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Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1441-1456页

作者： Xin Zhuo yue Wu Xiujuan Fu Jianbin Li Yuxin Xiang Xiaoyu Liang Canquan Mao Yuhong jiang Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue *** is an urgent need to explore potential drug strategies for mitigating lung ***-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal ***,it has been rarely reported about the role of PAR2 in lung *** study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in ***,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of *** also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS ***,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

关键词： Protease-activated receptor 2(PAR2) CRISPR-Cas9 Gene editing Inflammation Acute lung inflammation NLRP3 Nanoparticles Drug delivery

PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han Zhang Kai Gao Shuang Wang yue-Hua Zhang Zhi-Xian Yang Ye Wu Yu-Wu jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases BeijingChina Children Epilepsy Center Peking University First HospitalBeijingChina Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina Center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular *** phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial *** We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation *** information obtained from these patients was analyzed along with that obtained from previously reported *** With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related *** patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental *** most common pathogenic missense variants were PACSI ***203Trp and PACS2 *** addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset *** The clinical phenotypes of the different PACS heterozygous missense variants were *** pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be *** findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

Temporal control of the Aux/IAA genes BnIAA32 and BnIAA34 mediates Brassica napus dual shade responses

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Journal of Integrative Plant Biology 2024年第5期66卷 928-942页

作者： Yafei Li Yiyi Guo yue Cao Pengguo Xia Dongqing Xu Ning Sun Lixi jiang Jie Dong Institute of Crop Science College of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310058China Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province College of Life Sciences and MedicineZhejiang Sci-TechUniversityHangzhou310018China State Key Laboratory of Crop Genetics and Germplasm Enhancement College of AgricultureNanjing Agricultural UniversityNanjing 210095China Key Laboratory of Growth Regulation and Transformation Research of Zhejiang Province School of Life SciencesWestlake UniversityHangzhou 310024China

Precise responses to changes in light quality are crucial for plant growth and *** example,hypocotyls of shade-avoiding plants typically elongate under shade *** this typical shade-avoidance response(TSR)has been studied in Arabidopsis(Arabidopsis thaliana),the molecular mechanisms underlying shade tolerance are poorly *** we report that ***(Brassica napus)seedlings exhibit dual shade *** addition to the TSR,*** seedlings also display an atypical shade response(ASR),with shorter hypocotyls upon perception of early-shade ***-wide selective sweep analysis indicated that ASR is associated with light and auxin ***,genetic studies demonstrated that phytochrome A(BnphyA)promotes ASR,whereas BnphyB inhibits *** ASR,YUCCA8 expression is activated by early-shade cues,leading to increased auxin *** inhibits hypocotyl elongation,as young *** seedlings are highly sensitive to ***,two non-canonical AUXIN/INDOLE-3-ACETIC ACID(Aux/IAA)repressor genes,BnIAA32 and BnIAA34,are expressed during this early ***32 and BnIAA34 inhibit hypocotyl elongation under shade conditions,and mutations in BnIAA32 and BnIAA34 suppress ***,our study demonstrates that the temporal expression of BnIAA32 and BnIAA34 determines the behavior of *** seedlings following shade-induced auxin biosynthesis.

关键词： Brassica napus high-density planting IAA32/34 light signal transduction shade response temporal gene expression

BAR:a branch-alternation-resorting algorithm for locality exploration in graph processing

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High Technology Letters 2024年第1期30卷 31-42页

作者：邓军勇 WANG Junjie jiang lin XIE Xiaoyan ZHOU Kai School of Electronic Engineering Xi'an University of Posts and TelecommunicationsXi'an 710121P.R.China School of Computer Xi'an University of Science and TechnologyXi'an 710054P.R.China School of Computer Xi'an University of Posts and TelecommunicationsXi'an 710121P.R.China

