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Modular miniaturized synthesis and in situ biological evaluation facilitate rapid discovery of potent Mra Y inhibitors as antibacterial agents

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Chinese Chemical Letters 2025年第2期36卷 29-31页

作者： Mianling Yang Meehyein Kim Peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology Ministry of Education School of Pharmaceutical SciencesShandong University infectious diseases Therapeutic research Center Korea Research Institute of Chemical Technology (KRICT)

Despite the availability of effective antibacterial drugs, the increasing prevalence of antibiotic-resistant bacteria is primarily attributed to their excessive and inappropriate utilization. Antimicrobial resistance (AMR) represents one of the most concerning global health and development threats [1]. Thereby, the continuous escalation in AMR necessitates urgent advancements in novel antibacterial strategies. The MraY enzyme, which plays a pivotal role in synthesizing bacterial cell wall-composing polysaccharides, holds significant potential as a target for antibacterial agents [2]. However, its conformational dynamics have presented substantial challenges in developing MraY-targeting inhibitors.

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Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

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World Journal of Gastroenterology 2025年第3期31卷 134-137页

作者： Qi-Rong Jiang Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of infectious diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350004Fujian ProvinceChina

In this article,we provide commentary on the recent article by Zhao et *** focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and *** comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy *** gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome ***,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated *** these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal *** conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

关键词： Hepatitis B virus Cirrhosis Portal hypertension Hepatic encephalopathy Transjugular intrahepatic portosystemic shunt Gut microbiota

Mechanism study of the molluscicide candidate PBQ on Pomacea canaliculata using a viscosity-sensitive fluorescent probe

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Chinese Chemical Letters 2025年第1期36卷 447-452页

作者： Lanyun Zhang Weisi Wang Yu-Qiang Zhao Rui Huang Yuxun Lu Ying Chen Liping Duan Ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and TechnologyYunnan UniversityKunming 650091China National institute of Parasitic diseases Chinese Center for Disease Control and PreventionChinese Center for Tropical Diseases ResearchWHO Centre for Tropical DiseasesNational Key Laboratory of Inteligent Tracking and Forecasting for Infectious DiseasesKey Laboratory on Parasite and Vector Biology MinistryofHealthShanghai200025China

PBQ[1-(4-chlorophenyl)-3-(pyridin-3-yl)urea],an enormous potent molluscicide,showed excellent Pomacea canaliculata(***)control activity and low toxicity for other aquatic organisms,but its snail-killing mechanisms are still not fully *** employed an optical method to elucidate PBQ action via a novel fluorescent viscosity probe,*** the viscosity in the test solutions increased,compared with that in pure ethanol,a 54-fold fluorescence intensity enhancement of NCV was observed in 310 cP of 90%***,NCV successfully exhibited a selective fluorescence response towards monensin-induced cellular viscosity changes in HepG2 *** liver,stomach,and foot plantar of the tested snails were frozen and sectioned for fluorescent imaging experiments after the treatment with different PBQ concentrations over various times.A significant fluorescent increase in the snail's liver was observed upon exposure to 0.75 mg/L PBQ for 72 h,which highlighted an increase in *** and eosin(HE)staining further supported PBQ-induced liver damage with a viscosity increase in *** study provides a new rapid optical visualization method to study the killing mechanisms of PBQ and may help discover new chemicals that control snail populations.

关键词： Fluorescence sensor Viscosity Pomacea canaliculata Molluscicide mechanisms Bio-imaging

C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

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World Journal of Gastroenterology 2025年第3期31卷 73-83页

作者： Zhen-Yu Xu Zhong-Shang Dai Guo-Zhong Gong Min Zhang Department of infectious diseases Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina institute of Hepatology and Department of infectious diseases The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell *** their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully *** study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for *** To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for *** This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α*** were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of *** samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell *** Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(Pustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 level

关键词： C-X-C chemokine receptor type 5 Programmed death-ligand 1 Interleukin-21 Pegylated interferon-alpha Chronic hepatitis B

