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P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice

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Current Medical Science 2023年第6期43卷 1084-1095页

作者： Jing yu Yang ZHAO Xiao-kang GONG Zheng LIANG Yan-na ZHAO Xin LI yu-ju chen You-hua YANG Meng-juan WU Xiao-chuan WANG Xi-ji SHU Jian BAO Institute of Biomedical Sciences School of MedicineJianghan UniversityWuhan430056China Department of Pathology and Pathophysiology School of MedicineJianghan UniversityWuhan430056China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.

关键词： cyclin-dependent kinase 5 p25 post-stroke cognitive impairment tau hyperphosphorylation

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Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO ju-ying chenG Chien-shan CAO Zhang-qi chen Lian-yu chen Zhen Department of Integrative Oncology Fudan University Shanghai Cancer CenterShanghai(200032)China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome animal model pancreatic tumor evaluation methods

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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

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Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe chen Kai Wang Jie ju Xue yu Wanpeng yu Cuiyun Liu Yin Wang Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China College of Medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and repair.The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ultimately,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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Durable Ru Nanocrystal with HfO_(2)Modification for Acidic Overall Water Splitting

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Nano-Micro Letters 2024年第9期16卷 462-477页

作者： Xiangkai Kong Jie Xu Zhicheng ju Changle chen School of Materials and Physics China University of Mining and TechnologyXuzhou 221116JiangsuPeople’s Republic of China Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation Huaibei Normal UniversityHuaibei 235000AnhuiPeople’s Republic of China School of Chemistry and Materials Science University of Science and Technology of ChinaHefei 230026AnhuiPeople’s Republic of China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023JiangsuPeople’s Republic of China

Durable and efficient bi-functional catalyst,that is capable of both oxygen evolution reaction and hydrogen evolution reaction under acidic condition,are highly desired for the commercialization of proton exchange membrane water electrolysis.Herein,we report a robust L-Ru/HfO_(2)heterostructure constructed via confining crystalline Ru nanodomains by HfO_(2)matrix.When assembled with a proton exchange membrane,the bi-functional L-Ru/HfO_(2)catalyst-based electrolyzer presents a voltage of 1.57 and 1.67 V to reach 100 and 300 mA cm^(-2)current density,prevailing most of previously reported Ru-based materials as well as commercial Pt/C||RuO_(2)electrolyzer.It is revealed that the synergistic effect of HfO_(2)modification and small crystalline domain formation significantly alleviates the over-oxidation of Ru.More importantly,this synergistic effect facilitates a dual-site oxide path during the oxygen evolution procedure via optimization of the binding configurations of oxygenated adsorbates.As a result,the Ru active sites maintain the metallic state along with reduced energy barrier for the rate-determining step(*O→*OOH).Both of water adsorption and dissociation(Volmer step)are strengthened,while a moderate hydrogen binding is achieved to accelerate the hydrogen desorption procedure(Tafel step).Consequently,the activity and stability of acidic overall water splitting are simultaneously enhanced.

关键词： Ruthenium Hafnium dioxide Oxygen evolution catalysis Anti-oxidation

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On convergence of covariance matrix of empirical Bayes hyper-parameter estimator

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Control Theory and Technology 2024年第2期22卷 149-162页

作者： yue ju Biqiang Mu Tianshi chen School of Data Science and Shenzhen Research Institute of Big Data The Chinese University of Hong KongShenzhenShenzhen518172GuangdongChina Division of Decision and Control Systems School of Electrical Engineering and Computer ScienceKTH Royal Institute of Technology10044StockholmSweden Key Laboratory of Systems and Control Institute of Systems ScienceAcademy of Mathematics and System ScienceChinese Academy of SciencesBeijing100190China

Regularized system identification has become the research frontier of system identification in the past decade.One related core subject is to study the convergence properties of various hyper-parameter estimators as the sample size goes to infinity.In this paper,we consider one commonly used hyper-parameter estimator,the empirical Bayes(EB).Its convergence in distribution has been studied,and the explicit expression of the covariance matrix of its limiting distribution has been given.However,what we are truly interested in are factors contained in the covariance matrix of the EB hyper-parameter estimator,and then,the convergence of its covariance matrix to that of its limiting distribution is required.In general,the convergence in distribution of a sequence of random variables does not necessarily guarantee the convergence of its covariance matrix.Thus,the derivation of such convergence is a necessary complement to our theoretical analysis about factors that influence the convergence properties of the EB hyper-parameter estimator.In this paper,we consider the regularized finite impulse response(FIR)model estimation with deterministic inputs,and show that the covariance matrix of the EB hyper-parameter estimator converges to that of its limiting distribution.Moreover,we run numerical simulations to demonstrate the efficacy of ourtheoretical results.

