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Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

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Chinese Journal of Chemistry 2024年第8期42卷 841-845页

作者： Yalan Peng Zuming lin Lili zhu Shiqing Han Sha-Hua Huang Ran Hong College of Biotechnology and Pharmaceutical Engineering Nanjing Tech UniversityNanjingJiangsu211816 China School of Environmental and Chemical Engineering Shanghai Institute of TechnologyShanghai201418 China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai200032 China Innovation Research Institute of Traditional Chinese Medicine(IRI) Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai201203 China

Comprehensive Summary,Valbenazine(Ingrezza),a potent and highly selective inhibitor of vesicular monoamine transporter type 2(VMAT2)through the active metabolite hydrotetrabenazine(HTBZ),has been approved for the treatment of tardive dyskinesia and,very recently,for chorea,which is associated with Huntington's *** numerous synthetic efforts dedicated to the synthesis of HTBZ,the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone ***,we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3-dipolar cycloaddition and enzymatic kinetic *** cascade process includes cycloaddition,N—O bond cleavage,and lactamization,which proved to be operationally *** allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroisoquinoline(THIQ)-fused piperidine in the production of medically significant compounds,such as yohimbine and reserpine.

关键词： Cycloaddition Chemoenzymatic Kinetic resolution Prodrugs VMAT2 inhibitor

Oblique impact breakage unification of nonspherical particles using discrete element method

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Particuology 2024年第7期90卷 61-71页

作者： Di Peng LiGe Wang Yuquan lin Chongqiang zhu Xizhong Chen Zhihui Liu Ruihuan Ge Shenzhen Research Institute of Shandong University Shenzhen 518057China Institute of Foundation Engineering China Academy of Building ResearchBeijing 100013China Ubiquitous Particle Ltd. TwickenhamLondon TW27AUUK Department of Smart Manufacturing and Engineering Software School of Qilu TransportationShandong UniversityJinan 250061China Department of Geotechnical Engineering Tongji UniversityShanghai 200092China School of Transportation and Civil Engineering Shandong Jiaotong UniversityJinan 250357China School of Science and Engineering University of DundeeDundee DD14HNUK Department of Chemical Engineering School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Chemical and Biological Engineering University of SheffieldSheffield S13JDUK

Particle breakage commonly occurs during processing of particulate materials,but a mechanistic model of particle impact breakage is not fully *** article presents oblique impact breakage characteristics of nonspherical particles using discrete element method(DEM)*** different particle shapes,***,cuboidal and cylindrical,are *** spheres are agglomerated with bridging bonds to model the breakage characteristics under impact *** effect of agglomerate shapes on the breakage pattern,damage ratio,and fragment size distribution is fully *** using a newly proposed oblique impact model,unified breakage master surfaces are theoretically constructed for all the particle shapes under oblique impact *** developed approach can be applied to modelling particulate processes where nonspherical particles and oblique impact breakage are prevailing.

关键词： Breakage master curve Nonspherical particle Oblique impact Equivalent velocity Discrete element method(DEM) Bonded contact model

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

linker gadolinium as charge channel and singlet oxygen activation site in graphitic carbon nitride for enhancing photocatalytic decomposition of tetracycline

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Journal of Rare Earths 2024年第5期42卷 827-837,I0001页

作者： Jianmin Luo Wenqin Li Xinglei Wang Eric Lichtfouse Donglan Huang Xiaoyuan Chen yi Zhang Lejie zhu Chuanyi Wang College of Chemistry and Civil Engineering Shaoguan UniversityShaoguan512005China Key Laboratory of Pollutant Chemistry and Environmental Treatment College of Chemistry and Environmental ScienceYili Normal UniversityYining 835000China College of Chemistry and Environmental Science Kashi UniversityKashi844006China CNRS IRDINRAEColl FranceCEREGEAix-Marseille UniversityAix en Provence13100France Guangzhou Institute of Industrial Intelligence(GIl) Guangzhou511400China

Reactive oxygen species are essential in photocatalytic water *** this paper,Gd doped carbon nitride(CN)photocatalysts were prepared by simple thermal polymerization for the photocatalytic degradation of tetracycline under visible light *** photodegradation rate of *** is as high as 95%in 18 min,and the photocatalytic performance is much higher than that of *** improvement of photocatalytic performance is mainly attributed to the fact that Gd ion implantation directly provides active sites for oxygen activation and induces the formation of N *** results of characterizations show that the introduction of Gd in CN can improve the conversion ability of activated oxygen,carrier separation and energy band structure ***,1.0GdCN photocatalyst can be employed for efficient photocatalytic synthesis of ***,three ways of photocatalytic degradation of tetracycline were revealed by high performance liquid chromatographymass *** work provides insights into the doping strategy of CN to improve the production of reactive oxygen species for environmental remediation.

