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Demonstration of safety characteristics and effects on gut microbiota of Lactobacillus gasseri HMV18

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Food Science and Human Wellness 2024年第2期13卷 611-620页

作者： Xianxian Jia Miaomiao Jia Xiang Gao Xiang Li Mengyuan Wang Shengqiang Du Rui Huang Xiaotong Li Jun Zhang Shujin Li Chunling Ma Yan Zhang Bin Cong Department of Pathogen biology Institute of basic MedicineHebei Medical UniversityShijiazhuang 050017China Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology Chinese Academy of Medical SciencesShijiazhuang 050017China institute of Basic medicine Hebei Medical UniversityShijiazhuang 050017China College of Forensic medicine Hebei Key Laboratory of Forensic MedicineCollaborative Innovation Center of Forensic Medical Molecular IdentificationHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety Key Laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050227China

Human normal flora is a source of *** safety characteristics of a specific isolate determine its application in foods or *** food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human *** this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether *** HMV18 can colonize in the gut or modulate the gut microbiota after oral *** results suggest that *** HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's *** HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for *** to cause infection is relatively ***,this work provides a basis for the foods or drugs application of *** HMV18 and gives a map of experiments for the safety assessment of probiotics.

关键词： Probiotics Lactobacillus gasseri Safety assessment Gut microbiota

Metabolic plasticity of T cell fate decision

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Chinese Medical Journal 2024年第7期137卷 762-775页

作者： Xiaoli Pan Jiajia Wang Lianjun Zhang Guideng Li Bo Huang National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Key Laboratory of Synthetic biology Regulatory Element Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhouJiangsu 215123China Department of Immunology&National Key Laboratory of Medical Molecular biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China Department of Biochemistry&Molecular biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei 430030China

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T *** antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory ***,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted *** studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell *** this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory ***,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted *** the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

关键词： T cell immunotherapy T cell differentiation T cell exhaustion Metabolic reprogramming Tumor microenvironment

Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all *** physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic *** few or too many blood vessels are associated with the onset and progression of many *** response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases

Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João B.Relvas institute of Research and Innovation in Health(i3S)and institute for Molecular and Cell biology(IBMC) University of PortoPortoPortugal Department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun Cancer institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Highly efficient discovery of the covalent Minhibitors from crude Pu-erh tea by integrating biochemical and chemoproteomic approaches

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Food Science and Human Wellness 2024年

作者： Guang-Hao Zhu Ya-Ni Zhang Sheng-Lan Qi Jian-Rong Xu Yuan Xiong Zhao-Qin Zhang Xi-Xiang Chen Yuan-Yuan Xie Xiao-Qing Guan Wei-Dong Zhang Wei Liu Guang-Bo Ge Shanghai Frontiers Science Center of TCM Chemical biology institute of Interdisciplinary Integrative medicine Research Shanghai University of Traditional Chinese medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese medicine

The main proteases (Mpros) are hydrolases playing essential roles in the replication of β-coronaviruses including SARS-CoV-2. Herein， a highly efficient strategy was developed for discovering the Mproinactivators from crude plant extract integrating target-based biochemical assay and chemoproteomic approaches. Firstly， Pu-erh tea was found to potently suppress SARS-CoV-2 Mproin a time-dependent manner. Next， global chemical analysis coupling with peptide-modification profiling were used to identify the cysteine-modified constituents in Pu-erh tea. The results suggested that seven constituents in Pu-erh tea could modify SARS-CoV-2 Mpro， which turned out that epigallocatechin， gallocatechin and gallic acid were the most efficacious Mproinactivators. Further investigations demonstrated that epigallocatechin and gallocatechin could inactivate SARS-CoV-2 Mprovia blocking the formation of the homodimers. Collectively， this work proposed a novel and practical strategy for highly efficient discovery of time-dependent inhibitors of SARS-CoV-2 Mprofrom plant extracts， while three constituents in Pu-erh tea have emerged as robust SARS-CoV-2 Mproinactivators.

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CRISPR-based genetic screens advance cancer immunology

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Science China Life Sciences 2024年

作者： Yuanfang Cao Xueting Li Yumu Pan Huahe Wang Siyu Yang Lingjuan Hong Lupeng Ye institute of Modern biology Nanjing University

CRISPR technologies have revolutionized research areas ranging from fundamental science to translational medicine. CRISPR-based genetic screens offer a powerful platform for unbiased screening in various fields, such as cancer immunology. Immune checkpoint blockade(ICB)therapy has been shown to strongly affect cancer treatment. However, the currently available ICBs are limited and do not work in all cancer patients. Pooled CRISPR screens enable the identification of previously unknown immune regulators that can regulate T-cell activation,cytotoxicity, persistence, infiltration into tumors, cytokine secretion, memory formation, T-cell metabolism, and CD4+T-cell *** novel targets can be developed as new immunotherapies or used with the current ICBs as new combination therapies that may yield synergistic efficacy. Here, we review the progress made in the development of CRISPR technologies, particularly technological advances in CRISPR screens and their application in novel target identification for immunotherapy.

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo Laboratory of Vascular biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and *** increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical *** central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this *** are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph *** the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including ***,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity Vascular endothelial growth factor C Immune modulation

Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

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Chinese Journal of Chemistry 2024年第5期42卷 533-542页

作者： Dong Wei Guo-Qiang Lin State Key Laboratory of Systems medicine for Cancer Shanghai Cancer InstituteShanghai Key Laboratory of Systems Regulation and Clinical Translation for CancerRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai200127 China State Key Laboratory of Chemical biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032 China

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic *** mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late *** reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization *** showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical *** Scientists In 1980,a seminal work by Breslow et *** an acceleration of reaction rate in the Diels-Alder *** and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic *** term "on-water" was then coined to describe this *** strategy was further expanded to transition-metal catalyzed transformations by Ackermann in ***,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou *** on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst *** recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck *** mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

关键词： Pd-catalyzed “On-water” Green chemistry Aqueous reactions Mechanism Methodology and reactions Mizoroki-Heck reaction Cross-coupling