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Ethanol extract of Cyathulae Radix inhibits osteoclast differentiation and bone loss

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Chinese Journal of Natural Medicines 2024年第3期22卷 212-223页

作者： SHI Liying REN Liuyi LI Jinping LIU Xin LU jingjing jia Lujuan XIE Baoping TANg Siyuan LIU Wei ZHANg Jie Department of Pharmachemistry Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China Hunan Key laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases Central South UniversityChangsha 410013China Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of EducationGannan Medical UniversityGanzhou 341000China Xiangya Nursing School Central South UniversityChangsha 410013China The Third Xiangya Hospital Central South UniversityChangsha 410013China

Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning *** enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced *** its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain *** this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and ***-week-old female mice underwent ovariectomy and were treated with CEE for eight ***-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical ***-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPg)***-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB *** with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric *** E2 and OPg levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE *** downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein *** bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast *** with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regula

关键词： Osteoporosis Osteoclast BMMs Cyathulae Radix RANKL ER/RANK/NFATc1 signaling pathway

Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 135-146页

作者： Sujie Huang Yuxuan gao Ling Ma Bo jia Wenhao Zhao Yufan Yao Wenyuan Li Tongyi Lin Rui Wang jingjing Song Wei Zhang Institute of Pharmacology School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Key Laboratory of Preclinical Study for New Drugs of gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China State Key Laboratory of Veterinary Etiological Biology College of Veterinary MedicineLanzhou UniversityLanzhou 730000China Lanzhou University Second Hospital Lanzhou UniversityLanzhou 730000China

Melittin,a classical antimicrobial peptide,is a highly potent antitumor ***,its significant toxicity seriously hampers its application in tumor *** this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with *** conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic ***,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the ***-AAM-1 significantly suppressed melanoma growth in vivo with relatively low ***,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

关键词： Antimicrobial peptide Peptide-drug conjugate Cell-penetrating activity Membrane disruption Antitumor activity

Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

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World Journal of Emergency Medicine 2024年第3期15卷 229-231页

作者： Yi Yao Na Xu Xiaofang Tang Ce Zhang Sida jia jingjing Xu Ying Song Xueyan Zhao Runlin gao Jinqing Yuan Center for Coronary Heart Disease National Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional *** to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is *** contrast,big ET-1.

关键词： coronary percutaneous endothelin

Phosphatidylcholine protects against the hepatotoxicity of acrylamide via maintaining metabolic homeostasis of glutathione and glycerophospholipid

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Food Science and Human Wellness 2024年

作者： Yaoran Li Wei jia Yiju Zhang Yong Wu Li Zhu jingjing jiao Yu Zhang Department of gastroenterology the First Affiliated Hospital Zhejia.g University School of Medicine Zhejia.g Key Laboratory for Agro-Food Processing College of Biosystems Engineering and Food Science Zhejia.g University Department of gastroenterology the First Affiliated Hospital Zhejia.g University School of Medicine Zhejia.g Key Laboratory for Agro-Food Processing College of Biosystems Engineering and Food Science Zhejia.g University College of Food Science and Technology Yunnan Agricultural University College of Chemistry and Life Sciences Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources Chengdu Normal University Department of Nutrition School of Public Health Department of Clinical Nutrition of Affiliated Second Hospital Zhejia.g University School of Medicine

Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity. Phosphatidylcholine is thought to protect the liver from damage， but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear. We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches. Overall， 32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection. Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione， cysteine and L-ascorbic acid， and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation. The phosphatidylcholine treatment reduces the expression of cytochrome P450 2E1， alleviates the oxidative stress and inflammation of the liver， and stabilizes the content of glutathione， and thus alleviates the disorder of glutathione. Meanwhile， phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol， thereby maintaining metabolic homeostasis of glycerophospholipid. The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure， but not significantly change the levels of mercapturic acid adducts of acrylamide， providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.

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Nutritional and lipid profile status of children with spinal muscular atrophy in China:A retrospective case-control study

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Chinese Medical Journal 2024年第10期137卷 1243-1245页

作者： Yijie Feng jia Wei Mei Yao jianing Jin Yiqin Cui Qi Long Fei Chen Yi Hong Dongming Zhou jingjing Hu Xiao Chen Feng gao Changzheng Yuan Shanshan Mao Department of Neurology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Infection Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Nutrition Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China School of Public Health Zhejiang University School of MedicineHangzhouZhejiang 310012China Children’s Hospital School of Public HealthZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

To the Editor:5q spinal muscular atrophy(5qSMA)is an autosomal recessive neuromuscular disorder caused by the lack of the survival motor neuron(SMN)protein encoded by the SMN1 gene,located at 5q11.2-q13.3.[1]The incidence is 1/10,000-1/6000 live births,and the mutation carrier rate in China is 1/42.[1]Spinal muscular atrophy(SMA)is mainly divided into four subtypes:SMA type I,II,III,and IV,based on the motor milestones ever *** I-III occur in children,[1]which often result in progressive muscular atrophy and weakness as well as multi-system dysfunction,including nutritional and metabolic issues.[2]Children with SMA may have hidden nutritional and lipid imbalances,despite normal body appearance and anthropometric measurements,making it difcult to detect early and intervene.