关键词： Photocatalysis Tetracycline Hydrogen peroxide Gd doped CN Singlet oxygen Rare earths

Risk Factors of Enternal Nutrition Intolerance in Septic Patients:A Case-control Study

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Current Medical Science 2024年第2期44卷 328-332页

作者： Li-zhu WANG Yan XIANG Qian LI yi-rong zhu Jue FANG Xiao-dan LU Zhao-cai ZHANG Department of Nursing The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Critical Care Medicine The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of the Diagnosis and Treatment for Severe Trauma and Burn of Zhejiang Province Hangzhou 310009China Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine Hangzhou 310009China

Objective:This study aimed to investigate the incidence of enteral nutrition intolerance(ENI)in patients with sepsis and explore potential risk ***:A case-control study was conducted in patients with sepsis who were receiving enteral nutrition(EN)at a tertiary hospital in *** included patients were divided into the ENI group and the non-ENI *** and multivariate analyses were performed to identify the risk factors for ***:A total of 859 patients were included in the *** them,288(33.53%)patients experienced symptoms of ENI,including diarrhea,vomiting,bloating,and gastric *** regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H(APACHE H)score,thoracocentesis,and usage of cardiotonic drugs(namely,inotropes)were independent predictors of the ***:The incidence of ENI is relatively high in patients with sepsis,especially in those who have higher APACHE H scores,have undergone thoracocentesis,and have received inotropes.

关键词： sepsis enteral nutrition intolerance influencing factor

Relative position of seeds driven the seedling growth are mediated by root-leaf traits

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Journal of Plant Ecology 2024年第2期17卷 24-35页

作者： Jing zhu Xue-lin Wang Xing Jin Lan Jiang Hong-Yu lin Yang Hu Jin-Fu Liu Zhong-Sheng He College of Forestry Fujian Agriculture and Forestry UniversityFuzhou 350002China Key Laboratory of Fujian Universities for Ecology and Resource Statistics Fujian Agriculture and Forestry UniversityFuzhou 350002China Zhenjiang Natural Resources and Planning Bureau Economic and Technological Development Zone Branch Zhenjiang 212132China

Variations in plant traits are indicative of plant adaptations to forest environments,and studying their relationships with tree growth provides valuable insights into forest *** spatial arrangement of plant seeds within the forest litter or soil critically infuences the variations of root-leaf traits,thereby affecting the adaptive strategies of emerging ***,our current understanding of the impacts of individual root-leaf traits on seedling growth in different relative position,and whether these traits together affect growth,remains *** study focuses on the dominant tree species,Castanopsis kawakamii,within the Sanming *** Nature Reserve of *** present experiment aimed to examine the variations in root-leaf traits of seedling,focus on the relative positions of seeds within different layers:beneath or above the litter layer,or within the bare soil layer(without litter).Our fndings provided evidence supporting a coordinated relationship between root and leaf traits,wherein leaf traits varied in conjunction with root traits in the relative positions of ***,we observed that seedlings exhibited higher values for specifc leaf area and average root diameter,while displaying lower root tissue *** mixed model explained 86.1%of the variation in root-leaf traits,surpassing the variation explained by the relative ***,soil nitrogen acted as a mediator,regulating the relationship between seedling growth and root-leaf traits,specifcally leaf dry matter content and root tissue ***,future studies should consider artifcially manipulating tree species diversity based on root-leaf traits characteristics to promote forest recovery.

