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Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren Tan Mary C.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh Tuck Wah Soong Jason K.W.Lee Ivan C.C.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore human potential translational research programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Centre for translational Magnetic Resonance research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance Centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore Campus for research Excellence and Technological Enterprise(CREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity Cognition Heat stress Hyperthermia Motor function

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Retinal Vascular Imaging Application in Women’s Reproductive Health:Clinical Implications and Future Directions

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Maternal-Fetal Medicine 2024年第2期6卷 92-96页

作者： Beth Shi Yu Lim Ling-Jun Li Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of Obstetrics&Gynaecology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore Global Centre for Asian Women’s Health Human Potential Translational Research ProgrammeYong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore NUS Bia-Echo Asia Centre for Reproductive Longevity and Equality(ACRLE) Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117456Singapore Singapore Eye research Institute Singapore National Eye CentreSingapore 168751Singapore

Over the past two decades,population-based studies employing semiautomatic computer-assisted programs have uncovered associations between retinal microvascular features and various systemic *** the recognition of retinal imaging in cardiometabolic health grows,there is increasing evidence supporting its application in women’s health,particularly during the reproductive *** review aims to summarize the indications of retinal imaging in women’s health and intergenerational health,where suboptimal retinal imaging has been found to mirror pathological systemic changes,such as suboptimal hemodynamic circulation,inflammation,endothelial dysfunction,oxidative stress,and hypoxia in *** from Singapore Growing Up in Singapore Towards Healthy Outcomes and Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohorts have reported serial changes in retinal conventional microvascular features(e.g.,retinal arteriolar narrowing,retinal venular widening)and retinal geometric microvascular features(e.g.,sparse fractal dimension,enlarged branching angle,and increased curvature tortuosity)during the preconception and antenatal *** morphological abnormalities were found to be related to female fertility,maternal antenatal health conditions,postnatal maternal cardiometabolic health,and intergenerational health in the *** the compelling evidence of the ability to detect microvascular changes through noninvasive methods at an early stage,retinal imaging holds the potential to facilitate timely interventions,mitigate the progression of complications,and prevent adverse pregnancy *** ahead,the convergence of artificial intelligence and advanced imaging techniques heralds a promising era in women’s health research and clinical practice.

关键词： Retinal vascular imaging Reproductive health

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Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

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Food Science and human Wellness 2024年第3期13卷 1201-1211页

作者： Dingwu Qu Zhennan Gu Saisai Feng Leilei Yu Fengwei Tian Hao Zhang Wei Chen Qixiao Zhai State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China National Engineering research Center for Functional Food Jiangnan UniversityWuxi 214122China Wuxi translational Medicine research Center and Jiangsu translational Medicine research Institute Wuxi Branch Wuxi 214122China

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome *** commensals have shown different functions in IBD prevention and *** gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut ***-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture *** showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal *** probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not ***,*** JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated ***,*** FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial ***,we provided insight into the clinical application of probiotics in IBD treatment.

关键词： Gut commensals Dextran sulfate sodium(DSS)colitis Intestinal barrier Immunoregulation

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Cell reprogramming therapy for Parkinson’s disease

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Neural Regeneration research 2024年第11期19卷 2444-2455页

作者： Wenjing Dong Shuyi Liu Shangang Li Zhengbo Wang State Key Laboratory of Primate Biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan ProvinceChina Yunnan Key Laboratory of Primate Biomedical research KunmingYunnan ProvinceChina

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars *** studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s *** initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical ***,ethical issues and tumor formation were limitations of its clinical *** pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell *** widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor *** induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s ***,there are also ethical concerns and the risk of tumor formation that need to be *** review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical *** review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo *** findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

关键词： animal models astrocytes autologous cell reprogramming cell therapy direct lineage reprogramming dopaminergic neurons induced pluripotent stem cells non-human primates Parkinson’s disease

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Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology ***,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical ***,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus ***,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in *** cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed *** also found expression of signaling pathways components that may increase the potential for chimera *** for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in *** engineered cells retained embryonic and extra-embryonic developmental ***,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living *** study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

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Exploiting neonatal host–bifidobacteria interactions to promote intestinal pathogen tolerance and barrier function: Bifidobacteriumlongum subsp. infantis outperforms Bifidobacteriumadolescentis in anti-Salmonella activity and maintenance of intestinal hom

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Food Science and human Wellness 2024年

作者： Chunxiu Lin Shunhe Wang Min Guo Wentian Li Jiayin Qiu Yonghua Zhou Hao Zhang Wei Chen Gang Wang Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology Jiangsu Institute of Parasitic Diseases State Key Laboratory of Food Science andResources Jiangnan University Wuxi translational Medicine research Center and Jiangsu translational Medicine research Institute Wuxi Branch (Yangzhou) Institute of Food Biotechnology Jiangnan University National Engineering research Center for Functional Food Jiangnan University School of Food Science and Technology Jiangnan University