关键词： Regularized system identification Hyper-parameter estimator Empirical Bayes Convergence of covariance matrix

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Atomically Dispersed Ruthenium Catalysts with Open Hollow Structure for Lithium-Oxygen Batteries

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Nano-Micro Letters 2024年第2期16卷 154-164页

作者： Xin chen yu Zhang Chang chen Huinan Li yuran Lin Ke yu Caiyun Nan chen chen Beijing Advanced Innovation Center for Materials Genome Engineering Institute of Solid State ChemistryUniversity of Science and Technology BeijingBeijing 100083People’s Republic of China Engineering Research Center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084People’s Republic of China Beijing Key Laboratory of Energy Conversion and Storage Materials Institution College of ChemistryBeijing Normal UniversityBeijing 100875People’s Republic of China

Lithium–oxygen battery with ultrahigh theoretical energy density is considered a highly competitive next-generation energy storage device,but its practical application is severely hindered by issues such as difficult decomposition of discharge products at present.Here,we have developed N-doped carbon anchored atomically dispersed Ru sites cathode catalyst with open hollow structure(h-RuNC)for Lithium–oxygen battery.On one hand,the abundance of atomically dispersed Ru sites can effectively catalyze the formation and decomposition of discharge products,thereby greatly enhancing the redox kinetics.On the other hand,the open hollow structure not only enhances the mass activity of atomically dispersed Ru sites but also improves the diffusion efficiency of catalytic molecules.Therefore,the excellent activity from atomically dispersed Ru sites and the enhanced diffusion from open hollow structure respectively improve the redox kinetics and cycling stability,ultimately achieving a high-performance lithium–oxygen battery.

关键词： Atomically dispersed Open hollow structure Discharge product Lithium Oxygen battery

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Pharmacological Effects of Botanical Drugs on Myocardial Metabolism in Chronic Heart Failure

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Chinese Journal of Integrative Medicine 2024年第5期30卷 458-467页

作者： HU yu-xuan QIU Sheng-lei SHANG ju-ju WANG Zi LAI Xiao-lei Beijing Hospital of Traditional Chinese Medicine Capital Medical UniversityBeijing 100010China

Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure.However,most of the drugs that increase cardiac energy are still in the theoretical or testing stage.Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism.In this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related targets.At the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.

关键词： botanical drugs chronic heart failure myocardial metabolism pharmacological effects review

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A smart hybrid memory scheduling approach using neural models

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Science China(Information Sciences) 2024年第4期67卷 333-334页

作者： Yanjie ZHEN Huijun ZHANG Yongheng DENG Weining chen Wei GAO ju REN yu chen Department of Computer Science and Technology Tsinghua University China Huaneng Clean Energy Research Institute

Traditional dynamic random access memory is limited by its low capacity and high cost because of the increasing demand for the memory capacity of applications. Hybrid memory architectures, including new memory hardwar... 详细信息

关键词： Cost reduction

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Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers

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Genes & Diseases 2024年第2期11卷 597-613页

作者： yu Zhang Xinliang Gu Yang Li yuejiao Huang Shaoqing ju Medical School of Nantong University Nantong UniversityNantongJiangsu 226001China Department of Laboratory Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Department of Medical Oncology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China

With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucleases on tRNAs,tsRNAs can be divided into two categories,tRNA halves(tiRNAs)and tRNA-derived fragments(tRFs),each with specific subcellular localizations.Additionally,the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications.In this review,we first elaborated on the classification and biogenesis of tsRNAs.After summarizing the latest mechanisms of tsRNAs,including transcriptional gene silencing,post-transcriptional gene silencing,nascent RNA silencing,translation regulation,rRNA regulation,and reverse transcription regulation,we explored the representative biological functions of tsRNAs in tumors.Furthermore,this review summarized the clinical value of tsRNAs in cancers,thus providing theoretical support for their potential as novel biomarkers and therapeutic targets.

关键词： Biogenesis Biological function Cancer Mechanism Therapeutic strategy tsRNAs

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Cronkhite-Canada syndrome with esophagus involvement and sixyear follow-up:A case report

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World Journal of Gastroenterology 2024年第8期30卷 984-990页

作者： yu-chen Tang Department of Endocrinology The First Affiliated Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare,noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities.CCS polyps are distributed through the whole digestive tract,and they are common in the stomach and colon but very uncommon in the esophagus.CASE SUMMARY Here,we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea,alopecia,and loss of his fingernails.Laboratory data indicated anemia,hypoalbuminemia,hypocalcemia,hypokalemia,and positive fecal occult blood.Endoscopy showed numerous polyps scattered throughout the digestive tract,including the esophagus.He was treated with nutritional support and glucocorticoids with remission of his symptoms.CONCLUSION Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms.Treatment should be individualized for each patient according to their therapy response.Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

关键词： Cronkhite-Canada syndrome Gastrointestinal polyposis Hormonal therapy Prognosis Case report

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