An insect cell-derived extracellular vesicle-based gB vaccine elicits robust adaptive immune responses against Epstein-Barr virus

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Science China Life Sciences 2025年第3期 734-745页

作者： Qian Wu Kaiyun Chen Wenhui Xue Guosong Wang Yanbo Yang Shaowei Li Ningshao Xia Yixin Chen State Key Laboratory of Vaccines for infectious diseases National Institute of Diagnostics and Vaccine Development in Infectious Diseases Collaborative Innovation Center of Biologic Products National Innovation Platform for Industry-Education Integration in Vaccine Research School of Life Sciences School of Public Health Xiang An Biomedicine Laboratory Xiamen University

Epstein-Barr virus(EBV), the first identified human tumor virus, is implicated in various human malignancies, infectious mononucleosis,and more recently, multiple sclerosis. Prophylactic vaccines have the potential to effectively prevent EBV infection. Glycoprotein B(gB)serves as the fusogen and plays a pivotal role in the virus entry process, making it a critical target for EBV vaccine development. Surface membrane proteins of enveloped viruses serve as native conformational antigens, making them susceptible to immune recognition. Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context. In this study, we employed a truncated design for gB proteins, observing that these truncated gB proteins prompted a substantial release of extracellular vesicles(EVs) in insect cells. We verified that EVs exhibited abundant gB proteins, displaying the typical virus particle morphology and extracellular vesicle characteristics. gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice. Moreover, the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity. Consequently, gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.

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Serum ECM1 is a promising biomarker for staging and monitoring fibrosis in patients with chronic hepatitis B

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Science China(Life Sciences) 2025年第2期68卷 431-440页

作者： Lian Liu Danyan Zhang Rong Fan Shipeng Cheng Jichao Yang Liyan Ma Zhiyang Ling Yaguang Zhang Jinlin Hou Xiaomei Wang Bing Sun Junqi Niu Shanghai institute of Biochemistry and Cell Biology Centre for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of infectious Disease Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Med-X institute Centre for Immunological and Metabolic DiseasesThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong UniversityXi’an 710061China Hepatology Department Centre of Infectious Diseases and Pathogen BiologyFirst Hospital of Jilin UniversityChangchun 130021China

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments,but its diagnostic methods remain *** matrix protein 1(ECM1)has previously been reported to be a key factor in the induction and progression of liver ***,little is known about the use of ECM1 as a biomarker to evaluate *** a CCl_(4)-induced mouse model of liver fibrosis,the present study demonstrated that ECM1 decreased with gradually increasing *** biopsy as a reference,the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis,but there were no significant changes between fibrosis stage 2 and stage 0–*** improve the performance of ECM1,age,platelet count,and ECM1 concentration were combined to calculate an EPA(ECM1-platelet-age)score(ranging from 0 to 10).The areas under the receiver operating characteristic curve of the EPA scores for the detection of F≥2,F≥3,and F4 were 0.6801,0.7377,and 0.8083,respectively,which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio,APRI score,or FIB-4 *** HBV patients following antiviral treatment,the dynamics of the EPA score depended on the status of liver fibrosis *** accuracy of the EPA score in predicting fibrosis regression and progression was 66.00%and 71.43%,respectively,while that of the LSM,another useful method for monitoring hepatic fibrosis changes during treatment,was only 52.00%and 7.14%,*** with healthy controls,there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection,MAFLD,ALD,PBC,and *** findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury,and further examinations or medical care are *** conclusion,the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liv

关键词： ECM1 EPA score noninvasive biomarker dynamic liver fibrosis injury

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Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and metaanalysis

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World Journal of Hepatology 2025年第1期17卷 96-111页

作者： Xiao-Tong Xu Min-Jie Jiang Yun-Lai Fu Fang Xie Jian-Jun Li Qing-Hua Meng Beijing institute of Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Interventional Therapy Center for Oncology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Department of infectious diseases Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina

BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are *** To study the gut microbiota characteristics of patients with liver cirrhosis with and without *** We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut *** to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without *** data were analyzed using RevMan and *** Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic *** The gut microbiomes of patients with liver cirrhosis with and without HE *** gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.