关键词： relative growth rate coordination leaf traits root traits soil nitrogen content seed relative positions

Impact factors and pathways of halonitromethanes formation from aspartic acid during LED-UV_(265)/chlorine disinfection

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Frontiers of Environmental Science & Engineering 2024年第1期18卷 129-144页

作者： Liangwen zhu Tao Wang Qian Tang Qing Wang lin Deng Jun Hu Chaoqun Tan Rajendra Prasad Singh Key Laboratory of Concrete and Prestressed Concrete Structures of Ministry of Education School of Civil EngineeringSoutheast UniversityNanjing 211189China College of Environment Zhejiang University of TechnologyHangzhou 310014China

Light emitting diode (LED-UV)/chlorine disinfection can replace UV/chlorine disinfection in wastewater treatment plants and water supply plants. Halonitromethanes (HNMs) are a class of novel nitrogenous disinfection by-products, which are characterized by higher cytotoxicity and genotoxicity than regulated disinfection by-products. Herein, the impact factors and pathways of HNMs formation from aspartic acid (ASP) were investigated during LED-UV_(265)/chlorine disinfection. The results showed that three types of chlorinated-HNMs (Cl-HNMs) were found during LED-UV265/chlorine disinfection, and their concentrations increased first and then declined as the reaction progressed. Cl-HNMs yields increased with increasing LED-UV_(265) intensity, free chlorine dosage, and ASP concentration, which declined with increasing pH (6.0–8.0). Meantime, the important impact of the coexisting ions contained in water matrices on HNMs formation from ASP was observed during LED-UV_(265)/chlorine disinfection. It was found that copper ions (Cu^(2+)) promoted Cl-HNMs formation. Furthermore, when bromide (Br–) appeared during LED-UV265/chlorine disinfection, nine types of HNMs were detected simultaneously. Moreover, Br– not only converted Cl-HNMs toward brominated (chlorinated)-HNMs and brominated-HNMs but also showed a marked effect on HNMs concentrations and species. Subsequently, the possible pathways of HNMs formation from ASP were proposed during LED-UV_(265)/chlorine disinfection. At last, it was proved that the formation trends of HNMs obtained in the real waters were similar to those in simulated waters. This work elaborated on the influence factors and pathways of HNMs formation, which is conducive to controlling the HNMs produced during LED-UV_(265)/chlorine disinfection.

关键词： LED-UV265 chlorine HNMs Aspartic acid Bromide Copper ions

Combination of Nitrogen-Rich Skeleton and Coordination Group:Synthesis of a High-Energy Primary Explosive Based on 1H-Tetrazole-5-Carbohydrazide

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Defence Technology（防务技术） 2024年第1期31卷 271-277页

作者： Tingwei Wang Zujia Lu Shu Bu Baolong Kuang Lu Zhang Zhenxin yi Kun Wang Shunguan zhu Jianguo Zhang State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China School of Chemical Engineering Nanjing University of Science and Technology200 Xiaolingwei StreetXuanwuNanjing 210094China Department of Chemistry Laboratory of Structure and Functional Regulation of Hybrid MaterialsAnhui UniversityMinistry of EducationHefei 230601China

The high energy coordination compounds Cu(TZCA)_(2)(ClO_(4))_(2)(ECCs-1) was prepared by 1H-tetrazole-5-carbohydrazide(TZCA) with a high energy skeleton and a strong coordination ability *** the same time,the reaction activity of the ligand was explored,and the single crystal structure of it and intermediate were *** structures of all substances were characterized by IR and *** the structure and composition of ECCs-1 are confirmed by ESP,AC,SEM and *** and chemical properties tests show that ECCs-1 has an acceptable thermal stability(T_(d)=177℃) and extremely sensitive mechanical stimulation(IS=1 J,FS=5 N).The comprehensive performance test results show that ECCs-1 has excellent initiation *** addition,the decomposition mechanism of ECCs-1 is explored from two aspects of experiment and theoretical calculation.

关键词： 1H-tetrazole-5-carbohydrazide Primary explosive Decomposition mechanism Coordination polymers Laser

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

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Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan Sun Xiu-Na Yang Shuang-Shuang Yang yi-zhu Lyu Bing Zhang Kai-Wen Liu Na Li Jia-Chen Cui Guang-Xiang Huang Cheng-lin Liu Jie Xu Jian-Qing Mi zhu Chen Xiao-Hu Fan Sai-Juan Chen Shuo Chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China National Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular ***,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based *** co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple *** we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated *** analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in ***-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived *** results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated