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An improved installation of 2-hydroxy-4-methoxybenzyl(iHmb)method for chemical protein synthesis

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Chinese Chemical Letters 2024年第5期35卷 145-150页

作者： Ying Li long-jie Wang Yong-Kang Zhou Jun Liang Bin Xiao ji-Shen Zheng The First Affiliated Hospital of USTC MOE Key Laboratory for Membraneless Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China department of Chemistry University of Science and Technology of ChinaHefei 230027China

The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated sidereactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus improving the synthesis of long and challenging peptides and ***,its use is largely precluded by the limited Hmb’s installation *** this report,an improved installation of Hmb(iHmb)method was developed to achieve the flexible installation and the convenient removal of *** iHmb method involves two critical steps:(1)oxidative diazotization of the readily installed 2-hydroxy-4-methoxy-5-amino-benzyl(Hmab)to give 2-hydroxy-4-methoxy-5-diazonium-benzyl(Hmdab)by combining soamyl nitrite(IAN)/HBF_(4),and(2)reductive elimination of Hmdab to give the desired Hmb by 1,2-ethanedithiol(EDT).The iHmb method enables the installation of Hmb at any primary amino acid including the highly sterically hindered amino acids(e.g.,valine and isoleucine).The practicality and utility of the iHmb method was demonstrated by one-shot solid-phase synthesis of a challenging aspartimide-prone peptide,the mirror-image version of a hydrophobic peptide and a long-chain peptide up to ***,the iHmb method can be utilized to facilitate chemical protein ligation,as exemplified by the synthesis of the single-spanning membrane protein *** iHmb method expands the toolkit for peptide synthesis and ligation and facilitates the preparation of peptides/proteins.

关键词： Chemical protein synthesis Solid-phase peptide synthesis Removable backbone modification 2-Hydroxy-4-methoxybenzyl(Hmb)group Aspartimide-prone peptides Difficult peptides Membrane proteins

Possible Role of cellular Polyamine Metabolism in Neuronal Apoptosis

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Current Medical Science 2024年第2期44卷 281-290页

作者： Xin-tong ji Wen-lei YU Meng-jia jiN Lin-jie LU hong-ping YIN Huan-huan WANG School of Basic Medical Sciences Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou 311121China School of Medicine Chongqing UniversityChongqing 400030China department of Stomatology Huzhou Wuxing District People's HospitalHuzhou Wuxing District Maternal and Child Health HospitalHuzhou 313008China School of Pharmacy Zhejiang UniversityHangzhou 310030China department of Stomatology Haining Hospital of Traditional Chinese MedicineJiaxing 314400China

Recent studies have shown that cellular levels of polyamines(PAs)are significantly altered in neurodegenerative *** from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress,mitochondrial metabolism,cellular immunity,and ion channel *** of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative ***,in the current work,evidence was collected to determine the possible associations between cellular levels of PAs,and related enzymes and the development of several neurodegenerative diseases,which could provide a new idea for the treatment of neurodegenerative diseases in the future.

关键词： polyamine apoptosis mitochondria neurodegenerative disease

Tissue-resident macrophages exacerbate lung injury after remote sterile damage

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cellular & Molecular Immunology 2024年第4期21卷 332-348页

作者： Hanhui Zhong jingjing ji jinling Zhuang Ziying Xiong Pengyun Xie Xiaolei Liu Jundi Zheng Wangli Tian Xiaoyang hong jing Tang The department of Anesthesiology Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdongChina The department of Critical Care Medicine General Hospital of Southern Theater Command of PLAGuangzhouChina The department of Respiratory Medicine Guangdong Provincial Hospital of Integrated Chinese and Western MedicineFoshanChina Pediatric Intensive Care Unit Senior Department of Pediatricsthe Seventh Medical Center of PLA General HospitalBeijingChina

Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to ***,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory *** found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or *** findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating *** study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung ***,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.

