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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang nan hu Yu-Wei Deng Long-Wei hu Hao Gu nan Luo Jin Wen Xin-Quan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis Spermine Rac1 Zebrafish Mice

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Single-cell transcriptomics systematically discloses the immune-inflammatory responses of peripheral blood mononuclear cells for diabetic nephropathy

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Genes & Diseases 2024年第4期11卷 82-85页

作者： Jiangpeng wu nan hu Baochun Guo hualin Ma Lulin Xie Yisha huang Siyu Xia Yuke Jiang Zhije Li Jigang Wang Xinzhou Zhang Zhen Liang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China Department of Geriatrics and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China

Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes mellitus.Although functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains limited.Here,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.

关键词： nephropathy alterations mortality

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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng nan hu Zhi-Hao Wang Chang-Cheng Tao Ya-Ru Wang Yue Liu Zulihumaer Aizimuaji Hong-Wei Wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Hernia Surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,

关键词： Telomerase Bibliometric analysis Telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

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Operando monitoring of dendrite formation in lithium metal batteries via ultrasensitive tilted fiber Bragg grating sensors

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Light(Science & Applications) 2024年第1期13卷 153-166页

作者： Xile Han Hai Zhong Kaiwei Li Xiaobin Xue Wen Wu nan hu Xihong Lu Jiaqiang huang Gaozhi Xiao Yaohua Mai Tuan Guo Institute of Photonics Technology Jinan UniversityGuangzhou 510632China Institute of New Energy Technology College of Information Science and TechnologyJinan UniversityGuangzhou 510632China Key Laboratory of Bionic Engineering(Ministry of Education) Jilin UniversityChangchun 130022China The Key Lab of Low-Carbon Chemistry&Energy Conservation of Guangdong Province School of ChemistrySun Yat-Sen UniversityGuangzhou 510275China Sustainable Energy and Environment Thrust The Hong Kong University of Science and Technology(Guangzhou)NanshaGuangzhouGuangdong 511400China Advanced Electronics and Photonics Research Centre National Research Council of CanadaOttawa K1A OR6Canada

Lithium(Li)dendrite growth significantly deteriorates the performance and shortens the operation life of lithium metal batteries.Capturing the intricate dynamics of surface localized and rapid mass transport at the electrolyte–electrode interface of lithium metal is essential for the understanding of the dendrite growth process,and the evaluation of the solutions mitigating the dendrite growth issue.Here we demonstrate an approach based on an ultrasensitive tilted fiber Bragg grating(TFBG)sensor which is inserted close to the electrode surface in a working lithium metal battery,without disturbing its operation.Thanks to the superfine optical resonances of the TFBG,in situ and rapid monitoring of mass transport kinetics and lithium dendrite growth at the nanoscale interface of lithium anodes have been achieved.Reliable correlations between the performance of different natural/artificial solid electrolyte interphases(SEIs)and the time-resolved optical responses have been observed and quantified,enabling us to link the nanoscale ion and SEI behavior with the macroscopic battery performance.This new operando tool will provide additional capabilities for parametrization of the batteries’electrochemistry and help identify the optimal interphases of lithium metal batteries to enhance battery performance and its safety.

关键词： battery lithium electrolyte

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： hu Qi Dan Tian Fei Luan Ruocong Yang nan Zeng State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Ramsey Numbers of Trees Versus Multiple Copies of Books

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 600-612页

作者： Xiao-bing GUO Si-nan hu Yue-jian PENG School of Mathematical Sciences Luoyang Normal UniversityLuoyang 471934China School of Mathematics Hunan UniversityChangsha 410082China

Given two graphs G and H,the Ramsey number R(G,H) is the minimum integer N such that any two-coloring of the edges of K_(N) in red or blue yields a red G or a blue H.Let v(G) be the number of vertices of G and χ(G) be the chromatic number of G.Let s(G) denote the chromatic surplus of G,the number of vertices in a minimum color class among all proper χ(G)-colorings of G.Burr showed that R(G,H)≥(v(G)-1)(χ(H)-1)+s(H) if G is connected and v(G)≥s(H).A connected graph G is H-good if R(G,H)=(v(G)-1)(χ(H)-1)+s(H).Let tH denote the disjoint union of t copies of graph H,and let G∨H denote the join of G and H.Denote a complete graph on n vertices by K_(n),and a tree on n vertices by T_(n).Denote a book with n pages by B_(n),i.e.,the join K_(2) ∨■.Erd?s,Faudree,Rousseau and Schelp proved that T_(n) is B_(m)-good if n≥3m-3.In this paper,we obtain the exact Ramsey number of T_(n) versus 2B_(2).Our result implies that T_(n) is 2B_(2)-good if n≥5.

