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SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broadspectrum antifungal agent

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Plant Communications 2024年第2期5卷 169-184页

作者： xi-Yu Wu Bo Dong Xue-Ming Zhu Ying-Ying Cai lin Li Jian-Ping {2. Bin Yu Jing-Li Cheng Fei Xu Jian-Dong Bao Ying Wang xiao-Hong Liu Fu-Cheng lin State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of BiotechnologyZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Plant Protection and MicrobiologyZhejiang Academy of Agricultural SciencesHangzhou 310058Zhejiang ProvinceChina department of Pharmacology and Nutritional Science College of MedicineThe University of KentuckyLexingtonKY 40506USA Markey Cancer Center College of MedicineThe University of KentuckyLexingtonKY 40506USA College of Life Sciences Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Institute of Pesticide and Environmental Toxicology Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and InsectsZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Institute of Edible Fungi Shanghai Academy of Agricultural SciencesShanghai 201106ShanghaiChina

Rice blast is a devastating disease worldwide,threatening rice production and food *** blast fun-gus Magnaporthe oryzae invades the host via the appressorium,a specialized pressure-generating struc-ture that generates enormous turgor pressure to penetrate the host ***,owing to ongoing evolution of fungicide resistance,it is vitally important to identify new targets and ***,we show that Trs85,a subunit of the transport protein particle III complex,is essential for appressorium-mediated infection in *** explain how Trs85 regulates autophagy through Ypt1(a small guano-sine triphosphatase protein)in *** then identify a key conserved amphipathic a helix within Trs85 that is associated with pathogenicity of *** computer-aided screening,we identify a lead compound,SP-141,that affects autophagy and the Trs85–Ypt1 ***-141 demonstrates a substantial capacity to effectively inhibit infection caused by the rice blast fungus while also exhibiting wide-ranging potential as an antifungal agent with broad-spectrum *** together,our data show that Trs85 is a potential new target and that SP-141 has potential for the control of rice *** thus provide a novel strategy that may help in thefight against rice blast.

关键词： Magnaporthe oryzae rice blast TRAPPIII complex trs85 fungicide

Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3543-3560页

作者： Lixin Zhao Yuguang Zhu Hua Tao xiying Chen Feng Yin Yingyi Zhang Jianfeng Qin Yongyin Huang Bikun Cai Yonghao {2. Jiaxiang Wu Yu Zhang lu Liang Ao Shen xi-Yong Yu The Fifth Affiliated Hospital Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical PharmacologyNMPA&State Key LaboratorySchool of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Pulmonary fibrosis poses a significant health threat with very limited therapeutic options *** this study,we reported the enhanced expression of mesenchymal homobox 1(MEOX1)in pulmonary fibrosis patients,especially in their fibroblasts and endothelial cells,and confirmed MEOX1 as a central orchestrator in the activation of profibrotic *** high-throughput screening,we identified Ailanthone(AIL)from a natural compound library as the first small molecule capable of directly targeting and suppressing *** demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-b1(TGF-b1).In an animal model of bleomycin-induced pulmonary fibrosis,AIL effectively mitigated the fibrotic process and restored respiratory ***,AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1,thereby inhibiting MEOX1 expression and *** summary,our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in ***,we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis,specifically through the suppression of JUN-dependent MEOX1 activation.

关键词： Ailanthone MEOX1 Pulmonary fibrosis JUN TGF-b1 High-throughput screening Natural product

Clinical significance of upregulated Rho GTPase activating protein 12.causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4244-4263页

作者： xiao-Wei Wang Yu-xing Tang Fu-xi Li Jia-Le Wang Gao-Peng Yao Da-Tong Zeng Yu-lu Tang Bang-Teng Chi Qin-Yan Su lin-Qing Huang Di-Yuan Qin gang Chen Zhen-Bo Feng Rong-Quan He department of Pathology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina department of Pathology Red Cross Hospital of Yulin CityYulin 537000Guangxi Zhuang Autonomous RegionChi department of Medical Oncology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina department of Computer Science and Technology School of Computer and Electronic InformationGuangxi UniversityNanning 530004Guangxi Zhuang Autonomous RegionChina

BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in *** therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is *** Rho GTPase family member Rho GTPase activating protein 12.ARHGAP12.,which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in ***,no studies on the expression of ARHGAP12.in HCC and its role in resistance to TKIs have been *** To unveil the expression of ARHGAP12.in HCC,its role in TKI resistance and its potential associated *** This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12.mRNA levels and explored its mechanisms through enrichment *** was used to investigate focal adhesion(FA)pathway *** integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12.mRNA and protein levels,correlating with clinical *** assessed ARHGAP12.expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and *** ARHGAP12.mRNA was found to be highly expressed in malignant hepatocytes and to regulate *** malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor ***12.mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse ***12.was also found to be a TKI resistance gene that regulated the FA ***1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk *** expression of ARHGAP12.was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to *** ARHGAP12.expre

