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Development and identification of two novel wheat-rye 6R derivative lines with adult-plant resistance to powdery mildew and high-yielding potential

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The Crop Journal 2024年第1期12卷 308-313页

作者： Guohao Han Jing Wang Hanwen Yan Tiantian Gu Lijun Cao Shiyu Liu Xiuquan Li yilin zhou Jieru Fan Zhipeng Shi Hong Liu Lihui Li Diaoguo An Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050021HebeiChina The National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China The State Key Laboratory for Biology of Plant Disease and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China

Powdery mildew,caused by Blumeria graminis f.***.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable pathogen.Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding.In this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages.Using genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,respectively.Compared with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits.Therefore,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.

关键词： Powdery mildew Secale cereale Triticum aestivum Wheat-rye 6R derivatives Agronomic performance

From aniline to phenol: carbon-nitrogen bond activation via uranyl photoredox catalysis

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National Science Review 2022年第6期9卷 74-80页

作者： Deqing Hu yilin zhou Xuefeng Jiang Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular Engineering East China Normal University State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences State Key Laboratory of Elemento-Organic Chemistry Nankai University

Carbon-nitrogen bond activation, via uranyl photoredox catalysis with water, enabled the conversion of 40 protogenetic anilines, 8 N-substituted anilines and 9 aniline-containing natural products/pharmaceuticals to the corresponding phenols in an ambient environment. A single-electron transfer process between a protonated aniline and uranyl catalyst, which was disclosed by radical quenching experiments and Stern-Volmer analysis, facilitated the following oxygen atom transfer process between the radical cation of protonated anilines and uranyl peroxide originating from water-splitting.18O labeling and15N tracking unambiguously depicted that the oxygen came from water and amino group left as ammonium salt. The 100-fold efficiency of the flow operation demonstrated the great potential of the conversion process for industrial synthetic application.

关键词： C−N bond activation C−O bond formation uranyl cations photoredox catalysis

Bispecific antibody drug conjugates:Making 1+1>2

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1965-1986页

作者： yilin Gu Zhijia Wang Yuxi Wang Targeted Tracer Research and Development Laboratory Institute of Respiratory HealthFrontiers Science Center for Disease-Related Molecular NetworkNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Frontiers Medical Center Tianfu Jincheng LaboratoryChengdu 610212China

Bispecific antibody‒drug conjugates(BsADCs)represent an innovative therapeutic category amalgamating the merits of antibody‒drug conjugates(ADCs)and bispecific antibodies(BsAbs).Positioned as the next-generation ADC approach,BsADCs hold promise for ameliorating extant clinical challenges associated with ADCs,particularly pertaining to issues such as poor internalization,off-target toxicity,and drug resistance.Presently,ten BsADCs are undergoing clinical trials,and initial findings underscore the imperative for ongoing refinement.This review initially delves into specific design considerations for BsADCs,encompassing target selection,antibody formats,and the linker–payload complex.Subsequent sections delineate the extant progress and challenges encountered by BsADCs,illustrated through pertinent case studies.The amalgamation of BsAbs with ADCs offers a prospective solution to prevailing clinical limitations of ADCs.Nevertheless,the symbiotic interplay among BsAb,linker,and payload necessitates further optimizations and coordination beyond a simplistic“1+1”to effectively surmount the extant challenges facing the BsADC domain.

关键词： Bispecific antibody drug conjugates Antibody drug conjugates Bispecific antibody Targeted therapy Safety HER2 EGFR

Transfer of disulfide bond formation modules via yeast artificial chromosomes promotes the expression of heterologous proteins inKluyveromyces marxianus

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mLife 2024年第1期3卷 129-142页

作者： Pingping Wu Wenjuan Mo Tian Tian Kunfeng Song yilin Lyu Haiyan Ren Jungang zhou Yao Yu Hong Lu State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghaiChina Shanghai Engineering Research Center of Industrial Microorganisms ShanghaiChina

Kluyveromyces marxianus is a food-safe yeast with great potential for producing heterologous proteins.Improving the yield in K.marxianus remains a challenge and incorporating large-scale functional modules poses a technical obstacle in engineering.To address these issues,linear and circular yeast artificial chromosomes of K.marxianus(KmYACs)were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K.marxianus.These modules contained up to seven genes with a maximum size of 15 kb.KmYACs carried telomeres either from K.marxianus or Tetrahymena.KmYACs were transferred successfully into K.marxianus and stably propagated without affecting the normal growth of the host,regardless of the type of telomeres and configurations of KmYACs.KmYACs increased the overall expression levels of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins.In high-density fermentation,the use of KmYACs resulted in a glucoamylase yield of 16.8 g/l,the highest reported level to date in K.marxianus.Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased flavin adenine dinucleotide biosynthesis,enhanced flux entering the tricarboxylic acid cycle,and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins.Consistently,supplementing lysine or arginine further improved the yield.Therefore,KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research.Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins,and this strategy may be applied to optimize other microbial cell factories.