Bifidobacteriumlongumsubsp. infantis (***. infantis) and Bifidobacteriumadolescentis(B. adolescentis) play important roles in the guts of infants and adolescents， respectively. In this study， using a neonatal rat model， we compared the protective effects of these two bifidobacterial species against Salmonella infection. The results demonstrated that ***. infantis was more effective than B. adolescentis in alleviating the severity of infection in newborn rats exposed to Salmonella entericaserovarTyphimurium strain SL1344. B. *** attenuated intestinal inflammation and mucosal damage induced by Salmonella infection， as well as protecting intestinal nerves and intestinal barrier function through TLR4/MyD88 signalling. B. longumsubsp. infantis also displayed the potential to modulate gut metabolites by promoting the biosynthesis of unsaturated fatty acids (arachidonic acid， eicosapentaenoic acid and α-linolenic acid) and purine metabolism (guanine， adenine， inosine and adenosine)， thereby regulating metabolic disturbances. Additionally， the benefits of B. *** were also observed in the liver， spleen and brain， improving nerve reflexes and suppressing hepatosplenomegaly. Overall， these findings provide novel insights into the prevention and treatment of gut-related diseases in newborns， highlighting the potentially significant role of B. *** in clinical applications.

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Krill oil attenuates obesity-induced skeletal muscle atrophy in mice

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Food Science and human Wellness 2024年

作者： Mengqing Zhou Yuhong Yang Yan Zheng Zijian Wu Chen Chen Qijian Liang Yu Yang Hao Wu Xin Guo Lei Du School of Food Science and Engineering Qilu University of Technology (Shandong Academy of Sciences) School of Public Health Cheeloo College of Medicine Shandong University research Center of translational Medicine Jinan Central Hospital Shandong University

Obesity is associated with skeletal muscle mass loss and physical dysfunction. Krill oil (KO) has been shown to be beneficial in human health. However， the effect of KO on obesity-induced skeletal muscle atrophy is still unclear. In this study， the male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity， and then were intragastric administration with 400 mg/kg bw KO for an additional 6 weeks. The results showed that KO treatment reduced body weight， fat accumulation and serum pro-inflammatory cytokines in HFD-induced obese mice. Importantly， KO treatment attenuated skeletal muscle atrophy in HFD-fed mice， as evidenced by preserving skeletal muscle mass， average myofiber cross-sectional area and grip strength. KO administration also mitigated obesity-induced ectopic lipid deposition and inflammatory response in skeletal muscle. Additionally， KO treatment inhibited the transcriptional activities of nuclear factor-kappa B (NF-κB) p65 and forkhead box O 3a (FoxO3a)， and then down-regulated muscle atrophy F-box (MAFbx) and muscle-specific RING finger protein 1 (MuRF1) protein levels in skeletal muscle from HFD-fed mice. KO administration also improved obesity-induced impaired muscle protein synthesis via activating PI3K/Akt pathway. Furthermore， KO treatment enhanced muscle mitochondrial biogenesis in HFD-induced obese mice via activating PGC-1α pathway. Collectively， KO might be developed as a potential nutritional supplement for the prevention and treatment of obesity-induced skeletal muscle atrophy.

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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

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Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

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Chinese Herbal Medicines 2024年第1期16卷 106-112页

作者： Mingyue Xiao Ronghua Luo Qinghua Liang Honglv Jiang Yanli Liu Guoqiang Xu Hongwei Gao Yongtang Zheng Qiongming Xu Shilin Yang College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and human Disease Mechanisms of Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Jiangsu Key Laboratory of Neuropsychiatric Diseases and Jiangsu Key Laboratory of Preventive and translational Medicine for Geriatric Diseases Soochow UniversitySuzhou 215123China College of Pharmacy Guangxi University of Chinese MedicineNanning 530000China

Objective: Anemoside B4(AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in ***: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8(CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore,label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type Ⅰ IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical ***: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein(N), Spike protein(S), and 3C-like protease(3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon(IFN)-β response via the activation of retinoic acid-inducible gene Ⅰ(RIG-1) like receptor(RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA ***: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

关键词： anemoside B4 interferon RNA metabolism quantitative proteomics SARS-CoV-2

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Interleukin-1β:Friend or foe for gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1676-1682页

作者： Kullanat Khawkhiaw Jutatip Panaampon Thanit Imemkamon Charupong Saengboonmee Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Center for translational Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Cholangiocarcinoma research Institute Khon Kaen UniversityKhon Kaen 40002Thailand Department of Medical Oncology Dana-Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215United States Department of Medicine Harvard Medical SchoolBostonMA 02215United States Division of Hematopoiesis Joint Research Center for Human Retrovirus InfectionKumamoto UniversityKumamoto 860-0811Japan Department of Medicine Faculty of MedicineKhon Kaen UnivsersityKhon Kaen 40002Thailand

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and ***-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related ***-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting *** studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in *** application of IL-1β inhibitors is also promising for targeted therapy development in some cancer ***,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different *** editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling *** and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

关键词： Cancer Gastrointestinal tract Inflammation Interleukin-1β Tumor microenvironment

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