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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

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Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI yan-hong LIAO Department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney ***,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal ***,the regulatory impact of TRPC6 on renal fibrosis remains *** In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham *** and serum were collected on days 7,14,21,and 28 after *** vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 *** anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western *** Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ***6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in ***,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 *** These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β*** TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1173-1189页

作者： yan Lin Jiangnan Wu Yong Zhuo Bin Feng Zhengfeng Fang Shengyu Xu Jian Li hua Zhao De Wu Lun hua Lianqiang Che Key Laboratory of Animal Disease‑Resistance Nutrition Animal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130SichuanChina

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high *** present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR *** Forty multiparous sows were allocated to the control or MET diet groups from mating until *** farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling *** The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of ***,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn *** also increased lactase and sucrase activity in the jejunum of newborn *** addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn *** methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn ***-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell *** contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic *** Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

关键词： Ileum Intrauterine growth restriction Methyl donor Methylation Sows

Regioselective C-C bond cleavage/aminocarbonylation cascade under copper catalysis

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Science China Chemistry 2024年第11期67卷 3798-3806页

作者： Qi-Chao Shan yan Zhao Yong Wu Hong-Fei Liu Xin-hua Duan Li-Na Guo Department of Chemistry School of Chemistry Energy Research Center of Energy Storage Materials and Devices Ministry of EducationXi'an Jiaotong University State Key Laboratory of Applied Organic Chemistry Lanzhou University

A regioselective C-C bond cleavage/aminocarbonylation cascade is presented. In recent years, tremendous progress has been made in the alkoxyl radical-mediated C-C bond cleavage of unstrained monocarbocycles. In contrast, the deconstruction and functionalization of bicyclic skeletons has been less developed and has mainly focused on the ring expansion process. Inspired by the aromatization-driven C-C bond cleavage, here we demonstrate a ring-opening/aminocarbonylation cascade under copper catalysis, in which the formation of a stable γ-lactam or succinimide skeleton reverses the selectivity of C-C cleavage. Remarkably, the photo and thermal assistance is not required when the succinimide skeleton is formed during the ring opening process. DFT calculations revealed that this unexpected ring-opening process is thermodynamically and kinetically favourable.

关键词： C-C bond cleavage controllable regioselectivity aminocarbonylation bicyclic alkoxy radical

Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao yan Xinghua Guo Minchuan Zhou yan Bai Jincan He hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong Engineering Research Center of Natural Products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

Influence of different magnetic forces on the effect of colonic anastomosis in rats

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 860-870页

作者： Bo-yan Tian Miao-Miao Zhang Jia Ma yi Lyu Xiao-Peng yan Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina Department of Surgical Oncology Shaanxi Provincial People's HospitalXi'an 710068Shaanxi ProvinceChina

BACKGROUND Despite much work having been conducted on magnetic compression anastomo-sis(MCA)in the digestive tract,there are no reports on the influence of magnetic force on the *** To investigate the effect of different magnetic force magnets on the MCA of the digestive *** Two groups of magnets of the same sizes but different magnetic forces were designed and produced.A total of 24 Sprague-Dawley rats were randomly assigned into two groups(powerful magnet group and common magnet group),with 12 rats in each *** types of magnets were used to complete the colonic side-to-side anastomosis of the *** operation time and magnet discharge time were *** anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured,and the anastomosis was observed via the naked eye and subjected to histological *** The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N,*** colonic side-to-side anastomosis was completed in all 24 rats,and the operation success rate and postoperative survival rate were 100%.No significant difference was noted in the operation time between the two *** magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group,but the difference was not statistically significant(P=0.513).Furthermore,there was no statistical difference in the burst pressure(P=0.266)or diameter of magnetic anastomosis(P=0.095)between the two *** gross specimens of the two groups showed good anastomotic healing,and histological observation indicated good mucosal continuity without differences on *** In the rat colonic side-to-side MCA model,both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.

关键词： Magnetosurgery Magnetic compression anastomosis Colonic anastomosis Magnetic force Rats

Spatial construction of ultrasmall Pt-decorated 3D spinel oxidemodified N-doped graphene nanoarchitectures as high-efficiency methanol oxidation electrocatalysts

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Rare Metals 2024年第1期43卷 186-197页

作者： Qi Zhang Min-Min yan Wen-Fa Du Chen-Yu yin Jian Zhang Lu yang Yun-Qing Kang Hai-yan He hua-Jie huang College of Mechanics and Materials Hohai UniversityNanjing 210098China New Energy Technology Engineering Lab of Jiangsu Province College of ScienceNanjing University of Posts&Telecommunications(NUPT)Nanjing 210023China International Center for Materials Nanoarchitectonics(WPIMANA) National Institute for Materials ScienceTsukuba 305-0044IbarakiJapan