关键词： atrophy muscular children

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical genetics and Hunan Key Laboratory of Medical genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

Multifunctional catalytic sites regulation of atomic-scale iridium on orthorhombic-CoSe_(2)for high efficiency dual-functional alkaline hydrogen evolution and organic degradation

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Journal of Energy Chemistry 2024年第5期92卷 271-281页

作者： jingjing Huang Chenglin Zhong Yanjie Xia jia Liu guizhen Li Chao Yang jiahong Wang Qian Wang Zhenbao Zhang Feng Yan jia.ghua Wu Yu Deng Zhenjia.g Zhou Xingchen He Paul K.Chu Woon-Ming Lau Xue-Feng Yu College of Chemistry and Chemical Engineering Linyi UniversityLinyi 276005ShandongChina Shenzhen Engineering Center for the Fabrication of Two-Dimensional Atomic Crystals Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055GuangdongChina National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional MaterialsCollege of Engineering and Applied Sciences and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093JiangsuChina College of Biosystems Engineering and Food Science Zhejiang UniversityHangzhou 310058ZhejiangChina Department of Physics Department of Materials Science and EngineeringDepartment of Biomedical EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina

The earth-abundant and high-performance catalysts are crucial for commercial implementation of hydrogen evolution reaction(HER).Herein,a multifunctional site strategy to construct excellent HER catalysts by incorporating iridium(Ir)ions on the atomic scale into orthorhombic-CoSe2(Ir-CoSe_(2))was *** hydrogen evolution activity in alkaline media such as a low overpotential of 48.7 mV at a current density of 10 mA cm^(-2)and better performance than commercial Pt/C catalysts at high current densities were found in the Ir-CoSe_(2) *** the experiments and theoretical calculations,it was revealed that Ir enabled CoSe_(2)to form multifunctional sites to synergistically catalyze alkaline HER by promoting the adsorption and dissociation of H_(2)O(Ir sites)and optimizing the binding energy for H^(*)on Co *** was noticeable that the electrolytic system comprising the Ir-CoSe_(2)electrode not only produced hydrogen efficiently via HER,but also degraded organic pollutants(Methylene blue).The cell voltage of the dual-function electrolytic system was 1.58 V at the benchmark current density of 50 mA cm^(-2),which was significantly lower than the conventional water splitting *** was indicated that this method was a novel strategy for designing advanced HER electrocatalysts by constructing multifunctional catalytic sites for hydrogen production and organic degradation.

关键词： Orthorhombic-CoSe_(2) Multifunctional sites design Hydrogen evolution reaction Synergistically catalyze Methylene blue oxidation

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin jia.g Juanjuan Ding Li Wang Xiaowen Wang jingjing Cui Shipin Feng Xiaojie gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li jia jiao Daoqi Wu gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(gWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a gWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPg was significant between SSNSWR and healthy controls,and that of two SNPs in gAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNPs were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in gAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in egFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the gWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

基于响应面法的轻质尾翼均匀挤压成形数值模拟及模具结构优化

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兵工学报 2024年第6期45卷 1824-1839页

作者：贾晶晶张治民于建民薛勇吴昂中北大学机电工程学院山西太原030051 郑州轻工业大学机电工程学院河南郑州450000 中北大学材料科学与工程学院山西太原030051

针对轻质镁合金尾翼正挤压成形金属流动不均匀和力学性能各向异性大的问题,提出一种可调控金属均匀流动的金属蓄料池模具结构。基于Deform-3D有限元模拟分析,采用Box-Behnken响应曲面法以金属蓄料池结构参数:深度h、池壁距尾翼芯部型腔... 详细信息

针对轻质镁合金尾翼正挤压成形金属流动不均匀和力学性能各向异性大的问题,提出一种可调控金属均匀流动的金属蓄料池模具结构。基于Deform-3D有限元模拟分析,采用Box-Behnken响应曲面法以金属蓄料池结构参数:深度h、池壁距尾翼芯部型腔长度D 1、池壁距翼片型腔长度D 2和池壁与翼片型腔之间夹角α为变量,建立出模口金属流速均方差和成形载荷与金属蓄料池结构参数之间的响应关系。响应曲面分析结果表明:最佳的金属蓄料池结构参数为h=7 mm,D 1=13 mm,D 2=6 mm,α=11°。采用优化后的模具结构参数进行模拟验证和物理试验,金属流动不均匀和力学性能各向异性均得到改善,并成功试制出形状尺寸和力学性能指标满足要求的尾翼形零件。

关键词：尾翼构件均匀流动有限元模拟模具优化 Box-Behnken响应曲面