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β-Carboline alkaloids from the roots of Peganum harmala L.

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Chinese Journal of Natural Medicines 2024年第2期22卷 171-177页

作者： li Shengge ZHANG Qin WANG Yuetong liN Bin li Dahong hua Huiming HU xu Henan Key Laboratory of Zhang Zhongjing Formulate and Herbs for Immunoregulation Zhang Zhongjing Traditional School of Chinese MedicineNanyang Institute of TechnologyNanyang 473004China Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

关键词： β-Carboline alkaloids Peganum harmala Structure elucidation Cytotoxic activity

Neutron irradiation influence on high-power thyristor device under fusion environment

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Nuclear Science and Techniques 2024年第4期35卷 65-81页

作者： Wei Tong hua li Meng xu Zhi-Quan Song Bo Chen School of Electrical Engineering and Automation Hefei University of TechnologyHefei 230009China Institute of Plasma Physics Hefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China University of Science and Technology of China Hefei 230026China

Because of their economy and applicability,high-power thyristor devices are widely used in the power supply systems for large fusion devices.When high-dose neutrons produced by deuterium–tritium(D–T)fusion reactions are irradiated on a thyristor device for a long time,the electrical characteristics of the device change,which may eventually cause irreversible damage.In this study,with the thyristor switch of the commutation circuit in the quench protection system(QPS)of a fusion device as the study object,the relationship between the internal physical structure and external electrical parameters of the irradiated thyristor is established.Subsequently,a series of targeted thyristor physical simulations and neutron irradiation experiments are conducted to verify the accuracy of the theoretical analysis.In addition,the effect of irradiated thyristor electrical characteristic changes on the entire QPS is studied by accurate simulation,providing valuable guidelines for the maintenance and renovation of the QPS.

关键词： Fusion device Neutron irradiation effects Thyristor Quench protection

Microstructure and property of laser additive manufactured alloy Ti–6Al–2V–1.5Mo–0.5Zr–0.3Si after aged at different temperatures

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Rare Metals 2024年第5期43卷 2275-2281页

作者： Guo-Chao li xu Cheng hua-Ming Wang National Engineering Laboratory of Additive Manufacturing for Large Metallic Components and Engineering Research Center ofMinistry of Education on Laser Direct Manufacturing for Large Metallic Components School of Materials Science and Engineering Beihang University

The solid solution and aging treatment for conventional manufacturing processes might not be suitable for laser additive manufactured titanium alloys due to the different lamellar microstructures. In this study, the influence of aging temperatures (600, 700 and 800°C) on microstructure and mechanical properties of titanium alloy Ti–6Al–2V–1.5Mo–0.5Zr–0.3Si was investigated. The results indicate that after solid solution treatment at 970°C followed by water quenching, the alloy mainly consists of coarsening lamellar a phase in martensite a'matrix. Aging at 600°C will not change the size of primary lamellar a phase but lead to huge amount of secondary a phases (as)generating with very fine microstructure. By increasing the aging temperature, the number of asdecreases but with coarsened microstructures. When aged at 800°C, the width of the asphase reaches 350 nm, almost 7 times wider than that aged at 600°C. The changing size of asobviously influences the property of the alloy. The fine asleads to high strength and microhardness but low plasticity, and specimen aged at 700°C with suitable assize has the best comprehensive properties.

关键词： α + β titanium alloy Laser additive manufacturing Solid solution and aging treatment Microstructure Room temperature tensile property

Bortezomib depended on PRDM1 and TP53 to exert therapeutic effect in activated B-cell-like diffuse large B-cell lymphoma

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Genes & Diseases 2024年第2期11卷 550-553页

作者： Jing Tang Yue li Jiazhu Wu Haorui Shen hua Yin Jinhua liang li Wang Jianyong li Yi Xia Wei xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BliMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior survival.However,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of PRDM1.We investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal inactivation.We first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

关键词： PRDM1 TP53 therapeutic

Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

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Genes & Diseases 2024年第4期11卷 116-119页

作者： Yi Xia li Wang Jinhua liang Haorui Shen Jiazhu Wu hua Yin Yue li huayuan Zhu Jianyong li Wei xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical outcomes.Patients who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely dismal prognosis.The heterogeneous clinical outcomes of DLBCL patients result from variable genetic profiles.

