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

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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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5

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Frontiers of Medicine 2024年第1期18卷 81-97页

作者： Liwei Sun xueting Yang Amjad Khan xue yu Han Zhang Shirui Han Xiaerbati Habulieti Yang Sun Rongrong Wang xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory for Complex Severe and Rare DiseasesInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing100005China Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineNational Key Clinical Speciality Construction Project(Obstetrics and Gynecology)Chongqing Health Center for Women and ChildrenChongqing400013China Chongqing Clinical Research Center for Reproductive Medicine Women and Children’s Hospital of Chongqing Medical UniversityChongqing400013China Faculty of Biological Sciences Department of ZoologyUniversity of Lakki MarwatKhyber Pakhtunkhwa28420Pakistan Institute for Medical Genetics and Applied Genomics University of TübingenTübingen72076Germany Alexander von Humboldt fellowship Foundation Berlin10117Germany Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Department of Laboratory Medicine State Key Laboratory for Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

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Estimation of surface geometry on combustion characteristics of AP/HTPB propellant under rapid depressurization

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Defence Technology（防务技术） 2024年第3期33卷 546-558页

作者： Kaixuan Chen Zhenwei Ye Xiaochun xue Yonggang yu School of Energy and Power Engineering Nanjing University of Science and TechnologyNanjing 210094JiangsuChina School of Science Hangzhou Dianzi UniversityHangzhou 310018ZhejiangChina

The 2D sandwich model serves as a potent tool in exploring the influence of surface geometry on the combustion attributes of Ammonium perchlorate/Hydroxyl-terminated polybutadiene(AP/HTPB)propellant under rapid pressure decay.The thickness of the sandwich propellant is derived from slicing the 3D random particle packing,an approach that enables a more effective examination of the micro-flame structure.Comparative analysis of the predicted burning characteristics has been performed with experimental studies.The findings demonstrate a reasonable agreement,thereby validating the precision and soundness of the model.Based on the typical rapid depressurization environment of solid rocket motor(initial combustion pressure is 3 MPa and the maximum depressurization rate is 1000 MPa/s).A-type(a flatter surface),B-type(AP recesses from the combustion surface),and C-type(AP protrudes from the combustion surface)propellant combustion processes are numerically simulated.Upon comparison of the evolution of gas-phase flame between 0.1 and 1 ms,it is discerned that the flame strength and form created by the three sandwich models differ significantly at the beginning stage of depressurization,with the flame structures gradually becoming harmonized over time.Conclusions are drawn by comparison extinction times:the surface geometry plays a pivotal role in the combustion process,with AP protrusion favoring combustion the most.

关键词： AP/HTPB propellant BDP model Rapid pressure decay Burning surface geometry

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Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 577-582页

作者： Qiu-yu Jiang Ru-Yi xue Department of Gastroenterology and Hepatology Zhongshan HospitalShanghai Institute of Liver DiseaseFudan UniversityShanghai 200032China Department of Gastroenterology and Hepatology Shanghai Baoshan District Wusong Central Hospital(Zhongshan Hospital Wusong BranchFudan University)Shanghai 200940China

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

关键词： Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio Immunecheckpoint inhibitor Immune-related adverse event

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Carbon dots-derived three-dimensional-ordered macroporous host with high penetrability and catalytic activity for LSBs under lean electrolyte

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Rare Metals 2024年第6期43卷 2560-2573页

作者： Jiao-Zi Duan Hua-yu Pei Quan Yang xue Li Xin Ba xue Yong Jun-Ling Guo Si-yu Lu Green Catalysis Center College of ChemistryZhengzhou University Country State Center for International Cooperation On Designer Low-Carbon & Environmental Materials School of Materials Science and EngineeringZhengzhou University Hubei Institute of Quality Supervision Inspection Department of Chemistry University of Sheffield

The practical energy density of lithium-sulfur batteries（LSBs） is seriously limited by the high electrolyte-to-sulfur ratios（E/S）.The E/S can be reduced by employing hosts with easy-to-infiltrate structure that ensures the uniform distribution of a lean electrolyte and high catalytic activity that can suppress "shuttle effect" via accelerating the slow conversion of soluble poly sulfides to insoluble sulfides.Among the easy-to-infiltrate structures,the three-dimensional-ordered macroporous（3DOM）structure is easier to scale preparation and more suitable for the existing industrial processes.However,it is difficult to obtain the 3DOM with（1） high penetrability due to the high viscosity of frequently-used organic polymer precursors and（2） high catalytic activity due to the low confinement effect,meaning that uniformly dispersed small-sized catalytic materials are difficult to load on 3DOM.Herein,using carbon dots（CDs） with both organic and inorganic properties as a precursor and aggregation limiting agent,a 3DOM host with high penetrability and homodispersed Ni particles of small sizes（Ni-CDs-3DOM）was synthesized.In this host:（1） CDs precursor with suitable viscosity can improve the penetrability.（2） CDs can effectively inhibit the agglomeration of Ni particles.（3） Uniformly dispersed small-size Ni particles offer high-efficiency catalytic activity toward sulfur reactions.Consequently,the Ni-CDs-3DOM/sulfur cathode exhibits high sulfur utilization and stable cycling performance even under high sulfur loading(5.5 mg·cm-1) and low E/S(6.5 μl·mg-1).This work indicates the usefulness of CDs in constructing hosts for LSBs with high energy density.

