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The endoplasmic reticulum membrane protein complex subunit Emc6 is essential for rhodopsin localization and photoreceptor cell survival

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Genes & Diseases 2024年第2期11卷 1035-1049页

作者： Kuanxiang Sun Lu Liu Xiaoyan Jiang Heting Wang lin Wang Yeming Yang Wenjing Liu lin Zhang Xiaohui Zhao Xianjun zhu Health Management Center Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Key Laboratory of Tibetan Medicine Research Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine ResearchNorthwest Institute of Plateau BiologyXiningQinghai 810008China The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Center for Medical GeneticsSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduSichuan 610072China Department of Ophthalmology The First People's Hospital of ShangqiuShangqiuHenan 476000China

The endoplasmic reticulum(ER)membrane protein complex(EMC)is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane *** EMC subunit EMC6 is one of the core members of EMC and forms an enclosed hydrophilic vestibule in cooperation with *** studies demonstrating that deletion of EMC3 led to rhodopsin mislocalization in rod photoreceptors of mice,the precise mechanism leading to the failure of rhodopsin trafficking remains ***,we generated the first rod photoreceptor-specific knockout of Emc6(RKO)and cone photoreceptor-specific knockout of Emc6(CKO)mouse *** of Emc6 in rod photoreceptors led to progressive shortening of outer segments(OS),impaired visual function,mislocalization and reduced expression of rhodopsin,and increased gliosis in rod *** addition,CKO mice displayed the progressive death of cone photoreceptors and abnormal localization of cone opsin ***,proteomics analysis of the RKO mouse retina illustrated that several cilium-related proteins,particularly anoctamin-2(ANO2)and transmembrane protein 67(TMEM67),were significantly down-regulated prior to OS *** rod photoreceptor cilia and mislocalized membrane disc proteins were evident in RKO *** data revealed that in addition to monitoring the synthesis of rhodopsin-dominated membrane disc proteins,EMC6 also impacted rod photoreceptors'ciliogenesis by regulating the synthesis of membrane proteins associated with cilia,contributing to the mislocalization of membrane disc proteins.

关键词： ANO2 Cilium EMC6 ER membrane protein complex Mislocalization Photoreceptor degeneration TMEM67

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Differential expression of miRNAs and mRNAs in the livers of largemouth bass Micropterus salmoides under heat stress

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Journal of Oceanology and Limnology 2024年第2期42卷 594-608页

作者： Xuqian ZHAO Zijie lin Caijuan LI Hao zhu lingling LI Wenjia MAO Qufei linG School of Biology and Basic Medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Global warming threatens freshwater ecosystems and compromises fish *** elucidate the role of miRNAs in the livers of heat stressed largemouth bass,juvenile fish was subject to heat stress under 37°*** mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress *** gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles.A total of 406 differentially expressed genes(DEGs)were discovered,of which 212 were up-regulated and 194 were *** of the DEGs were significantly implicated in the regulation of“protein processing in endoplasmic reticulum”,“proteasome”,“steroid biosynthesis”,and“ornithine decarboxylase inhibitor activity”*** addition,47 differentially expressed miRNAs(DEMs)were identified in largemouth bass livers under heat stress,including 21 up-regulated and 25 down-regulated miRNAs.A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in“protein degradation”,“calcium ion regulation”,“cell apoptosis”,and“lipid metabolism”.Moreover,this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat *** study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress.

关键词： heat stress largemouth bass miRNA-mRNA interaction

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Distributed Application Addressing in 6G Network

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China Communications 2024年第4期21卷 193-207页

作者： Liu Jie Chen Sibo Liu Yuqin Mo Zhiwei lin Yilin zhu Hongmei He Yufeng China Telecom Research Institute Guangzhou 510632China

To ensure the extreme performances of the new 6G services,applications will be deployed at deep edge,resulting in a serious challenge of distributed application *** paper traces back the latest development of mobile network application addressing,analyzes two novel addressing methods in carrier network,and puts forward a 6G endogenous application addressing scheme by integrating some of their essence into the 6G network architecture,combining the new 6G capabilities of computing&network convergence,endogenous intelligence,and communication-sensing *** paper further illustrates how that the proposed method works in 6G networks and gives preliminary experimental verification.