关键词： Hepatocellular carcinoma Focal adhesion Tyrosine kinase inhibitor Rho GTPase activating protein 12 Drug resistance Molecular mechanism Biomarker

Sperm acrosin activity may be a useful factor in choosing between ICSI and IVF for infertile male patients

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Asian Journal of Andrology 2024年第1期26卷 85-90页

作者： Ye-Na Hu Liang Hu xin-Yu Yin Huan Zhang Yang-Qin Peng gang Liu Ge {2. Wei-Na Li The Institute of Reproductive and Stem Cell Engineering School of Basic Medical ScienceCentral South UniversityChangsha 410008China department of Andrology Reproductive and Genetic Hospital of CITiC-XiangyaChangsha 410013China Clinical Research Center for Reproduction and Genetics in Hunan Province Changsha 410013China Hunan Guangxiu Hi-tech Life Technology Co. Ltd.Changsha 410013China

The clinical applications of acrosin activity are *** analyzed 61578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-{2.angya(Changsha,China)between August 2.14 and December 2.19 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men;to determine whether correlations e{2.st between acrosin activity and age,sperm concentration,sperm morphology,or sperm motility;and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization(IvF)and intracytoplasmic sperm injection(icsl)in the *** cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 2..78μlu per 106 *** was no significant association between acrosin activity and age,sperm concentration,semen volume,total sperm count,progressive motility,or total motile spermatozoa.A weak positive correlation was found between acrosin activity and normal sperm *** was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity(>2..78μlu per 106 sperm)and the group with low acrosin activity(2..78μlu per 106 sperm).The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 2..2.,while the group with a high IVF fertilization rate had a low index of 0.2..At an acrosin activity of2..78μlu per 10 sperm,in one cycle of the same patient,the fertilization rate,normal fertilization rate,and good-quality embryo rate for Icsl were significantly higher than those for ***,the most promising application of acrosin activity could be in the selection of IcsI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

关键词： acrosin activity fertilization rate ICSI IVF semen parameters

Expert consensus on endodontic therapy for patients withsystemic conditions

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International Journal of Oral Science 2024年第3期16卷 390-397页

作者： xin Xu xin Zheng Fei {2. Qing Yu Benxiang Hou Zhi Chen xi Wei Lihong Qiu Wenxia Chen Jiyao Li Lili Chen Zuomin Wang Hongkun Wu Zhiyue lu Jizhi Zhao Yuhong Liang Jin Zhao Yihuai Pan Shuang Pan xiaoyan Wang Deqin Yang Yanfang Ren {2. Yue Xuedong Zhou State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital StomatologyPeking UniversityBeijingChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of Oral DiseasesDepartment of Operative Dentistry&EndodonticsSchool of StomatologyThe Fourth Military Medical UniversityXi’anChina Center for Microscope Enhanced Dentistry Beijing Stomatological HospitalCapital Medical UniversityBeijingChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina department of Endodontics School of StomatologyChina Medical UniversityShenyangChina College&Hospital of Stomatology Guangxi Medical UniversityNanningChina department of Stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina department of Stomatology Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&department of Geriatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina Beijing Hospital National Center of GerontologyBeijingChina department of Stomatology Peking Union Medical College Hospit

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. Asystemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining thenecessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is acollaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontictherapy in patients with compromised overall health.

关键词： patients diagnosis prognosis

Clinical efficacy and identification of factors confer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3130-3140页

作者： Yanni Wang Chang Liu Huan Chen xi Jiao Yujiao Wang Yanshuo Cao Jian Li xiaotian Zhang Yu Sun Na Zhuo Fengxiao Dong Mengting Gao Fengyuan Wang Liyuan Dong Jifang Gong Tianqi Sun Wei Zhu Henghui Zhang lin Shen Zhihao lu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Genecast Biotechnology Co. LtdWuxiPR China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijingChina Precision Scientific(Beijing)Co. Ltd.BeijingChina Generulor Company Bio-X Lab ZhuhaiGuangdongChina Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory for Therapeutic Cancer Vaccines Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival *** preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing *** proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable to{2.city *** analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2.NTRK2.was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR ***,knocking down or inhibiting NTRK2.sensitized ESCC cells to afatinib *** study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

关键词： esophageal squamous expressing

Effects of COL1A1 and SYTL2.on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm

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Chinese Medical Journal 2024年第9期137卷 1105-1114页

作者： xinsheng xie Ye Yuan Yulong Huang xiang Hong Shichai Hong gang Chen Yihui Chen Yue lin Weifeng lu Weiguo Fu Lixin Wang department of Vascular Surgery Zhongshan Hospital(Xiamen)Fudan UniversityXiamenFujian 361015China department of Vascular Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Vascular Surgery Institute of Fudan university Fudan UniversityShanghai 200032China

