendelian randomization analysis after adjustment for body mass index showed that only high-density lipoprotein cholesterol remained associated with a reduced risk of NAFLD(P<0.05).Conclusion T2DM predominantly mediated the association between high-density lipoprotein cholesterol,obesity assessment metrics and NAFLD,whereas there was no significant causal relationship between other obesity assessment metrics,and NAFLD after adjustment for genetically predicted body mass index.High-density lipoprotein cholesterol may be a key protective factor for NAFLD.

Abstract:As an acute infectious disease transmitted by Aedes mosquitoes,the control of Chikungunya fever faces multiple critical challenges:expanding mosquito distribution,rapid cross-regional transmission and mutation,along with the lack of specific antiviral drugs and widely available vaccines.Developing more effective prevention and control strategies has become a global priority in research.This paper examines the current status of global Chikungunya outbreaks and recent advancements in prevention and control.It systematically reviews key aspects,including pathogen characteristics,epidemiological patterns worldwide,transmission models,mosquito surveillance technologies,and vaccine and antiviral drug development,aiming to provide theoretical foundation for formulating effective control strategies.

Abstract:Objective To investigate the application of endoscopically injected carbon nanoparticles combined with titanium clips in laparoscopic radical resection of colorectal cancer.Methods 100 patients who underwent laparoscopic radical resection of colorectal cancer admitted to Pingxiang Second People's Hospital from January 2023 to June 2024 were included.The patients were divided into an experimental group and a control group using random number table method,with 50 patients in each group.Colonoscopy was performed before operation in both groups,and endoscopic injection of nano-carbon combined with a titanium clip was used before the operation in the experimental group.The localization effect,the total time of operation,the time of probing the lesion during operation,the amount of blood loss,the number of days in the hospital,the incidence of postoperative complications,and the lymph nodes were compared between the two groups.Results The coincidence rates of the ascending colon,hepatic flexion,transverse colon,splenic flexion,descending colon,sigmoid colon,and rectum in experimental group were higher than those in the control group,and the difference was statistically significant(P<0.05).The total operation time,intraoperative lesion exploration time,operative blood loss,and hospitalization days of the experimental group were lower than those of the control group,and the differences were statistically significant(P<0.05).The average number of lymph nodes detected in the experimental group and the average number of tiny lymph nodes detected were higher than those in the control group,and the difference was statistically significant(P<0.05).Conclusion In laparoscopic radical resection of colorectal cancer,nano-carbon combined with titanium clips can accurately locate colorectal cancer,shorten the total time of surgery and intraoperative lesion exploration time,reduce the amount of surgical bleeding,shorten the length of hospital stay,guide the selection of surgical incision,increase the number of lymph nodes detected during surgery,reduce the residue of cancer cells,and facilitate the prognosis of patients,with high clinical value.

Abstract:Chikungunya fever is transmitted by the Chikungunya virus(CHIKV)through mosquito-borne transmission,and its clinical manifestations are highly overlap with those of dengue fever and Zika virus infection,making clinical differential diagnosis difficult.Although viral nucleic acid testing is recognized as a reliable method for early diagnosis,it is difficult to popularize at the grassroots level due to equipment and operational requirements.Serological testing has become the primary diagnostic tool in resource-constrained areas because it is easy to perform and does not require complex instrumentation.In this paper,we systematically review the latest research progress on CHIKV serological testing,and compare the differences in sensitivity,specificity,operation time and genotype coverage among ELISA,Prompt Onset Testing(POCT),Fluorescence Immunosorbent Assay(FLISA),Plaque Neutralisation Test(PRNT),and Modified Pseudo-Virus Neutralisation Test(PVNT).We also focus on the influence of ECSA genotypes on E1-targeted reagents and the diagnostic challenges posed by dengue cross-reactivity,which is prevalent in Guangdong.Focusing on the influence of ECSA genotypes on E1-targeted reagents and the diagnostic challenges of dengue cross-reactivity in Guangdong,we will further explore the clinical application prospects of the modified PRNT and PVNT.Taking into account the characteristics of regional resource distribution,a graded testing strategy of"primary screening by POCT at the grassroots level,batch confirmation by ELISA at the municipal level,and neutralising antibody review by PVNT at the provincial level"was proposed,which provides an evidence-based basis for accurate diagnosis and joint prevention and control of CHIKV in Guangdong and other regions with significant resource differences.It provides an evidence-based foundation for the accurate diagnosis and joint prevention and control of CHIKV in Guangdong and other areas with significant resource disparities.