关键词： Gut microbiome Cirrhosis Hepatic encephalopathy Review Meta-analysis

Dietary supplementation with citrus peel extract in transition period improves rumen microbial composition and ameliorates energy metabolism and lactation performance of dairy cows

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Journal of Animal Science and Biotechnology 2025年第1期16卷 441-454页

作者： Lingxue Ju Qi Shao Zhiyuan Fang Erminio Trevisi Meng Chen Yuxiang Song Wenwen Gao Lin Lei Xinwei Li Guowen Liu Xiliang Du State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun 130062China Department of Animal Sciences Food and NutritionFaculty of AgricultureFood and Environmental ScienceUniversitàCattolica del Sacro CuorePiacenza 29122Italy

Background During the transition period,excessive negative energy balance(NEB)lead to metabolic disorders and reduced milk *** microbes are responsible for resolving plant material and producing volatile fatty acids(VFA),which are the primary energy source for *** this study,we aimed to investigate the effect of citrus peel extract(CPE)supplementation on rumen microbiota composition,energy metabolism and milk performance of peri-partum dairy *** Dairy cows were fed either a basal diet(CON group)or the same basal diet supplemented with CPE via intragastric administration(4 g/d,CPE group)for 6 weeks(3 weeks before and 3 weeks after calving;n=15 per group).Samples of serum,milk,rumen fluid,adipose tissue,and liver were collected to assess the effects of CPE on rumen microbiota composition,rumen fermentation parameters,milk performance,and energy metabolic status of dairy *** CPE supplementation led to an increase in milk yield,milk protein and lactose contents,and serum glucose levels,while reduced serum concentrations of non-esterified fatty acid,β-hydroxybutyric acid,insulin,aspartate aminotransferase,alanine aminotransferase,and haptoglobin during the first month of *** supplemen-tation also increased the content of ruminal *** to the CON group,the abundance of Prevotellaceae,Methanobacteriaceae,Bacteroidales_RF16_group,and Selenomonadaceae was found increased,while the abun-dance of Oscillospiraceae,F082,Ruminococcaceae,Christensenellaceae,Muribaculaceae UCG-011,Saccharimona-daceae,Hungateiclostridiaceae,and Spirochaetaceae in the CPE group was found *** adipose tissue,CPE supplementation decreased lipolysis,and inflammatory response,while increased insulin *** the liver,CPE supplementation decreased lipid accumulation,increased insulin sensitivity,and upregulated expression of genes involved in *** Our findings suggest that CPE supplementation during the peripartum period

关键词： Adipose tissue Citrus peel extract Energy metabolism Liver Rumen microbiota

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Construction of a lightweight, bispecific human antibody based on the bovine nano knob domain

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Science China Life Sciences 2025年第3期 877-879页

作者： Siling Wang Yizhen Wang Xiuting Chen Wenling Jiang Zheng Chen Huixian Shang Zhiyong Li Zizheng Zheng Ningshao Xia State Key Laboratory of Vaccines for infectious diseases Xiang An Biomedicine Laboratory Department of Laboratory Medicine School of Public Health Xiamen University National institute of Diagnostics and Vaccine Development in infectious diseases State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine Research NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology School of Public Health School of Life Sciences Xiamen University Department of Laboratory Medicine The First Affiliated Hospital of Xiamen University

Dear Editors,Bispecific antibodies (bsAbs), which possess the unique ability to bind to two different antigens simultaneously (Labrijn et al., 2019), have emerged as powerful tools in the field of cancer immunotherapy and pathogen prevention. Their design and production are of great significance, as they can enhance the effectiveness of targeted therapy by improving the accuracy and efficiency of attacks against multiple targets.

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