Background:Thoracic aortic aneurysm(TAA)is a fatal cardiovascular disease,the pathogenesis of which has not yet been *** study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this ***:Gene expression profiles of the GSE9106,GSE2.155,and GSE155468 datasets were acquired from the Gene Expression Omnibus(GEO)*** expressed genes(DEGs)were identified using the"limma"package in *** absolute shrinkage and selection operator(LASSO),support vector machine-recursive feature elimination(SVM-RFE),random forest,and binary logistic regression analyses were used to screen the diagnostic marker ***-sample gene set enrichment analysis(ssGSEA)was used to estimate immune cell infiltration in ***:A total of 16 DEGs were *** enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related *** type I alpha 1 chain(COL1A1)and synaptotagmin like 2.SYTL2.were identified as diagnostic marker genes with a high diagnostic value for *** expression of COL1A1 and SYTL2.was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues,and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall ***,COL1A1 and SYTL2.expression were associated with the infiltration of immune cells in the vascular wall ***-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2.mainly from cluster of differentiation(CD)8+T *** addition,single-cell analysis indicated that fibroblasts and CD8+T cells in TAA were significantly higher than those in normal arterial wall ***:COL1A1 and SYTL2.may serve as diagnostic marker genes for *** upregulation of SYTL2.and COL1A1 may be involved in the inflammat

关键词： Bioinformatics Thoracic aortic aneurysm Immune response Single cell analysis Machine learning

Analysis of status and influencing factors of mental health in patients with systemic lupus erythematosus

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World Journal of Psychiatry 2024年第6期14卷 829-837页

作者： Xuan Zhang Zhe Wang Gui-ling lin Fang-Zhi Wei Yan-Ping Zhuang Wen-{2. Xu Qi Zhang Hui-Tao Wu Zi-Man He xi-Yu Yin Ying Liu Long Mi Ai-Min Gong School of Traditional Chinese Medicine Hainan Medical UniversityHaikou 571101Hainan ProvinceChina department of Rheumatology and Immunology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311Hainan ProvinceChina department of Radiology The First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityHaikou 570100Hainan ProvinceChina

BACKGROUND Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disorder with varied clinical courses and prognoses,not only did the patients suffer from physical impairment,but also various physical and psychiatric *** evidence have suggested that mental disorders in SLE patients,can lead to various adverse *** To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social *** results would provide a basis for psychological intervention in patients with *** The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical university between June 2.2. and June 2.2. were *** assessment and correlation analysis were conducted using the Symptom Checklist-90(SCL-90)and Perceived Social Support Scale,and the collected data were compared with the national norms in *** relevant factors influencing mental health were identified by statistical analysis.A general information questionnaire,the Revised Life Orientation Test,and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life(QoL),*** Patients with SLE obtained higher scores for the somatization,depression,anxiety,and phobic anxiety subscales than national norms(P2.and 30 cases were in the middle and lower levels.A positive correlation was found between optimism level and QoL *** Patients with SLE develop psychological disorders at varying degrees,which are significantly influenced by hormone dosage and ***’menta

关键词： Systemic lupus erythematosus Mental health Quality of life Influencing factors

Myelin oligodendrocyte glycoprotein-associated transverse myelitis after SARS-CoV-2.infection:A case report

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World Journal of Radiology 2024年第9期16卷 446-452页

作者： Jian-Rong Zheng Jun-Lei Chang Jun Hu Zhi-Jian lin Kai-Hua lin Bi-Hua {2. Xu-Hui Chen Zhi-gang Liu department of Neurology Peking University Shenzhen HospitalShenzhen 518000Guangdong ProvinceChina department of Neurology Shenzhen Xinhua HospitalShenzhen 518000Guangdong ProvinceChina Institute of Biomedicine and Biotechnology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518000Guangdong ProvinceChina department of Neurology The Sixth People’s Hospital of Foshan Nanhai DistrictFoshan 528000Guangdong ProvinceChina Laboratory of Functional chemistry and Nutrition of Food Northwest A&F UniversityYangling 712100Shaanxi ProvinceChina

BACKGROUND Cases of myelin oligodendrocyte glycoprotein(MOG)antibody-related disease have a history of coronavirus disease 2.19 infection or its vaccination before disease *** acute respiratory syndrome virus 2.SARS-CoV-2.infection has been considered to be a trigger of central nervous system autoimmune *** SUMMARY Here we report a 2.-year male with MOG-associated transverse myelitis after a SARS-CoV-2.*** patient received a near-complete recovery after standard immunological *** Attention should be paid to the evaluation of typical or atypical neurological symptoms that may be triggered by SARS-CoV-2.infection.

关键词： Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis Myelin oligodendrocyte glycoprotein antibody-associated disease SARS-CoV-2 COVID-19 Case report