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aBIOTECH 2024年第2期5卷 219-224页

作者： Yun Zhang Miao-Miao Cui Run-Nan Ke Yue-Dan Chen Kabin Xie National key laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China Hubei key laboratory of Plant pathology Huazhong Agricultural UniversityWuhan 430070China

Loss-of-function mutants are fundamental resources for gene function ***,it is difficult to generate viable and heritable knockout mutants for essential ***,we show that targeted editing of the C-terminal sequence of the embryo lethal gene MITOGEN-ACTIVATED PROTEIN KINASES 1(OsMPK1)results in weak *** C-terminal-edited osmpk1 mutants displayed severe developmental defects and altered disease resistance but generated tens of viable seeds that inherited the *** the same C-terminal editing approach,we also obtained viable mutants for a wallassociated protein kinase(Os07g0493200)and a leucine-rich repeat receptor-like protein kinase(Os01g0239700),while the null mutations of these genes were *** data suggest that protein kinase activity could be reduced by introducing frameshift mutations adjacent to the C-terminus,which could generate valuable resources for gene function studies and tune protein kinase activity for signaling pathway engineering.

关键词： CRISPR/Cas9 Lethal mutant Protein kinases Genome editing C-terminus

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

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Cancer Biology & Medicine 2024年第2期21卷 163-174页

作者： Yi Li Bing Wei Xia Xue Hongle Li Jun Li Department of Molecular pathology Clinical Pathology CenterAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou 450003China Henan key laboratory of Molecular pathology Zhengzhou 450003China Henan key laboratory of Helicobacter pylori&Microbiota and Gastrointestinal Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Esophageal cancer(EC)is an aggressive malignancy with a poor *** factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal ***,enrichment and diversity of the esophageal microbiome can also impact its *** studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC ***,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment *** this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and *** the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

关键词： Esophageal cancer microbiome dysbiosis microenvironment carcinogenesis

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

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Current Medical Science 2024年第3期44卷 519-528页

作者： Jia SONG Dong-lei SUN Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong ZHANG Ting-ting YANG Mei SONG Xin-li BAI Xiao-lan ZHANG Department of gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000China Department of Pediatrics The Second Hospital of Hebei Medical UniversityShijiazhuang050000China

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis *** study aimed to explore the effects of TL1A on human colonic *** A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal *** human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)*** proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western *** metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT *** growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT *** proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 ***1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co *** of CCD-18Co cells with TL1A increased the expression of TGF-β1 and *** TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

关键词： tumor necrosis factor ligand-related molecule-1A fibrosis inflammatory bowel disease myofibroblasts transforming growth factor-β1

Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： Yuan Yuan Peiyuan Li jianghui Li Qiu Zhao Ying Chang Xingxing He Department of gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and key laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal *** these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and *** attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing *** evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of *** of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic ***,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： Lipid ation primarily

FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan Liang Xu Lu Shi Xiong Ma Liya Zhou Luyao Wang Jiaojiao Wang Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong Wang Xiaokun Li Yongde Luo Yongping Chen Hepatology Diagnosis and Treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China Division of gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou Medical College Hangzhou 311300China

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 Immune liver injury Ca^(2+)/Calmodulin dependent protein

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Decoding the biochemical dialogue: metabolomic insights into soybean defense strategies against diverse pathogens

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Science China Life Sciences 2024年第10期67卷 2234-2250页

作者： Min Qiu Mengjun Tian Yaru Sun Huaibo Li Wenwen Huang Haibing Ouyang Shaoyan Lin Chen Zhang Ming Wang Yuanchao Wang Sanya Institute of Nanjing Agricultural University Department of Plant PathologyNanjing Agricultural University The key laboratory of Plant Immunity Nanjing Agricultural University key laboratory of Soybean Disease and Pest Control (Ministry of Agriculture and Rural Affairs) Nanjing Agricultural University China State key laboratory of Crop Genetics & Germplasm Enhancement and Utilization Nanjing Agricultural University

Soybean, a crucial global leguminous crop, confronts persistent threats from diverse pathogens, exerting a profound impact on global *** genetic dimensions of soybean-pathogen interactions have garnered attention, the intricate biochemical responses remain poorly elucidated. In this study, we applied targeted and untargeted liquid chromatography coupled to mass spectrometry(LC-MS) metabolite profiling to dissect the complex interplay between soybeans and five distinct pathogens. Our analysis uncovered 627 idMS/MS spectra,leading to the identification of four main modules, encompassing flavonoids, isoflavonoids, triterpenoids, and amino acids and peptides,alongside other compounds such as phenolics. Profound shifts were observed in both primary and secondary metabolism in response to pathogenic infections. Particularly notable were the bidirectional changes in total flavonoids across diverse pathogenic inoculations, while triterpenoids exhibited a general declining trend. Noteworthy among the highly inducible total flavonoids were known representative antipathogen compounds(glyceollin I), backbone forms of isoflavonoids(daidzein, genistein, glycitein, formononetin), and newly purified compounds in this study(prunin). Subsequently, we delved into the biological roles of these five compounds, validating their diverse functions against pathogens: prunin significantly inhibited the vegetative growth and virulence of Phytophthora sojae; genistein exhibited a pronounced inhibitory effect on the vegetative growth and virulence of Phomopsis longicolla; daidzein and formononetin displayed significant repressive effects on the virulence of P. longicolla. This study underscores the potent utility of metabolomic tools, providing in-depth insights into plant-pathogen interactions from a biochemical perspective. The findings not only contribute to plant pathology but also offer strategic pathways for bolstering plant resistance against diseases on a broader scale.