Unstructured and irregular graph data causes strong randomness and poor locality of data accesses in graph *** paper optimizes the depth-branch-resorting algorithm(DBR),and proposes a branch-alternation-resorting algorithm(BAR).In order to make the algorithm run in parallel and improve the efficiency of algorithm operation,the BAR algorithm is mapped onto the reconfigurable array processor(APR-16)to achieve vertex reordering,effectively improving the locality of graph *** paper validates the BAR algorithm on the GraphBIG framework,by utilizing the reordered dataset with BAR on breadth-first search(BFS),single source shortest paht(SSSP)and betweenness centrality(BC)algorithms for *** results show that compared with DBR and Corder algorithms,BAR can reduce execution time by up to 33.00%,and 51.00%*** terms of data movement,the BAR algorithm has a maximum reduction of 39.00%compared with the DBR algorithm and 29.66%compared with Corder *** terms of computational complexity,the BAR algorithm has a maximum reduction of 32.56%compared with DBR algorithm and53.05%compared with Corder algorithm.

关键词： graph processing vertex reordering branch-alternation-resorting algorithm(BAR) reconfigurable array processor

Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

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BIOCELL 2024年第8期48卷 1265-1273页

作者： SHAN jiang XIUFENG lin YANFEI CHEN XINNING LI JIALI KANG Department of Gynecology and Obstetrics The First Affiliated Hospital of Jinan UniversityGuangzhou510180China Reproductive Medical Center Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou510180China

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor *** has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and ***,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still ***:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian *** assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer *** pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer ***:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian *** experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this ***,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

关键词： Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer

Acupuncture for obesity and related diseases:Insight for regulating neural circuit

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Journal of Integrative Medicine 2024年第2期22卷 93-101页

作者： lin-yan jiang Jun Tian Ya-nan Yang Shao-hui Jia Qing Shu Department of Rehabilitation Medicine Zhongnan HospitalWuhan UniversityWuhan 430071Hubei ProvinceChina School of Sports Medicine Wuhan Sports UniversityWuhan 430079Hubei ProvinceChina Department of Traditional Chinese Medicine China Resources&Wu Gang General HospitalWuhan 430080Hubei ProvinceChina

Obesity is defined as abnormal or excessive fat accumulation that may impair *** is associated with numerous pathological changes including insulin resistance,fatty liver,hyperlipidemias,and other obesity-related *** comorbidities comprise a significant public health *** anti-obesity drugs have been limited by side effects that include depression,suicidal thoughts,cardiovascular complications and *** treatment has been shown to be effective for treating obesity and obesity-related conditions,while avoiding side ***,the mechanisms of acupuncture in treating obesity-related diseases,especially its effect on neural circuits,are not well understood.A growing body of research has studied acupuncture’s effects on the endocrine system and other mechanisms related to the regulation of neural *** this article,recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system,as well as some neural circuits involved,was *** on this,acupuncture’s potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed,leading to a deeper mechanistic understanding of acupuncture’s effects and providing insight and direction for future research about obesity.

关键词： Obesity Acupuncture Neural circuit Appetite Energy metabolism

Better engineering layered vanadium oxides for aqueous zinc‐ion batteries: Going beyond widening the interlayer spacing

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SmartMat 2024年第1期5卷 83-109页

作者： yue Guo Hanmei jiang Binbin Liu Xingyang Wang Yifu Zhang jianguo Sun John Wang Department of Materials Science and Engineering National University of SingaporeSingaporeSingapore State Key Laboratory of Fine Chemicals School of Chemical EngineeringDalian University of TechnologyDalianChina Institute of Materials Research and Engineering(IMRE) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore

Aqueous zinc‐ion batteries(ZIBs)are regarded as among the most promising candidates for large‐scale grid energy storage,owing to their high safety,low costs,and environmental *** the past decade,vanadium oxides,which are exemplified by V2O5,have been widely developed as a class of cathode materials for ZIBs,where the relatively high theoretical capacity and structural stability are among the main ***,there are considerable challenges in the construction of vanadium‐based ZIBs with high capacity,long lifespan,and excellent rate *** widenings of the interlayer spacing in the layered vanadium oxides by pre‐intercalations appear to have reached their limitations in improving the energy density and other key performance parameters of ZIBs,although various metal ions(Na+,Ca2+,and Al3+)and even organic cations/groups have been ***,we discuss the advances made more recently,and also the challenges faced by the high‐performance vanadium oxides(V2O5‐based)cathodes,where there are several strategies to improve their electrochemical performance ranging from the new structural designs down to sub‐nano‐scopic/molecular/atomic levels,including cation pre‐intercalation,structural water optimization,and defect engineering,to macroscopic structural *** key principles for an optimal structural design of the V2O5‐based cathode materials for high energy density and fast‐charging aqueous ZIBs are examined,aiming at paving the way for developing energy storage designed for those large scales,high safety,and low‐cost systems.