关键词： tissue-resident macrophage RAGE remote sterile damage

Decoding topological XYZ^(2) codes with reinforcement learning based on attention mechanisms

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Chinese Physics B 2024年第6期33卷 262-270页

作者：陈庆辉姬宇欣王柯涵马鸿洋纪乃华 School of Information and Control Engineering Qingdao University of TechnologyQingdao 266033China School of Sciences Qingdao University of TechnologyQingdao 266033China

Quantum error correction, a technique that relies on the principle of redundancy to encode logical information into additional qubits to better protect the system from noise, is necessary to design a viable quantum computer. For this new topological stabilizer code-XYZ^(2) code defined on the cellular lattice, it is implemented on a hexagonal lattice of qubits and it encodes the logical qubits with the help of stabilizer measurements of weight six and weight two. However topological stabilizer codes in cellular lattice quantum systems suffer from the detrimental effects of noise due to interaction with the environment. Several decoding approaches have been proposed to address this problem. Here, we propose the use of a state-attention based reinforcement learning decoder to decode XYZ^(2) codes, which enables the decoder to more accurately focus on the information related to the current decoding position, and the error correction accuracy of our reinforcement learning decoder model under the optimisation conditions can reach 83.27% under the depolarizing noise model, and we have measured thresholds of 0.18856 and 0.19043 for XYZ^(2) codes at code spacing of 3–7 and 7–11, respectively. our study provides directions and ideas for applications of decoding schemes combining reinforcement learning attention mechanisms to other topological quantum error-correcting codes.

关键词： quantum error correction topological quantum stabilizer code reinforcement learning attention mechanism

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu ji-Chuan Liu Zi-Ling Shi Quan-hong Ma department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

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Chinese Journal of Integrative Medicine 2024年第4期30卷 348-358页

作者： FU Yu-bing LIU Chen-feng WANG jin-jia ji Xiao-lin TANG Rong-han LIAO Kun-yu CHEN Ling-yue hong Ya-zhen FAN Bin-bin WANG Shi-cong LIU Wen-Hsien State Key Laboratory of cellular Stress biology School of Life SciencesFaculty of Medicine and Life ScienceXiamen UniversityXiamenFujian Province(361102)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development ZhangzhouFujian Province(363000)China

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma *** Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of *** growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 *** cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH *** PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P1).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P1).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P1 or P1 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

关键词： Pien Tze Huang metastasis anti-tumor immunity T cell activation T cell exhaustion immune checkpoints Chinese medicine

Epithelial Sodium and Chloride Channels and Asthma

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Chinese Medical Journal 2015年第16期128卷 2242-2249页

作者： Wen Wang, hong-long ji department of Respiratory and Critical Care Medicine Beijing Chaoyang Hospital Capital Medical University Beijing Institute of Respiratory Medicine Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders Beijing 100020 China department of cellular and Molecular biology Texas Lung Injury Institute University of Texas Health Science Center at Tyler Tyler Texas 75708 USA

Objective：To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel （ENaC）/chlorine ion *** Sources：The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google *** terms used in the literature search were：（1） ENaCs;cystic fibrosis （CF） transmembrane conductance regulator （CFTR）;asthma/asthmatic,（2） ENaC/sodium salt;CF;asthma/asthmatic,（3） CFTR/chlorine ion channels;asthma/asthmatic,（4） ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and （5） CFTR;CF;asthma/asthmatic （ti）.Study Selection：These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years （from 1990 to 2015）.The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the ***：Airway surface liquid dehydration can cause airway inflammation and *** and CFTR are closely related to the airway mucociliary *** transporters may play a critical role in pathogenesis of asthmatic ***：Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.

关键词： Airway Surface Liquid Asthma Cystic Fibrosis Transmembrane Conductance Regulator Epithelial Sodium Channel Mucociliary Clearance

MRE11 lactylation:a linker between Warburg effect and DNA repair

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Life Metabolism 2024年第3期3卷 6-8页

作者： Pingyu Liu hongbin ji Fuming Li Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Institute of Metabolism and Integrative biology State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China university of Chinese Academy of Sciences Beijing 100049China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China School of Life Science and Technology Shanghai Tech UniversityShanghai 200120China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China

Lysine lactylation is a recently discovered post-translational modification with emerging roles in both physiology and disease.A recent study published in Cell shows that lactate-induced lactylation of the homologous recombination(HR)protein meiotic recombination 11 results in HR hyperactivation and chemoresistance in cancer cells,establishing a previously unrecognized link between cellular metabolism and deoxyribonucleic acid(DNA)damage repair and providing new insights into how altered glucose metabolism can impact DNA damage response in cancer.

关键词： metabolism damage establishing