关键词： ramsey number ramsey goodness tree book

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Cardiac energy metabolism disorder mediated by energy substrate imbalance and mitochondrial damage upon tebuconazole exposure

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Journal of Environmental Sciences 2024年第2期136卷 270-278页

作者： Tingting Ku Jindong hu Mengmeng Zhou Yuanyuan Xie Yutong Liu Xin Tan Lin Guo Guangke Li nan Sang College of Environmental Science and Resources Research Center of Environment and HealthShanxi UniversityTaiyuan 030006China

Tebuconazole exposure has been described as an increasing hazard to human health.An increasing number of recent studies have shown a positive association between tebuconazole exposure and cardiovascular disease risk,which is characterized by the reduction of adenosine triphosphate(ATP)synthesis.However,researches on the damage of tebuconazole exposure to energy metabolism and the related molecular mechanisms are limited.In the present study,male C57BL/6 mice were treated with tebuconazole at different low concentrations for 4 weeks.The results indicated that tebuconazole could accumulate in the heart and further induce the decrease of ATP content in the mouse heart.Importantly,tebuconazole induced an obvious shift in substrate utilization of fatty acid and glucose by disrupting their corresponding transporters(GLUT1,GLUT4,CD36,FABP3 and FATP1)expression,and significantly repressed the expression of mitochondrial biogenesis(Gabpa and Tfam)and oxidative phosphorylation(CS,Ndufa4,Sdhb,Cox5a and Atp5b)related genes in a dosedependent manner.Further investigation revealed that these alterations were related to the IRS1/AKT and PPARγ/RXRαpathways.These findings contribute to a better understanding of triazole fungicide-induced cardiovascular disease by revealing the key indicators associated with this phenomenon.

关键词： Tebuconazole Cardiotoxicity Energy metabolic disorders Energy substrate Mitochondrial damage

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Advances in the study of mitophagy in osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 197-211页

作者： Hong CAO Xuchang ZHOU Bowen XU Han hu Jianming GUO Miao WANG nan LI Jun ZOU Department of Sport Rehabilitation Shanghai University of SportShanghai 200438China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China School of Sport Medicine and Rehabilitation Beijing Sport UniversityBeijing 100084China

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of age.The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process.Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism.Therefore,maintaining mitochondrial homeostasis is an important strategy to mitigate OA.Mitophagy is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial homeostasis.Cumulative studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA.By reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

关键词： Mitophagy Osteoarthritis Chondrocyte Mitochondria Apoptosis

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Quantifying the agreement and accuracy characteristics of four satellite-based LULC products for cropland classification in China

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Journal of Integrative Agriculture 2024年第1期23卷 283-297页

作者： Jie Xue Xianglin Zhang Songchao Chen Bifeng hu nan Wang Zhou Shi Department of Land Management Zhejiang UniversityHangzhou 310058China Institute of Applied Remote Sensing and Information Technology College of Environmental and Resource SciencesZhejiang UniversityHangzhou 310058China ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311215China Department of Land Resource Management School of Public Finance and Public AdministrationJiangxi University of Finance and EconomicsNanchang 330013China Key Laboratory of Data Science in Finance and Economics Jiangxi University of Finance and EconomicsNanchang 330013China Key Laboratory of Spectroscopy Sensing Ministry of Agriculture and Rural AffairsHangzhou 310058China

Various land use and land cover(LULC)products have been produced over the past decade with the development of remote sensing technology.Despite the differences in LULC classification schemes,there is a lack of research on assessing the accuracy of their application to croplands in a unified framework.Thus,this study evaluated the spatial and area accuracies of cropland classification for four commonly used global LULC products(i.e.,MCD12Q1V6,GlobCover2009,FROM-GLC and GlobeLand30)based on the harmonised FAO criterion,and quantified the relationships between four factors(i.e.,slope,elevation,field size and crop system)and cropland classification agreement.The validation results indicated that MCD12Q1 and GlobeLand30 performed well in cropland classification regarding spatial consistency,with overall accuracies of 94.90 and 93.52%,respectively.The FROMGLC showed the worst performance,with an overall accuracy of 83.17%.Overlaying the cropland generated by the four global LULC products,we found the proportions of complete agreement and disagreement were 15.51 and 44.72% for the cropland classification,respectively.High consistency was mainly observed in the Northeast China Plain,the huang-huai-Hai Plain and the northern part of the Middle-lower Yangtze Plain,China.In contrast,low consistency was detected primarily on the eastern edge of the northern and semiarid region,the Yunnan-Guizhou Plateau and southern China.Field size was the most important factor for mapping cropland.For area accuracy,compared with China Statistical Yearbook data at the provincial scale,the accuracies of different products in descending order were:GlobeLand30,FROM-GLC,MCD12Q1,and GlobCover2009.The cropland classification schemes mainly caused large area deviations among the four products,and they also resulted in the different ranks of spatial accuracy and area accuracy among the four products.Our results can provide valuable suggestions for selecting cropland products at the national or provincial scale and help cropland mapping and reconstr

关键词： global LULC products cropland mapping accuracy evaluation food security China

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Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 212-232页

作者： Hong CAO Xuchang ZHOU Bowen XU Han hu Jianming GUO Yuwei MA Miao WANG nan LI Jun ZOU Department of Sport Rehabilitation Shanghai University of SportShanghai 200438China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

关键词： Endoplasmic reticulum-associated degradation(ERAD) Protein folding Ubiquitination Retrotranslocation

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