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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National translational science Center for Molecular Medicine & department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

Unveiling the culprit:the fusobacterium lineage that populates colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2349-2350页

作者： Johannes Betge Matthias P.Ebert department of Medicine Ⅱ Medical Faculty MannheimHeidelberg UniversityMannheimGermany Junior Clinical Cooperation Unit translational Gastrointestinal Oncology and preclinical Models German Cancer Research Center(DKFZ)HeidelbergGermany DKFZ Hector Cancer Institute at University Medical Center MannheimGermany MMPU Microbiota Drug Metabolism and Cancer Therapy European Molecular Biology LaboratoryHeidelbergGermany

In a recent study published in Nature,Zepeda-Rivera et al.1 discovered that one distinct clade of Fusobacterium nucleatum animalis(Fna)dominates the colorectal cancer(CRC)tumor *** work unravels a more precise understanding of a major bacterial species associated with CRC progression,thereby establishing a new focus for future studies,which may aid to develop improved microbiome-based diagnostics and treatments(Fig.1).

关键词： colorectal al. cancer

Alleviative effects of Bacillus coagulans strains on irritable bowel syndrome-unraveling strain specificity through physiological and genomic analysis

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Food science and Human Wellness 2024年第4期13卷 1845-1855页

作者： Jiang Cao Leilei Yu Jianxin Zhao Hao Zhang Wei Chen Yuzheng Xue 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 department of Gastroenterology Affiliated Hospital of Jiangnan UniversityWuxi 214122China

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different ***,6 *** strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of *** strains are *** results of this study showed that the ingestion of *** GBI-30,6086,and *** CCFM1041 significantly alleviated IBS symptoms in *** contrast,other *** strains showed no or limited alleviating effects on IBS *** to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary *** strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional *** *** results also suggest that administration of *** could significantly regulate microbiota dysbiosis in animal ***,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.

关键词： Baciillus coagulans Irritable bowel syndrome Resistance to bile salts Comparative genomic analysis Gut microbiota

D-band center coordination modulated enzyme-like activity in Fe-Cu dual-metal single-atom nanozymes

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Nano Research 2024年第7期17卷 5872-5883页

作者： Ling Liu Shaofang Zhang Guo Li Yadong Zhe Jiamin Liu Xinxu Zhang Jiahao Wei Xin Sun Yonghui Li Xiao-Dong Zhang Tianjin Key Laboratory of Brain science and Neural Engineering Academy of Medical Engineering and Translational MedicineTianjin UniversityTianjin 300072China department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology School of SciencesTianjin UniversityTianjin 300350China

After explorations in a diversity of single-atom nanozymes(SAzymes),developing dual-centered SAzymes becomes a promising approach for superior catalytic *** confusing mechanisms including atomic coordination,spatial configuration,and metal–metal atom interaction hinder the development and design of ***,a dual-centered Fe-Cu-N_(x)SAzyme exhibits excellent peroxidase(POD)-and catalase(CAT)-like activities with d-band center(ε_(d))coordination of Fe and Cu in multiple reaction stages,which plays a critical role in the adsorption of H_(2)O_(2)molecule and H_(2)O and O_(2)***,the dband center coordination,which can be represented byε_(d)(Fe)–ε_(d)(Cu)shifts,leads to the competition between one-side and bilateral adsorption,which determines the favorable reaction path with lower energy *** on experimental statistics,simulated formation energies,and reaction barriers,3 configurations,Fe-Cu-N6-I,Fe-Cu-N_(8)-II,and Fe-Cu-N_(8)-III,are modeled and ***,configuration-dependent catalytic selectivity and the competition between one-side and bilateral adsorption can be unveiled by d-band center coordination paradigm *** simulations suggest that the unsymmetrical charge distribution over the three Fe-Cu configurations could tune the adsorption strength compared with the counterparts FeN_(4)and CuN_(4).The present work provides a potential route for optimizing enzyme-like catalysis by designing the dual-or even triple-metal SAzymes,which demonstrates the large space to modulate the metal atomic configuration and interaction.

关键词： single-atom catalysis Fe-Cu dual-metal d-band center coordination enzyme mimicking competitive adsorption mechanisms

Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su Institute of translational Medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for translational Medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

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

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National translational science Center for Molecular Medicine and department of Cell Biology Fourth Military Medical UniversityXi'an 710000China department of Neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB