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Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping

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Journal of Pharmaceutical Analysis 2024年第3期14卷 335-347页

作者： Ding-Jun Hao Yue qin Shi-Jie Zhou Bu-Huai Dong Jun-Song Yang Peng Zou Li-Ping Wang yuan-Ting Zhao Department of Spine Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Anesthesiology Honghui HospitalXi'an Jiaotong UniversityXi'an710054China Department of Cardiovascular Medicine Honghui HospitalXi'an Jiaotong UniversityXi'an710054China State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy West China HospitalSichuan UniversityChengdu610041China

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is *** study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial ***-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,*** single-cell RNA sequencing data were retrieved for bioinformatic *** results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent *** a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by ***11 expression was unaffected by rhHapln1 ***,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and *** mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial *** addition,rmHapln1 induced hiPSC-CM *** conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling ***1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

关键词： Hapln1 Versican GDF11 iPSC-CMs Cardiomyocyte proliferation

Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo yuan qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

Multi-agent policy transfer via task relationship modeling

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Science China(Information Sciences) 2024年第8期67卷 102-114页

作者： Rongjun qin Feng CHEN Tonghan WANG Lei yuan Xiaoran WU Yipeng KANG Zongzhang ZHANG Chongjie ZHANG Yang YU National Key Laboratory for Novel Software Technology Nanjing University Polixir Technologies School of Engineering and Applied Sciences Harvard University Department of Computer Science and Technology Tsinghua University Institute for Interdisciplinary Information Sciences Tsinghua University

Team adaptation to new cooperative tasks is a hallmark of human intelligence, which has yet to be fully realized in learning agents. Previous studies on multi-agent transfer learning have accommodated teams of different sizes but heavily relied on the generalization ability of neural networks for adapting to unseen tasks. We posit that the relationship among tasks provides key information for policy *** utilize this relationship for efficient transfer by attempting to discover and exploit the knowledge among tasks from different teams, proposing to learn an effect-based task representation as a common latent space among tasks, and using it to build an alternatively fixed training scheme. Herein, we demonstrate that task representation can capture the relationship among teams and generalize to unseen tasks. Thus, the proposed method helps transfer the learned cooperation knowledge to new tasks after training on a few source ***, the learned transferred policies help solve tasks that are difficult to learn from scratch.

关键词： multi-agent reinforcement learning cooperative transfer learning task relationship modeling multi-agent policy reuse multi-agent multi-task learning

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Glycnsisitin A:A promising bicyclic peptide against heart failure that facilitates TFRCmediated uptake of iron in cardiomyocytes

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3125-3139页

作者： Jichao Zhou yuanyuan Liu Xiaoli Wei Meng yuan Xu Zhang Lingfeng qin Bing Cui Pingping Li Jing Zhang Ziming Feng Jianshuang Jiang Xiang yuan Ruibing Xu Zhimeng Zhang Peicheng Zhang Xiaowei Zhang Yanan Yang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in *** the monarch drug of Zhigancao decoction,the bioactive molecules of licorice against heart diseases remain *** established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides,glycnsisitins A-C(1-3),with distinctive C-C and C-O-C side-chain-toside-chain linkages from the roots of Glycyrrhiza uralensis(Licorice).Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin(DOX)-induced cardiomyocyte *** A treatment not only reduced the mortality of heart failure(HF)mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial *** set enrichment analysis(GSEA)of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the ***,glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor(TFRC),which caused increased uptake of iron in *** findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF,and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

关键词： Glycyrrhiza uralensis Bicyclic peptides Myocardial energy metabolism Iron homeostasis TFRC

Novel sandwich structured glass fiber Cloth/Poly(ethylene oxide)-MXene composite electrolyte

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Nano Materials Science 2024年第1期6卷 60-67页

作者： Yu-qin Mao Guang-He Dong Wei-Bin Zhu yuan-qing Li Pei Huang Shao-Yun Fu College of Aerospace Engineering Chongqing UniversityChongqing400044China State Key Laboratory of Power Transmission Equipment and System Security and New Technology Chongqing UniversityChongqing400044China

Recently,poly(ethylene oxide)(PEO)-based solid polymer electrolytes have been attracting great attention,and efforts are currently underway to develop PEO-based composite electrolytes for next generation high performance all-solid-state lithium metal *** this article,a novel sandwich structured solid-state PEO composite electrolyte is developed for high performance all-solid-state lithium metal *** PEO-based composite electrolyte is fabricated by hot-pressing PEO,LiTFSI and Ti_(3)C_(2)T_(x) MXene nanosheets into glass fiber cloth(GFC).The as-prepared GFC@PEO-MXene electrolyte shows high mechanical properties,good electrochemical stability,and high lithium-ion migration number,which indicates an obvious synergistic effect from the microscale GFC and the nanoscale *** as,the GFC@PEO-1 wt%MXene electrolyte shows a high tensile strength of 43.43 MPa and an impressive Young's modulus of 496 MPa,which are increased by 1205%and 6048%over those of ***,the ionic conductivity of GFC@PEO-1 wt%MXene at 60℃ reaches 5.01×10^(-2) S m^(-1),which is increased by around 200%compared with that of GFC@PEO *** addition,the Li/Li symmetric battery based on GFC@PEO-1 wt%MXene electrolyte shows an excellent cycling stability over 800 h(0.3 mA cm^(-2),0.3 mAh cm^(-2)),which is obviously longer than that based on PEO and GFC@PEO electrolytes due to the better compatibility of GFC@PEO-1 wt%MXene electrolyte with Li ***,the solid-state Li/LiFePO_(4) battery with GFC@PEO-1 wt%MXene as electrolyte demonstrates a high capacity of 110.2–166.1 mAh g^(-1) in a wide temperature range of 25–60C,and an excellent capacity retention *** developed sandwich structured GFC@PEO-1 wt%MXene electrolyte with the excellent overall performance is promising for next generation high performance all-solid-state lithium metal batteries.

