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Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of Oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina department of Oral and Maxillofacial Surgery Zhongshan HospitalFudan UniversityShanghaiChina School and hospital of Stomatology Kunming Medical UniversityKunmingChina center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue Cancer center of Peking university Third hospital Beijing 100191China center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Peking university Third hospital Cancer center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed *** ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism *** a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian ***,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related *** 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the *** data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian *** of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian ***,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian *** findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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The Reduced Accuracy of Non-invasive Tests for Significant Fibrosis in Chronic Hepatitis B Patients with metabolic Dysfunction-associated Steatotic Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 827-829页

作者： Fajuan Rui Wenjing Ni Yee Hui Yeo Youwen Tan Liang Xu Junping Shi Jie Li department of Infectious diseases Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingJiangsuChina department of Infectious Disease Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina Karsh Division of Gastroenterology and Hepatology Cedars-Sinai Medical CenterLos AngelesCAUSA The Third hospital of Zhenjiang Affiliated Jiangsu university School of MedicineJiangsu UniversityZhenjiangJiangsuChina Clinical School of the Second People’s hospital Tianjin Medical UniversityTianjinChina department of Hepatology Tianjin Second People’s HospitalTianjinChina Tianjin Research Institute of Liver diseases TianjinChina department of Infectious diseases The Affiliated Hospital of Hangzhou Normal UniversityHangzhouZhejiangChina

metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD),is increasingly prevalent in Asia,1 an area also endemic for chronic hepatitis B(CHB).Our previous study showed that the coexistence of CHB and hepatic steatosis(HS)has reached 36.5%in Asia,2 with a similar figure observed globally.3 This coexistence may exacerbate the progression of hepatic fibrosis.

关键词： metabolic hepatic NAFLD

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Exercise-induced microbial changes in preventing type 2 diabetes

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut *** we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and *** found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students *** additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance ***,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation *** propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

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The alarming link between neonicotinoid insecticides and kidney injury

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Emerging Contaminants 2024年第3期10卷 318-328页

作者： Zhanpeng Zhang Longbin Shen Mei Chen Biao Huang Zhuoqi Wei Weiguo Xu Hua Zhang department of metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou510632China department of Dermatology The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong510632China department of Rehabilitation Medicine The First Affiliated Hospital of Jinan UniversityGuangzhou510632China department of Interventional The First Affiliated Hospital of Guangzhou University of Traditional Chinese MedicineGuangzhou510400China Zhuhai Interventional Medical center Zhuhai Precision Medical CenterZhuhai People's HospitalZhuhai Hospital Affiliated with Jinan UniversityZhuhaiGuangdong519000China

Neonicotinoid insecticides(NEOs)have been extensively approved for application in agricultural production both in China and *** studies indicated that human exposure to NEOs would have adverse health ***,studies on occurrences of NEOs in kidney injury patients and their association with nephrotoxicity are *** study investigates the potential correlation between exposure to NEOs and kidney injury within a subset(n=224)of the population residing in South *** of 8 NEOs and 5 metabolites were quantified in blood samples obtained from both the 110 healthy and 114 kidney injury cohorts in South *** found that target analytes were frequently detected in samples from the healthy and kidney injury cohorts(61%-100%).Dinotefuran is the predominant NEO in the healthy(42.3%)and kidney injury cohort(49.6%).Significantly positive(p<0.05)associations between blood NEO concentrations and kidney injury were found,indicating that these pollutants may increase the odds of human kidney injury *** multilinear regression analysis,it was observed that the concentrations of various NEOs exhibited a significant association(p<0.05)with hematological parameters linked to *** study represents the pioneering investigation examining the relationships between NEOs and kidney injury,thereby offering novel insights into the nephrotoxicity associated with these *** discovery carries significant implications for public health policies and environmental conservation practices.

关键词： Neonicotinoid insecticides Metabolites Human exposure Kidney injury

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Unveiling the oral-gut connection:chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE^(−/−)Mice on a high-fat diet

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International Journal of Oral Science 2024年第3期16卷 515-527页

作者： Guowu Gan Shihan Lin Yufang Luo Yu Zeng Beibei Lu Ren Zhang Shuai Chen Huaxiang Lei Zhiyu Cai Xiaojing Huang Fujian Key Laboratory of Oral diseases&Fujian Provincial Engineering Research center of Oral Biomaterial&Stomatology Key Laboratory of Fujian College and university School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Institute of Stomatology&Research center of Dental and Craniofacial Implants School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Stomatology Fujian Medical University Union HospitalFuzhouChina

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE^(−/−)mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species *** profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis ***,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was *** increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular *** conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD *** findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