关键词： Lithium–sulfur batteries Carbon dots Catalytic action Easy-to-infiltrate structure Lean electrolyte

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Relationships between Terrain Features and Forecasting Errors of Surface Wind Speeds in a Mesoscale Numerical Weather Prediction Model

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Advances in Atmospheric Sciences 2024年第6期41卷 1161-1170页

作者： Wenbo xue Hui yu Shengming TANG Wei HUANG Chinese Academy of Meteorological Sciences Beijing 100081China University of Chinese Academy of Sciences Beijing 101408China Shanghai Typhoon Institute/CMA Shanghai 200030China Key Laboratory of Numerical Modeling for Tropical Cyclone/CMA Shanghai 200030China

Numerical weather prediction(NWP)models have always presented large forecasting errors of surface wind speeds over regions with complex terrain.In this study,surface wind forecasts from an operational NWP model,the SMS-WARR(Shanghai Meteorological Service-WRF ADAS Rapid Refresh System),are analyzed to quantitatively reveal the relationships between the forecasted surface wind speed errors and terrain features,with the intent of providing clues to better apply the NWP model to complex terrain regions.The terrain features are described by three parameters:the standard deviation of the model grid-scale orography,terrain height error of the model,and slope angle.The results show that the forecast bias has a unimodal distribution with a change in the standard deviation of orography.The minimum ME(the mean value of bias)is 1.2 m s^(-1) when the standard deviation is between 60 and 70 m.A positive correlation exists between bias and terrain height error,with the ME increasing by 10%−30%for every 200 m increase in terrain height error.The ME decreases by 65.6%when slope angle increases from(0.5°−1.5°)to larger than 3.5°for uphill winds but increases by 35.4%when the absolute value of slope angle increases from(0.5°−1.5°)to(2.5°−3.5°)for downhill winds.Several sensitivity experiments are carried out with a model output statistical(MOS)calibration model for surface wind speeds and ME(RMSE)has been reduced by 90%(30%)by introducing terrain parameters,demonstrating the value of this study.

关键词： surface wind speed terrain features error analysis MOS calibration model

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Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

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Food Science and Human Wellness 2024年第1期13卷 472-481页

作者： Wenjun xue Wenzhu Zhao Sijia Wu Zhipeng yu School of Food Science and Engineering Hainan UniversityHaikou 570228China College of Food Science and Engineering Bohai UniversityJinzhou 121013China Lab of Nutrition and Functional Food Jilin UniversityChangchun 130062China

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

关键词： ACE inhibitory peptide Kidney Mechanism Metabolomics Spontaneously hypertensive rats

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Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

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World Journal of Gastroenterology 2024年第21期30卷 2751-2762页

作者： yu Liang Zhen Meng xue-Li Ding Man Jiang Department of Pharmacy The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina Department of Intervention The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

关键词： Drug safety Proton pump inhibitor Inflammatory bowel disease Ulcerative colitis Crohn’s disease

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Phase separation of S-RNase promotes self-incompatibility in Petunia hybrida

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Journal of Integrative Plant Biology 2024年第5期66卷 986-1006页

作者： Huayang Tian Hongkui Zhang Huaqiu Huang yu'e Zhang Yongbiao xue The State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental Biologythe Chinese Academy of SciencesBeijing 100101China University of the Chinese Academy of Sciences Beijing 100049China Beiing Institute of Genomics Chinese Academy of SciencesNational Center for BioinformationBeijing 100101China

Self-incompatibility(SI)is an intraspecific reproductive barrier widely present in angiosperms.The SI system with the broadest occurrence in angiosperms is based on an S-RNase linked to a cluster of multiple S-locus F-box(SLF)genes found in the Solanaceae,Plantaginaceae,Rosaceae,and Rutaceae.Recent studies reveal that non-self S-RNase is degraded by the Skip Cullin F-box(SCF)SLF-mediated ubiquitin–proteasome system in a collaborative manner in Petunia,but how self-RNase functions largely remains mysterious.Here,we show that S-RNases form S-RNase condensates(SRCs)in the self-pollen tube cytoplasm through phase separation and the disruption of SRC formation breaks SI in self-incompatible Petunia hybrida.We further find that the pistil SI factors of a small asparagine-rich protein HT-B and thioredoxin h together with a reduced state of the pollen tube all promote the expansion of SRCs,which then sequester several actin-binding proteins,including the actin polymerization factor PhABRACL,the actin polymerization activity of which is reduced by S-RNase in vitro.Meanwhile,we find that S-RNase variants lacking condensation ability fail to recruit PhABRACL and are unable to induce actin foci formation required for pollen tube growth inhibition.Taken together,our results demonstrate that phase separation of S-RNase promotes SI response in P.hybrida,revealing a new mode of S-RNase action.

关键词： self-incompatibility S-RNase phase separation

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Optical scattering imaging with sub-nanometer precision based on position-ultra-sensitive giant Lamb shift

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 96-105页

作者： Zeyang Liao yu-Wei Lu Wei Li xue-Hua Wang State Key Laboratory of Optoelectronic Materials and Technologies School of PhysicsSun Yat-sen UniversityGuangzhou 510275China Quantum Science Center of Guangdong-Hong Kong-Macao Greater Bay Area(Guangdong) Shenzhen 518045China

The Lamb shift of a quantum emitter in close proximity to a plasmonic nanostructure can be three or more orders of magnitude larger than that in the free space and is ultra-sensitive to the emitter position and polarization.We demonstrate that this large Lamb shift can be sensitively observed from the scattering or absorption spectrum dip shift of the coupled system when the plasmonic nanoparticle or tip scans the emitter.Using these observations,we propose a scanning optical scattering imaging method based on the plasmonic-enhanced Lamb shift with achieves sub-nanometer resolution.Our method is based on the scattering or absorption spectrum of the plasmon-emitter coupling system,which is free of the fluorescence quenching problem and easier to implement in a plasmon-emitter coupling system.In addition,our scheme works even if the quantum emitter is slightly below the dielectric surface,which can bring about broader applications,such as detecting atoms and molecules or quantum dots above or under a surface.

关键词： Lamb shift plasmon optical scattering imaging

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