关键词： aqueous zinc‐ion batteries cations pre‐intercalation defect engineering structural water vanadium oxides

Chemoselective and Living/Controlled Polymerization of Alkenyl Methacrylates by the Phosphonium Ylide/Organoaluminum Lewis Pairs

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Chinese Journal of Polymer Science 2024年第2期42卷 159-167,I0005页

作者： Zhi-Kang Chen Wu-Chao Zhao Yi-ling Zhao Cong-Lei Liu Liu-Yin jiang yue-Tao Zhang Hong-Ping Zhu State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun130012China

Chemoselective,living/controlled polymerizations of allyl methacrylate(AMA) and vinyl methacrylate(VMA) with/without methyl methacrylate(MMA) by using the phosphonium ylide/organoaluminum based Lewis pairs(LPs) have been *** P-ylide-2/AIMe(BHT)_(2)(Pylide-2=Ph_(3)P=CHMe and BHT=2,6-iBu_(2)-4-MeC_(6)H_(2)O) was demonstrated to be superior by which homopolymers PAMAs(M_(n)=27.6-111.5kg/mol and ■=1.14-1.25) and PVMAs(M_(n)=28.4-78.4 kg/mol and ■=1.12-1.18) and block copolymers PMMA-b-PAMA,PAMA-b-PVMA,PAMA-bPMMA,PMMA-b-PAMA-b-PMMA,PAMA-b-PMMA-b-PAMA,and PAMA-b-PVMA-b-PAMA were *** the polymerizations,all of the monomers were reacted by the conjugated ester vinyl groups leaving intactly the nonconjugated acryloxy *** pendant acryloxy groups attached to the main chain enable further to post-functionalization by the AIBN-induced radical "thiol-ene" reaction using PhCH_(2)*** thiolether side group-containing polymers PAMA-SCH_(2)Ph and PAMA-SCH_(2)Ph-b-PMMA-b-PAMA-SCH_(2)Ph were thus prepared.

关键词： Phosphonium ylide Alkenyl methacrylate Chemoselectivity Living/controlled polymerization Post-functionalization

A Novel Location Method for Interline Power Flow Controllers Based on Entropy Theory

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Protection and Control of Modern Power Systems 2024年第3期9卷 70-81页

作者： Qiuyu Li Baohong Li Qin jiang Tianqi Liu Yin yue Yingmin Zhang Sichuan University the School of Electrical Engineering Sichuan UniversityChengdu 610065China the College of Electrical Engineering and Information Technology Sichuan University

As one of the new generation flexible AC transmission systems(FACTS)devices,the interline power flow controller(IPFC)has the significant advantage of simultaneously regulating the power flow of multiple ***,how to choose the appropriate location for the IPFC converters has not been discussed *** solve this problem,this paper proposes a novel location method for IPFC using entropy *** clarify IPFC’s impact on system power flow,its operation mechanism and control strategies of different types of serial converters are ***,to clarify the system power flow characteristic suitable for device location analysis,the entropy concept is *** this process,the power flow distribution entropy index is used as an optimization *** this index as a foundation,the power flow transfer entropy index is also generated and proposed for the IPFC location determination ***,electromechanical electromagnetic hybrid simulations based on ADPSS are implemented for *** are tested in a practical power grid with over 800 nodes.A modular multilevel converter(MMC)-based IPFC electromagnetic model is also established for precise *** results show that the proposed method can quickly and efficiently complete optimized IPFC location and support IPFC to determine an optimal adjustment in the N-1 fault cases.

关键词： Flexible alternative current transmission systems interline power flow controller modular multi-level converter optimized location method power flow transfer entropy