关键词： Solid polymer electrolyte Ti_(3)C_(2)T_(x)MXene Poly(ethylene oxide) Glass fiber cloth All-solid-state Li metal Battery

Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1871-1882页

作者： Long Li Dong-yuan Liu Jing Leng Xue-Mei Tao Hui-qin Wu Yan-Peng Zhu Department of General Surgery The 971^(st)Hospital of Chinese People's Liberation ArmyQingdao 266071Shandong ProvinceChina Department of Surgery Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina Hyperbaric Oxygen Department The Eighth Peoples Hospital of QingdaoQingdao 266121Shandong ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China

BACKGROUND The development of laparoscopic technology has provided a new choice for surgery of gastric cancer(GC),but the advantages and disadvantages of laparoscopic total gastrectomy(LTG)and laparoscopic-assisted total gastrectomy(LATG)in treatment effect and safety are still *** purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC,and to provide a basis for clinical *** To compare the efficacy of totally LTG(TLTG)and LATG in the context of radical gastrectomy for ***,we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy *** Literature on comparative studies of the above two surgical methods for GC(TLTG group and LATG group)published before September 2022 were searched in the PubMed,Web of Science,Wanfang Database,CNKI,and other Chinese and English *** addition,the following search keywords were used:Gastric cancer,total gastrectomy,total laparoscopy,laparoscopy-assisted,esophagojejunal anastomosis,gastric/stomach cancer,total gastrectomy,totally/completely laparoscopic,laparoscopic assisted/laparoscopy assisted/laparoscopically assisted,and esophagojejunostomy/esophagojejunal *** Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature,extracted the data,and evaluated the risk of bias in the included *** After layer-by-layer screening,258 pieces of literature were recovered,and 11 of those pieces were eventually *** resulted in a sample size of 2421 instances,with 1115 cases falling into the TLTG group and 1306 cases into the LATG *** or sex differences between the two groups were not statistically significant,according to the meta-analysis,however the average body mass index of the TLTG group was considerably higher than that of the LATG group(P=0.01).Compared with those in the LATG group,the incision length in the TLTG

关键词： Total laparoscopic gastrectomy Laparoscopically assisted total gastrectomy Gastric cancer Meta-analysis

lmpact of non-canonical ALK fusion on the efficacy of targeted therapy in non-small cell lung cancer

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Chinese Medical Journal 2024年第12期137卷 1468-1470页

作者： Hao Zeng Qi Wei yuan Tang yuanyuan Zhang Sihan Tan qin Huang Xin Pu Yalun Li Panwen Tian Department of Pulmonary and Critical Care Medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pulmonary and Critical Care Medicine Lung Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Pulmonary and Critical Care Medicine State Key Laboratory of Respiratory Health and MultimorbidityPrecision Medicine Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:With the wide application of next-generation sequencing(NGS),a number of EML4-ALK fusion partners or coexisting(non)-EML4-ALK and non-EML4-ALK have been detected in non-small cell lung cancer(NSCLC).Although targeted therapies for patients with metastatic NSCLC and actionable mutations dramatically change how these patients are treated,studies have demonstrated differences in progression-free survival(PFS)among patients based on different ALK fusion partners.

关键词： targeted lung NSCLC

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian qin Yuxin Jin Yiming qin Feifei yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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Asian Journal of Andrology 2024年第1期26卷 57-66页

作者： Chang-Bo Zhao Wei-Bo Chen Wen-Zhen Wang Fang-Xin Gong Cui-qin Fan Ye Li Tian Lan Wen-Jing Wang Ming-Zhen yuan Department of Urology Shandong Provincial HospitalShandong UniversityJinan 250012China Department of Andrology Liaocheng People's HospitalShandong UniversityLiaocheng 252000China Department of Urology The Second Hospital of Shandong UniversityJinan 250012China Department of Physiology School of Basic Medical SciencesShandong UniversityJinan 250012China

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging *** factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this ***,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of *** results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control ***,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile *** expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED *** expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED ***,the cell morphology in the cavernous tissue of the DMED group also changed ***,-OA treatment significantly reversed all these changes observed in the DMED *** conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

关键词： apoptosis diabetic mellitus erectile dysfunction nitro-oleic acid NO/cGMP pathway oxidative stress