Abstract:Chikungunya fever is a mosquito-borne infectious disease caused by the Chikungunya virus,which is characterized by joint pain,arthritis,and rashes,and may also be accompanied by neurological problems.Currently,there is currently no approved specific drug or vaccine.To promote the research on the diagnosis and treatment of Chikungunya fever,this review summarizes the research progress on Chikungunya virus,including its epidemiology,pathology,diagnosis,and treatment methods,in order to provide a comprehensive reference for in-depth research and effective prevention and control strategies of Chikungunya fever.

Abstract:Objective This study aimed to investigate the function and mechanism of Galectin-1(Gal-1)in lung adenocarcinoma.Methods ⑴Database information analysis:The relationship between Gal-1 expression level and patient prognosis was analyzed using the TCGA-LUAD database.⑵ In vitro cell experiments:①Lung adenocarcinoma cells A549 and H1299 were transfected with siRNA and divided into two groups:the Negative control(NC)group and the experimental group(siLGALS1-1,siLGALS1-2).The effects of Gal-1 on the proliferation of lung adenocarcinoma cells were explored using cell counting kit-8(CCK-8)proliferation assay and the colony formation assay.②The effects of Gal-1 on the migration and invasion of lung adenocarcinoma cells were explored using Transwell migration and invasion assays and a wound healing assay.⑶Molecular mechanism experiments:The downstream molecular mechanisms of Gal-1 were explored through enrichment pathway analysis and rescue experiments.⑷In vivo animal experiments:Lung adenocarcinoma cells from the NC group and the stable low-expression LGALS1 group were injected subcutaneously into 4-week-old female BALB/c nude mice,with 5 mice in each group,for a total of 10 mice.The in vivo biological function of Gal-1 in the lung adenocarcinoma model was verified by constructing a subcutaneous tumor model and performing immunohistochemistry experiments.⑸Clinical sample verification:The total RNA and total protein expression levels of Gal-1 in lung adenocarcinoma tissues and adjacent tissues were detected by qRT-PCR and Western blot analyses.Results ⑴ The results of the bioinformatics analysis of the TCGA-LUAD database showed that high expression of Gal-1 mRNA was associated with poor prognosis for patients(P<0.05).⑵ In vitro experiments showed that,compared with the NC group,Gal-1 knockdown significantly suppressed the proliferative ability of lung adenocarcinoma cells(P<0.001),significantly inhibited their colony-forming ability(P<0.01),and significantly inhibited their migratory and invasive abilities(P<0.05),while Gal-1 overexpression promoted tumor cell proliferation(P<0.001)and metastasis(P<0.05).⑶ Gal-1-related differentially expressed genes were enriched in the AKT/mTOR signaling pathway.The phosphorylation levels of AKT and mTOR were increased in lung adenocarcinoma cells overexpressing Gal-1,and the use of rescue experiments demonstrated that pharmacological inhibition of mTOR effectively attenuates the oncogenic effects induced by Gal-1 overexpression(P<0.01).⑷ Compared with the NC group,the subcutaneous tumor growth rate,subcutaneous tumor volume,and weight of mice in the stable low-expression LGALS1 group were significantly reduced(P<0.05),and the Ki67 expression level as well as the phosphorylation levels of AKT and mTOR in the subcutaneous tumor tissue of mice were reduced.⑸ Clinical sample validation showed that,compared with adjacent tissues,the levels of Gal-1 RNA and protein in lung adenocarcinoma tissues were significantly increased(P<0.001).Conclusion Gal-1 acts as a critical oncogenic regulator in lung adenocarcinoma and potentially promotes tumor cell proliferation and metastasis by activating the AKT/mTOR signaling pathway.

Abstract:Objective To establish a chronic lipopolysaccharide(LPS)-induced animal model for mechanistic research of major depressive disorder(MDD)-cognitive dysfunction comorbidity.Methods Male C57BL/6J mice were randomly divided into two groups(n=10 per group):a control group,which intraperitoneal injection of 0.9%normal saline and an LPS group,intraperitoneal injection of LPS(0.5 mg/kg).Both injections were administered continuously for 10 days.After the injection period,the depressive-like behavioral phenotypes of the mice were evaluated using animal behavioral paradigms,including the open field test(OFT),sucrose preference test(SPT),forced swim test(FST).Short-term spatial memory performance,related to concurrent cognitive function,was evaluated using the Y-maze test.Results Compared with the control mice,mice subjected to chronic LPS administration showed significantly decreased body mass,sucrose preference,spatial preference memory,and reduced locomotor activity.Furthermore,immobility time in the forced swim test was significantly increased(P<0.05).Conclusion Behavioral assessments validate chronic LPS-induced paradigm as preclinical model of MDD-cognitive dysfunction comorbidity.