关键词： disulfide bond formation expression of heterologous proteins Kluyveromyces marxianus telomere yeast artificial chromosome

Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

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Neural Regeneration Research 2024年第2期19卷 434-439页

作者： Chenxi Zhao Tiangang zhou Ming Li Jie Liu Xiaoqing Zhao yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng Department of Orthopedics Tianjin Medical University General HospitalTianjinChina International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Orthopedic Research Center of Shandong University Cheeloo College of MedicineDepartment of OrthopedicsQilu Hospital of Shandong UniversityJinanShandong ProvinceChina

Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

关键词： argatroban astrogliosis JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury thrombin vimentin

Mitochondrial sensitive probe with aggregation-induced emission characteristics for early brain diagnosis of Parkinson’s disease

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Aggregate

Aggregate 2024年第1期5卷 216-227页

作者： Liwen Huang Yutong zhou Di Jiao Jing Ren yilin Qi Heping Wang Yang Shi Dan Ding Xue Xue State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjinP.R.China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of Educationand College of Life SciencesNankai UniversityTianjinP.R.China

The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.

关键词： aggregation-induced emission early diagnosis Parkinson’s disease

Hadoop-based secure storage solution for big data in cloud computingg environment

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Digital Communications and Networks 2024年第1期10卷 227-236页

作者： Shaopeng Guan Conghui Zhang yilin Wang Wenqing Liu School of Information and Electronic Engineering Shandong Technology and Business UniversityYantai264003China

In order to address the problems of the single encryption algorithm,such as low encryption efficiency and unreliable metadata for static data storage of big data platforms in the cloud computing environment,we propose a Hadoop based big data secure storage scheme.Firstly,in order to disperse the NameNode service from a single server to multiple servers,we combine HDFS federation and HDFS high-availability mechanisms,and use the Zookeeper distributed coordination mechanism to coordinate each node to achieve dual-channel storage.Then,we improve the ECC encryption algorithm for the encryption of ordinary data,and adopt a homomorphic encryption algorithm to encrypt data that needs to be calculated.To accelerate the encryption,we adopt the dualthread encryption mode.Finally,the HDFS control module is designed to combine the encryption algorithm with the storage model.Experimental results show that the proposed solution solves the problem of a single point of failure of metadata,performs well in terms of metadata reliability,and can realize the fault tolerance of the server.The improved encryption algorithm integrates the dual-channel storage mode,and the encryption storage efficiency improves by 27.6% on average.

关键词： Big data security Data encryption Hadoop Parallel encrypted storage Zookeeper

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

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Journal of Sport and Health Science 2024年第2期13卷 222-232页

作者： Xinyi Jin yilin Chen Hongliang Feng Mingqing zhou Joey W.Y.Chang Yaping Liu Alice Pik Shan Kong Xiao Tan Yun-Kwok Wing Yannis Yan Liang Jihui Zhang Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Cardiovascular InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China School of Medicine South China University of TechnologyGuangzhou 510641China Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510180China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510282China Guangdong Mental Health Center Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510120China Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medical Sciences Uppsala UniversityUppsala 75185Sweden Department of Big Data in Health Science Zhejiang University School of Public HealthHangzhou 310058China Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou 510260China

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

关键词： Light physical activity Sleep duration Triaxial accelerometer Type 2 diabetes UK Biobank

Single-Nucleus RNA Sequencing Reveals Cardiac Macrophage Landscape in Hypoplastic Left Heart Syndrome

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Congenital Heart Disease 2024年第2期19卷 233-246页

作者： Xiaozhuo Xu yilin Huang Xu Han First Clinical Medical College Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210008China Department of Geriatrics Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210029China

Background:Hypoplastic left heart syndrome(HLHS)is one of the most challenging congenital heart diseases in clinical treatment.In cardiac tissues,resident macrophages fulfill critical functions in maintaining a stable cardiac state and have strong regenerative capacity and organ specificity.However,the molecular mechanisms of macro-phages in HLHS remained unclear.Methods:Single-nucleus RNA sequencing(snRNA-seq)data of HLHS and healthy control(donors)samples obtained from the Gene Expression Omnibus(GEO)database were normalized and clustered using the Seurat package.The“FindMarkers”function was used to screen differentially expressed genes(DEGs)between the HLHS and donor groups and to analyze the functional enrichment of the set of genes of interest.Finally,cell-cell communication,pseudotime,and single-cell regulatory network inference and cluster-ing(SCENIC)analyses were used to study the mechanisms of macrophages in HLHS.Results:Based on the snRNA-seq data of HLHS and donors,we identified a total of 9 cell clusters,among which the proportion of macrophages was significantly less in the HLHS group than in the control group.Subdivision of macrophage subpopulations(Macrophages 1,2,and 3)showed that Macrophages 1 was mainly involved in nervous system development,angiogenesis,and apoptotic processes.In addition,analysis of communication between Macro-phages 1 and cardiomyocytes revealed that ligand-acceptor pairs such as GAS6/AXL,IL6,IGF1,THY1,and L1CAM were present only in the donor group.Finally,pesudotime and SCENIC analyses demonstrated that FOXO3 and ELF2 played a critical role for Macrophages 1 to maintain cardiac function in patients with HLHS.Conclusion:Our study improved the current understanding of the molecular mechanisms of macrophage devel-opment in HLHS,showing that manipulating the regulatory role of macrophages in the heart can be a novel treat-ment for HLHS.

关键词： Hypoplastic left heart syndrome single-nucleus RNA sequencing macrophage cellular subpopulation transcription factor