关键词： application addressing CNC(Computing&Network Convergence) DNS(Domain Name System) ICN(Information-Centric Network) 6G

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A reduced combustion mechanism of ammonia/diesel optimized with multi-objective genetic algorithm

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Defence Technology（防务技术） 2024年第4期34卷 187-200页

作者： Wanchen Sun Shaodian lin Hao Zhang Liang Guo Wenpeng zeng Genan zhu Mengqi Jiang State Key Laboratory of Automotive Simulation and Control Jilin UniversityChangchun 130025China

For the deep understanding on combustion of ammonia/diesel,this study develops a reduced mechanism of ammonia/diesel with 227 species and 937 *** sub-mechanism on ammonia/interactions of N-based and C-based species(N—C)/NOx is optimized using the Non-dominated Sorting Genetic Algorithm II(NSGA-II)with 200 *** optimized mechanism(named as 937b)is validated against combustion characteristics of ammonia/methane(which is used to examine the accuracy of N—C interactions)and ammonia/diesel *** ignition delay times(IDTs),the laminar flame speeds and most of key intermediate species during the combustion of ammonia/methane blends can be accurately simulated by 937b under a wide range of *** for ammonia/diesel blends with various diesel energy fractions,reasonable predictions on the IDTs under pressures from 1.0 MPa to5.0 MPa as well as the laminar flame speeds are also achieved by *** particular,with regard to the IDT simulations of ammonia/diesel blends,937b makes progress in both aspects of overall accuracy and computational efficiency,compared to a detailed ammonia/diesel *** kinetic analysis reveals that the reaction pathway of ammonia during the combustion of ammonia/diesel blend mainly differs in the tendencies of oxygen additions to NH_2 and NH with different equivalence ratios.

关键词： Ammonia Diesel Combustion Kinetic mechanism Multi-objective optimization

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Privacy-Preserving Federated Mobility Prediction with Compound Data and Model Perturbation Mechanism

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China Communications 2024年第3期21卷 160-173页

作者： Long Qingyue Wang Huandong Chen Huiming Jin Depeng zhu lin Yu Li Li Yong Beijing National Research Center for Information Science and Technology(BNRist) Department of Electronic EngineeringTsinghua UniversityBeijing 100084China China Mobile Research Beijing 100032China

Human mobility prediction is important for many ***,training an accurate mobility prediction model requires a large scale of human trajectories,where privacy issues become an important *** rising federated learning provides us with a promising solution to this problem,which enables mobile devices to collaboratively learn a shared prediction model while keeping all the training data on the device,decoupling the ability to do machine learning from the need to store the data in the ***,existing federated learningbased methods either do not provide privacy guarantees or have vulnerability in terms of privacy *** this paper,we combine the techniques of data perturbation and model perturbation mechanisms and propose a privacy-preserving mobility prediction algorithm,where we add noise to the transmitted model and the raw data collaboratively to protect user privacy and keep the mobility prediction *** experimental results show that our proposed method significantly outperforms the existing stateof-the-art mobility prediction method in terms of defensive performance against practical attacks while having comparable mobility prediction performance,demonstrating its effectiveness.

关键词： federated learning mobility prediction privacy

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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

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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

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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

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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

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Spin effect on redox acceleration and regioselectivity in Fe-catalyzed alkyne hydrosilylation

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National Science Review 2024年第2期11卷 155-167页

作者： Peng He Meng-Yang Hu Jin-Hong Li Tian-Zhang Qiao Yi-lin Lu Shou-Fei zhu Frontiers Science Center for New Organic Matter State Key Laboratory and Institute of Elemento-Organic Chemistry Nankai University

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively,and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.

关键词： spin effect spin-delocalization spin crossover iron-catalysis alkyne hydrosilylation

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