关键词： metabolome soybean soybean-pathogens interaction secondary metabolites triterpenoids flavonoids isoflavonoids antimicrobial compounds

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-Hong Ding Fang Liu Shi-Jie Chen Chen-Kai Huang Meng-Chao Xiao Xia-Lu Hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding Cheng Luo Xin Zhang Wei-Fen Xie Department of gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3471-3480页

作者： Wei-Yang Shu Yan-Yan Shi Jiu-Tian Huang Ling-Mei Meng He-Jun Zhang Rong-Li Cui Yuan Li Shi-Gang Ding Department of gastroenterology Peking University Third HospitalBeijing 100191China Research Center of Clinical Epidemiology Peking University Third HospitalBeijing 10019China Department of gastroenterology pathology laboratory Peking University Third HospitalBeijing 100191China Department of gastroenterology Peking University International HospitalBeijing 102206China

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used *** structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different ***,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'*** To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'*** Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April *** first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical *** images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and *** The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and *** analyses revealed significant differences(aP0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among va

关键词： Esophageal squamous cell carcinoma Intrapapillary capillary loop The Japan Esophageal Society classification Magnifying endoscopy Pathological characteristics

Enhancing the anti-corrosion performance and biocompatibility of AZ91D Mg alloy by applying roughness pretreatment and coating with in-situ Mg(OH)_(2)/Mg-Al LDH

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Journal of Magnesium and Alloys 2024年第6期12卷 2520-2533页

作者： Zexi Shao Pubo Li Chao Zhang Bintao Wu Chan Tang Mangmang Gao School of Materials and New Energy Ningxia Key Laboratory of Photovoltaic MaterialsNingxia UniversityYinchuan750021PR China Department of gastroenterology The Third Xiangya HospitalCentral South UniversityChangsha410000PR China

Corrosion-resistant and biocompatible films were fabricated on AZ91D Mg alloy substrates by varying their roughness levels using met-allographic preparation and subsequent hydrothermal *** coated films comprised a mixed structure of Mg(OH)_(2)and Mg-Al layered double hydroxides(LDH)and exhibited excellent *** film thickness increased with decreasing surface *** resistance was evaluated using potentiodynamic polarization and electrochemical impedance *** pretreat-ment influenced the chemical activity of the Mg alloy surface and helped modulate the dissolution rate of the Mg_(17)Al_(12)phase during the hydrothermal *** decreasing roughness of the Mg substrate,the Al^(3+)concentration gradually increased,accelerating the in-situ formation of the Mg(OH)_(2)/LDH composite coating and improving its crystallinity.A thick and dense Mg(OH)_(2)/LDH coating was synthesized on the Mg substrate with the least roughness,substantially improving the corrosion resistance of the AZ91D *** lowest corrosion current density((5.73±2.75)×10^(−8)A·cm^(−2))was achieved,which was approximately three orders of magnitude less than that of bare ***,the coating demonstrated biocompatibility with no evident cytotoxicity,cellular damage,and hemolytic *** study provides an effective method for preparing coatings on Mg alloy surfaces with excellent corrosion resistance and biocompatibility.

关键词： Magnesium alloy Roughness Corrosion resistance Layered double hydroxides Biocompatibility

Success rate of current human-derived gastric cancer organoids establishment and influencing factors:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1626-1646页

作者： Kai-Lin Jiang Xiang-Xiang Wang Xue-Jiao Liu Li-Kun Guo Yong-Qi Chen Qing-Ling Jia Ke-Ming Yang Jiang-Hong Ling Department of gastroenterology Shuguang HospitalShanghai 200021China Department of pathology Shuguang HospitalShanghai 200021China

BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally *** To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using *** PubMed,Web of Science,and EMBASE were searched for *** trained researchers selected the studies and extracted *** 17.0 software was used for meta-analysis of the incidence of each outcome *** adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included *** plots and Egger’s test were used to detect publication *** analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging *** Eight studies with a pooled success rate of 66.6%were *** derived from women and men had success rates of 67%and 46.7%,*** from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,*** of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,*** with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,*** generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM *** Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.

关键词： Gastric cancer organoids Human-derived organoids Gastric cancer Cell lines In vitro research models