关键词： lymphoma diagnosis clinical

Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation

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Asian Journal of Andrology 2024年第1期26卷 25-33页

作者： Kun Zhang Xiu-hua xu Jian Wu Ning Wang Gang li Gui-Min Hao Jin-Feng Cao Hebei Key Laboratory of Infertility and Genetics Department of Reproductive MedicineSecond Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Reproductive Medicine Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000China Department of Neurology The 980th Hospital of the People's Liberation Army Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang 050000China.

The sperm DNA fragmentation index(DFI)is a metric used to assess DNA fragmentation within sperm.During in vitro fertilizationembryo transfer(IVF-ET),high sperm DFI can lead to a low fertilization rate,poor embryo development,early miscarriage,etc.A kinase anchoring protein(AKAP)is a scaffold protein that can bind protein kinase A(PKA)to subcellular sites of specific substrates and protects the biophosphorylation reaction.Sperm protein antigen 17(SPA17)can also bind to AKAP.This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI(H-DFI)patients during IVF-ET.In addition,the study investigates the expression of AKAP,protein kinase A regulatory subunit(PKARIl),and SPA17 between H-DFI and low sperm DFI(L-DFI)patients.SPA17 at the transcriptional level is abnormal,the translational level increases in H-DFI patients,and the expression of AKAP4/PKARIl protein decreases.H,O,has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI.It indicates that H,O,increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARIl protein expression.These processes inhibit sperm capacitation and reduce acrosomal reactions.Embryo culture data and IVF outcomes have been documented.The H-DFI group has a lower fertilization rate.Therefore,the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARIl proteins,blocked sperm capacitation,and reduced occurrence of acrosome reaction.

关键词： AKAP PKA SPA17 sperm capacitation sperm DNA fragmentation index

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 mortality.The 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 model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions 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

Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

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Science China Chemistry 2024年第6期67卷 2079-2091页

作者： liwei xu Xinxin xu hua Kuang Chuanlai xu Xiaoling Wu State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and Technology Jiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu Province Jiangnan UniversityWuxi214122China

Chiral pollutants often pose significant differential environmental health risks.In this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically investigated.Firstly,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was revealed.The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of S-configuration.Meanwhile,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine.Thirdly,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.

关键词： neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk

Heteroepitaxial growth of Au@Pd core–shell nanocrystals with intrinsic chiral surfaces for enantiomeric recognition

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Rare Metals 2024年第1期43卷 225-235页

作者： Feng-Xia Wu Feng-hua li Xia-li Lv Qi-Xian Zhang Guo-Bao xu Wen-Xin Niu State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Shaoxing Institute of Technology Shanghai UniversityShaoxing 312000China University of Science and Technology of China Hefei 230026China School of Materials Science and Engineering Shanghai UniversityShanghai 200436China Zhejiang Institute of Advanced Materials Shanghai UniversityJiashan 314113China University of Chinese Academy of Sciences Beijing 100039China

Noble metal surfaces with intrinsic chirality serve as an ideal candidate for investigating enantioselective chemistry due to their superior chemical durability and high catalytic activity.Recently,significant advance has been made in synthesizing metal nanocrystals with intrinsic chirality.Nonetheless,the majority reports are limited to gold.Herein,through a heteroepitaxial growth strategy,the synthesis of metal nanocrystals with intrinsic chirality to palladium was extended for the first time and their application in enantioselective recognition was demonstrated.The heteroepitaxial growth strategy allows for transferring the chirality of homochiral Au nanocrystals to Au@Pd core–shell nanocrystals.By employing the chiral Au@Pd nanocrystals as enantiomeric recognizing elements,a series of electrochemical sensors for chiral discrimination were developed.Under optimal conditions,the peak potential between D-dihydroxyphenylalanine(D-DOPA)and L-dihydroxyphenylalanine(L-DOPA)is about 80 m V,and the peak current of D-DOPA is 2 times as much as that of L-DOPA,which enables the determination of the enantiomeric excess(EE,%)of L-DOPA.Overall,this report not only introduces a heteroepitaxial growth strategy to synthesize metal nanocrystals with intrinsic chirality,but also demonstrates the superior capability of integrating intrinsic chirality and catalytic properties into metal nanocrystals for chiral recognition.

关键词： Core–shell nanostructures Chirality transfer Electrochemical sensors Chiral recognition Chiroplasmonics