Abstract:Objective To analyze the distribution characteristics and epidemiological trends of the pathogen spectrum in children under 14 years old with acute respiratory tract infections(ARTI)in Shenzhen,aiming to guide clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 5 669 children hospitalized with a clinically diagnosed of ARTI between January 8,2023,and January 8,2024,in municipal and district-level hospitals in Shenzhen,including Bao'an District People's Hospital.Throat swabs or bronchoalveolar lavage fluid specimens collected during initial visits were tested for 198 common pathogens using targeted next-generation sequencing.The composition of respiratory pathogen spectra,mixed infections,severe cases,and pathogen detection rates stratified by gender,age groups,and seasons were analyzed.Results The most frequency detected pathogens in Shenzhen children with ARTI were Haemophilus influenzae(32.2%),Mycoplasma pneumoniae(30.6%),rhinovirus(22.3%),Streptococcus pneumoniae(18.1%),and Moraxella catarrhalis(17.2%).Mixed infections(defined as≥2 pathogens)accounted for 82.8%(4 695/5 669)of cases,while severe pneumonia cases comprised 1.1%(64/5 699).Detection rates of H.influenzae,M.pneumoniae,and respiratory syncytial virus(RSV)were significantly higher in male patients than in females(P<0.05).By age groups,RSV was most common in neonates(<1 month),infants(1 month to<1 year),and toddlers(1 to<3 years).H.influenzae was predominant in preschoolers(3 to<7 years),while M.pneumoniae was most prevalent in school-aged children(7-14 years).Seasonal analysis showed that M.pneumoniae dominated in spring,summer,and winter,whereas H.influenzae was most frequent in autumn.Conclusion H.influenzae was the leading bacterial pathogen,rhinovirus the predominant viral agent,and M.pneumoniae remains highly prevalent among children in Shenzhen.Bacterial and M.pneumoniae co-infections are the primary mixed infection pattern.Note:Scientific names of pathogens are italicized,and statistical values/p-values are formatted per standard medical writing conventions.was mainly bacterial and MP mixed infection.

Abstract:Objective To determine the median effective dose(ED50)of remimazolam for suppressing tracheal intubation-induced responses during thyroid surgery under recurrent laryngeal nerve monitoring,when combined with cisatracurium at twice its 95%effective dose(2×ED95).Methods In this prospective study,56 ASA Ⅰ-Ⅱ patients scheduled for elective thyroidectomy with intraoperative nerve monitoring between July 2023 and February 2024 were enrolled.The remimazolam dose was determined using a biased-coin up-and-down sequential method,starting at 0.3 mg/kg.After achieving a BIS≤60 and a Modified Observer's Assessment of Alertness/Sedation(MOAA/S)score≤1,patients received cisatracurium 0.1 mg/kg(2×ED95)and sufentanil 0.4 μg/kg.Intubation was performed 5 minutes later using video laryngoscopy.The remimazolam dose for subsequent patients was adjusted based on the cardiovascular response observed during intubation.Probit regression was used to calculate ED50,ED95,and 95%CI.Hemodynamic variables including systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),bispectral index(BIS),blood oxygen saturation of pulse(SpO2)were recorded at four time points:T0(baseline),T1(pre-intubation),T2(30 seconds post-cuff inflation),and T3(3 minutes post-intubation).Intubation conditions,time to nerve monitoring,and perioperative adverse events were also assessed.Based on the occurrence of an intubation response,subjects were divided into positive and negative groups,and the remimazolam dosage and BIS differences at T1 were compared between the two groups.Results The ED50 of remimazolam for suppressing tracheal intubation-induced hemodynamic responses was 0.287 mg/kg(95%CI:0.249-0.296 mg/kg),and the ED95 was 0.310 mg/kg(95%CI:0.304-0.422 mg/kg).MAP significantly decreased from T1 to T3 compared with T0,HR was reduced at T1 and T3,and SpO₂ increased across the same intervals(all P<0.05).No statistically significant difference in remimazolam doses was observed between the two groups(P>0.05),and BIS values were all<60 before intubation(indicating adequate sedation).Postoperative adverse events included 2 cases of nausea and vomiting,1 case of sore throat,and 1 case of hypotension.No instances of intraoperative awareness or intubation failure were observed.Conclusion During thyroid surgery with recurrent laryngeal nerve monitoring,the ED50 of remimazolam for suppressing tracheal intubation-induced hemodynamic responses was determined to be 0.287 mg/kg when combined with cisatracurium at 2×ED95.