关键词： atherosclerosis metabolism impaired

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Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

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Current Medical Science 2024年第1期44卷 121-133页

作者： Ting-ting WEI Wen XU Bo TU Wan-xue ZHANG Xin-xin YANG Yiguo ZHOU Shan-shan ZHANG Jun-lian YANG Ming-zhu XIE Juan DU Wei-wei CHEN Qing-bin LU department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China department of Infectious Disease The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China department of Laboratorial Science and Technology&Vaccine Research center School of Public HealthPeking UniversityBeijing 100191China department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China Global center for Infectious Disease and Policy Research&Global Health and Infectious diseases Group Peking UniversityBeijing 100191China Key Laboratory of Epidemiology of Major diseases(Peking university) Ministry of EducationBeijing 100191China

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains *** the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were *** In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had *** samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted *** Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and *** metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid *** sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI *** and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

关键词： human adenovirus metabonomic lipids pneumonia upper respiratory tract infection

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Th17/Treg balance and macrophage polarization ratio in lower extremity arteriosclerosis obliterans

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 127-136,I0006-I0009页

作者： Zhen-Zhen Li Min Liu Xiong-Hui He Zhen-Dong Liu Zhan-Xiang Xiao Hao Qian You-Fei Qi Cun-Chuan Wang department of metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong Province510632China department of Vascular Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouHainan Province570311China department of Physical Examination Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouHainan Province570311China department of Gastrointestinal Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouHainan Province570311China

Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were *** was used to detect interleukin 6(IL-6),IL-10,and ***-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 ***,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ***:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ***,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control *** Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO *** endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.

关键词： Lower extremity arteriosclerosis Regulatory T cells Regulatory B cells Inflammatory factors M1 macrophages M2 macrophages

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The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

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Science China(Life Sciences) 2024年第8期67卷 1549-1562页

作者： Peidong Zhang Peiwei Li Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOEState Key Laboratory of BiotherapyWest China Second HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Physician Scientist Training Program Department of MedicineWashington University School of MedicineSt.Louis 63110USA department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China department of Radiation Oncology Taussig Cancer CenterCleveland ClinicCleveland 44106USA

Mechanics shape cell and tissue plasticity and maintain their *** cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic ***,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains ***,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)*** the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway *** subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical *** further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic ***,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

关键词： pan-cancer cancer mechanics multi-omics immunology

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Biological Profile and Cardiovascular Risk in Patients Receiving Neuroleptics at the Psychiatric department of the university hospital center of brazzaville

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Journal of Biosciences and Medicines 2024年第6期12卷 33-42页

作者： Landry Martial Miguel Paul Gandou Justecidi Kiang Choupette Ravelle Dobhat-Doukakini Didier Gesril Njilo Tchatchouang Childerick Lekana Destin Mbemba Bahamboula Archange Emmanuel Mboungou Malonga Donatien Moukassa Alain Maxime Mouanga Ange Antoine Abena Biochemical and Pharmacology Laboratory Faculty of Health Sciences Marien Ngouabi University Brazzaville Republic of Congo Psychiatric department University Hospital Center Brazzaville Republic of Congo department of Biological Sciences Dnis Sassou-NGuesso University Kintl Republic of Congo

Several studies report the problem of cardiovascular tolerance of treatments with neuroleptics, given the important number of morbidities in patients with mental illnesses. This preliminary work aimed to describe the epidemiological and biological profile of patients taking neuroleptics and followed in the psychiatry department of brazzaville university hospital, from the angle of cardiovascular risk. Fifty (50) patients (17 men and 33 women), with a mean age of 33.9 10.7 years, were included. Epidemiological data (sex, age, tobacco or alcohol consumption) were collected on pre-established survey forms. Biochemical (total cholesterol, HDL-c, triglycerides and atherogenicity index) and inflammatory parameters (ultra-sensitive CRP, troponin I and NT-ProBNP) were investigated using enzymatic and indirect immunofluorescence technical, respectively. The results obtained showed that 54% of patients were obese, 94% were non-smokers, and 12% had high blood pressure. 10% of patients had high total cholesterol levels and 90% had HDL cholesterol levels below 60 mg/dl. Triglycerides and atherogenicity index were significantly elevated in relation to Body Mass Index (BMI). Ultrasensitive CRP was elevated in 38% of patients. In conclusion, this study revealed an association between lipid parameters (triglycerides and atherogenicity index) in relation to BMI in patients taking neuroleptics followed in the Psychiatry department of university hospital center of brazzaville.

关键词： Neuroleptic Cardiovascular Risk Psychiatry brazzaville

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