Direct methanol fuel cell technology recently becomes the focus of both academic and engineering circles,which stimulates the exploitation and utilization of advanced electrode catalysts with high activity and long ***,we demonstrate a robust bottom-up approach to the spatial construction of three-dimensional(3D) spinel manganese-cobalt oxide-modified N-doped graphene nanoarchitectures decorated with ultrasmall Pt nanoparticles(Pt/MnCo_(2)O_(4)-NG) via a controllable selfassembly *** incorporation of MnCo_(2)O_(4)nanocrystals provides abundant hydroxyl sources to promote the oxidative removal of CO-like byproducts on Pt sites,while the existence of 3D porous N-doped graphene networks facilitates the transportation of both ions and electrons in the hybrid system,thus giving rise to remarkable synergetic coupling effects during the methanol oxidation ***,the optimized Pt/MnCo_(2)O_(4)-NG nano architecture expres ses exceptional electrocatalytic properties with a large electrochemically active surface area of 99.5 m^(2)·g^(-1),a high mass activity of1508.3 mA·mg^(-1),strong toxicity resistance and reliable long-term durability,which have obvious competitive advantages over those of conventional Pt/carbon black,Pt/carbon nano tube,Pt/graphene,and Pt/N-doped graphene catalysts with the same Pt usage.

关键词： Platinum MnCo_(2)O_(4) 3D graphene Electrocatalysts Methanol oxidation

The principle and amelioration of lithium plating in fast-charging lithium-ion batteries

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Journal of Energy Chemistry 2024年第10期97卷 453-459,I0009页

作者： yi yang Xia-Lin Zhong Lei Xu Zhuo-Lin yang Chong yan Jia-Qi huang School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Advanced Research Institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical EngineeringTsinghua UniversityBeijing 100084China yangtze River Delta Graduate School of Beijing Institute of Technology Jiaxing 314003ZhejiangChina

Fast charging is restricted primarily by the risk of lithium(Li)plating,a side reaction that can lead to the rapid capacity decay and dendrite-induced thermal runaway of lithium-ion batteries(LIBs).Investigation on the intrinsic mechanism and the position of Li plating is crucial to improving the fast rechargeability and safety of ***,we investigate the Li plating behavior in porous electrodes under the restricted transport of Li^(+).Based on the theoretical model,it can be concluded that the Li plating on the anodeseparator interface(ASI)is thermodynamically feasible and kinetically ***,the prior deposition of metal Li on the ASI rather than the anode-current collector interface(ACI)is verified *** order to facilitate the transfer of Li^(+)among the electrode and improve the utilization of active materials without Li plating,a bilayer asymmetric anode composed of graphite and hard carbon(GH)is *** and simulation results suggest that the GH hybrid electrode homogenizes the lithiated-rate throughout the electrode and outperforms the pure graphite electrode in terms of the rate performance and inhibition of Li *** work provides new insights into the behavior of Li plating and the rational design of electrode structure.

关键词： Graphite Hard carbon Fast charging Lithium plating Lithium-ion batteries

Optimal V_(2)O_(3) extraction by sustainable vanadate electrolysis in molten salts

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Tungsten 2024年第1期6卷 141-149页

作者： Bao-yan Feng Zhong-hua Zhao Yong-Zheng Jia Jia-Liang An Ming-Yong Wang State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China Beijing Key Laboratory of Green Recovery and Extraction of Rare and Precious Metals University of Science and Technology BeijingBeijing 100083China

Recently,an environmentally friendly electrolysis process of soluble vanadates is proposed and successfully confirmed for V_(2)O_(3) *** this paper,the solubilities of various vanadates(***_(3),Na_(4)V_(2)O_(7) and Na_(3)VO_(4))in NaCl molten salt are *** dependences of V_(2)O_(3) extraction on vanadate form,anode material and molten salt system are studied.A long-term electrolysis is carried *** result indicates that the solubilities of all vanadates are high and meet electrolytic *** to Na_(4)V_(2)O_(7) and Na_(3)VO_(4),NaVO_(3) exhibits larger current efficiency and lower electricity *** using SnO_(2) anode instead of graphite anode,the current efficiency of NaVO_(3) electrolysis can be increased to 58.1%and carbon pollution is avoided at 700℃.The extraction rate of V_(2)O_(3) reaches 81.3%after long-term electrolysis of 51 *** work optimizes the electrochemical preparation process of V_(2)O_(3) from various vanadates and contributes to the improvement of current efficiency and extraction rate.

关键词： Molten salt electrolysis Vanadate Vanadium trioxide Current efficiency

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

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World Journal of Diabetes 2024年第3期15卷 378-391页

作者： yan yi Tao Wang Wei Xu San-Hong Zhang Department of Ultrasonography The First Affiliated Hospital of Yangtze UniversityJingzhou 434000Hubei ProvinceChina Clinical Molecular Immunology Center Yangtze UniversityJingzhou 434023Hubei ProvinceChina Department of Pediatric Xiantao First People’s HospitalXiantao 433000Hubei ProvinceChina

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal *** a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic *** by means of placental transmission can changes in maternal hyperglycemia affect the *** are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after *** epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic *** paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

关键词： Gestational diabetes mellitus Placental functions Epigenetics Offspring development