Abstract:Objective To investigate the mechanism of Xiaoluowan(XLW)against liver fibrosis based on network pharmacology and animal experiments.Methods The active components of XLW and their potential targets were screened using TCMSP and HERB databases.Liver fibrosis-related targets were obtained from GeneCards,DisGeNET,and OMIM databases.The overlapping targets were analyzed via protein-protein interaction(PPI)networks on the STRING platform,followed by Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis using Metascape.Visualization was performed with Cytoscape.For animal experiments,24 male C57BL/6 mice(6-8 weeks old)were randomly divided into control,model,and XLW groups(n=8 per group).Liver fibrosis was induced by carbon tetrachloride(CCl4)for 8 weeks.From the 5th week onward,the XLW group received daily oral gavage of XLW decoction(5.4 mL/kg),while control and model groups received equal volume saline.After 8 weeks,mice were sacrificed to assess liver-to-body weight ratio,serum ALT/AST levels,liver pathology(histological staining),and hepatic PI3K/Akt pathway protein expression(Western blot).Results A total of 388 XLW-related targets and 3 943 liver fibrosis-related targets were identified,with 242 overlapping targets.Core targets included AKT1,TNF,TP53,and PTGS2.KEGG enrichment analysis revealed that the PI3K/Akt signaling pathway and pathways in cancer as the most significantly enriched.XLW treatment markedly reduced the liver-to-body weight ratio,improved liver function,attenuated collagen deposition,and downregulated PI3K and Akt protein expression(P<0.05).Conclusion XLW exerts anti-fibrotic effects by modulating AKT1 core targets and inhibiting the PI3K/Akt signaling pathway.

Abstract:Objective To investigate the neuroprotective effects and underlying mechanisms of the lipid-lowering drug Ezetimibe(Eze)in a Parkinson's disease(PD)model.Methods In vitro,BV-2 murine microglial cells were divided into blank,MPP⁺,and Eze+MPP⁺ groups,and cell viability was measured.Male C57BL/6J mice were used to establish a Parkinson's disease model induced by MPTP.Thirty-six healthy male mice were randomly allocated into three groups(n=12 per group):Control,receiving daily intraperitoneal saline for 5 weeks;MPTP,receiving 25 mg/kg MPTP intraperitoneally twice weekly for 5 weeks;and MPTP+Eze,receiving the same MPTP schedule plus daily intraperitoneal Eze at 10 mg/kg for 5 weeks.Twenty-four hours after the last administration,motor performance was evaluated using the pole,rotarod,and grip-strength tests.The animals were then euthanized,and substantia nigra tissue was collected.Western blot was performed to measure protein levels of nuclear factor erythroid 2-related factor 2(Nrf2),triggering receptor expressed on myeloid cells 2(TREM2),tyrosine hydroxylase(TH),and ionized calcium-binding adapter molecule 1(IBA-1).Interleukin-1 beta(IL-1β)content was determined by Enzyme-Linked Immunosorbent Assay(ELISA),and immunofluorescence staining was used to assess microglial activation.Results In vitro,Eze significantly increased the viability of MPP⁺-challenged BV-2 cells(P<0.05).In vivo,compared with the MPTP group,the MPTP+Eze group showed significant upregulation of Nrf2(P<0.05)and TREM2(P<0.01)expression,suppression of IBA-1 expression,reduced IL-1β secretion(P<0.01),increased TH ⁺ neuron counts(P<0.01),and improved motor performance in pole-climbing,rotarod,and grip strength assays(P<0.05).Conclusion Eze exerts neuroprotective effects on dopaminergic neurons by activating the Nrf2/TREM2 signaling pathway,leading to alleviate oxidative stress and neuroinflammation.

Abstract:Chikungunya fever is an acute mosquito-borne infectious disease caused by the Chikungunya virus(CHIKV),characterized by symptoms such as fever,arthralgia,and rash.Some patients may develop chronic joint pain.CHIKV can be divided into three main genotypes:West African,East/Central/South African,and Asian.Continued mutation during transmission affects the virus's pathogenicity and transmissibility.Currently,significant progress has been made in developing CHIKV vaccines.The live-attenuated vaccine IXCHIQ and the virus-like particle vaccine VIMKUNYA have been approved,and a variety of candidate vaccines such as inactivated vaccines,viral vector vaccines,and nucleic acid vaccines,are in clinical trials.This article reviews the viral characteristics,genetic evolution,and pathogenic mechanisms of CHIKV,as well as the progress of clinical research on vaccines,to provide a reference for future studies on its pathogenesis and vaccine development.