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Efficient genome editing in rice with miniature Cas12f variants

aBIOtECH 2024年第2期5卷 184-188页

作者： Zhengyan Ye Yuanyan Zhang Shiqi He Shaokang Li Longjiong luo Yanbiao Zhou Junjie tan Jianmin Wan Sanya Institute of Nanjing Agricultural University State Key Laboratory of Crop Genetics&Germplasm Enhancement and UtilizationProvince and Ministry Co-sponsored Collaborative Innovation Center for Modern Crop ProductionNanjing Agricultural UniversityNanjing 210095China Zhongshan Biological Breeding Laboratory No.50 Zhongling StreetNanjing 210014China Key Laboratory of Southern Rice Innovation&Improvement Ministry of Agriculture and Rural Affairs/Hunan Engineering Laboratory of Disease and Pest Resistant Rice BreedingYuan Longping High-Tech Agriculture Co.LtdChangsha 410001China

Genome editing,particularly using the CRISPR/Cas system,has revolutionized biological research and crop *** the widespread use of CRISPR/Cas9,it faces limitations such as PAM sequence requirements and challenges in delivering its large protein into plant *** hypercompact Cas12f,derived from Acidibacillus sulfuroxidans(AsCas12f),stands out due to its small size of only 422 amino acids and its preference for a t-rich motif,presenting advantageous features over ***,its editing efficiency is extremely low in *** studies have generated two AsCas12f variants,AsCas12f-YHAM and AsCas12f-HKRA,demonstrating higher editing efficiencies in mammalian cells,yet their performance in plants remains *** this study,through a systematic investigation of genome cleavage activity in rice,we unveiled a substantial enhancement in editing efficiency for both AsCas12f variants,particularly for AsCas12f-HKRA,which achieved an editing efficiency of up to 53%.Furthermore,our analysis revealed that AsCas12f predominantly induces deletion in the target DNA,displaying a unique deletion pattern primarily concentrated at positions 12,13,23,and 24,resulting in deletion size mainly of 10 and 11 bp,suggesting significant potential for targeted DNA deletion using *** findings expand the toolbox for efficient genome editing in plants,offering promising prospects for precise genetic modifications in agriculture.

关键词： CRISPR/Cas Cas12 AsCas12f Rice Genome editing

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27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer

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Journal of Pharmaceutical Analysis 2024年第3期14卷 371-388页

作者： Haonan Ruan Jing Zhang Yunyun Wang Ying Huang Jiashuo Wu Chunjiao He tongwei Ke Jiaoyang luo Meihua Yang Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100193China

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public ***,the mechanisms behind ZEN-induced intestinal immunotoxicity remain *** this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day *** a duration of 14 *** results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the ***,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(Pt upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(Pthe presence of 27-hydroxycholesterol(27-HC)in the intestine(Pt was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ***,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung *** findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of t lymphocyte activation within the rat ***,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

关键词： Zearalenone Intestinal immunosuppression Apolipoprotein E Bioinformatics analysis Cancer

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Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-tian Zhu Hao Li Jing-Zhi luo Yu Yang Yang An Xi Wang Kai Wang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China State Key Laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin *** as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical *** inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic *** review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with ***,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic *** review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage tissue engineering Disease modelling Regenerative medicine

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng luo Jijun Shi Qifei Cong Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. the crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. this review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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Self-powered wireless environmental monitoring system for in-service bridges by galloping piezoelectric-triboelectric hybridized energy harvester

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Science China(technological Sciences) 2024年第5期67卷 1498-1509页

作者： HUANG KangXu WANG XiaoFei WANG Li ZHOU YuHui LIU FuHai CHANG ShiYuan ZHU Juntao ZHOU YuXuan ZHANG He luo JiKui College of Civil Engineering and Architecture Zhejiang UniversityHangzhou310058China Anhui transport Consulting&Design Institute Co. Ltd.Hefei230088China College of Electronics&Information Hangzhou Dianzi UniversityHangzhou310018China Center for Balance Architecture Zhejiang UniversityHangzhou310058China College of Information Science&Electronic Engineering Zhejiang UniversityHangzhou310027China

the energy harvesting technology for the ubiquitous natural wind enables a desirable solution to the issue of distributed sensors in the bridge environmental sensing Internet of things(Io t)system being restricted to conventional energy *** this work,a self-powered system based on a compact galloping piezoelectric-triboelectric energy harvester(GPtEH)is developed to achieve efficient wind energy *** GPtEH is constructed on the prototype of a cantilever structure with piezoelectric macro-fiber composite(MFC)sheets and a rectangular bluff body with triboelectric nanogenerators(tENGs).through a special swing-type structural design with iron blocks inside the bluff body,the GPtEH exhibits preferable aerodynamic behavior and excellent energy conversion efficiency,compared to conventional cantilever kind of piezoelectric wind energy harvester(PWEH).the GPtEH also demonstrates the capability of high output power density(PEH of 23.65 W m^(-2)and tENG of 1.59 W m^(-2)),superior response wind speed(about 0.5 m s^(-1)),and excellent long-term stability(over 14000 cyclic tests).Furthermore,a power management system is developed to efficiently utilize the output energy from GPtEH to power the sensors and wirelessly transmit environmental data to the *** proposed GPtEH-powered system exhibits a great potential for the bridge environmental monitoring and Io t technologies.

关键词： self-powered hybrid nanogenerator triboelectric nanogenerator macro-fiber composite wireless environmental monitoring system

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Strong Antiferromagnetic Exchange-Coupling Observed in Hydride-Bridged Dimeric Dysprosium(Ⅲ)Single-Molecule Magnet

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Chinese Journal of Chemistry 2024年第4期42卷 391-396页

作者： Qian-Cheng luo Ke-Xin Yu Peng-Bo Jin Ye-Ye Liu Yuan-Qi Zhai Yan-Zhen Zheng Frontier Institute of Science and technology State Key Laboratory of Electrical Insulation and Power EquipmentXi'an Key Laboratory of Electronic Devices and Materials ChemistrySchool of Chemistry and School of PhysicsXi'an Jiaotong University99 Yanxiang RoadXi'anShaanxi710054 China

One dihydride-bridged dimeric Dy(Ⅲ)guanidinate complex,formulated as[{(Me_(3)Si)_(2)NC(NiPr)_(2)}_(2)Dy(μ-H)]_(2)(1Dy),was successfully isolated and the introduction of hydride bridges significantly reduces the intramolecular Dy(Ⅲ)…Dy(Ⅲ)distance to only 3.688(1)Å.to investigate the effect of such a short Dy(Ⅲ)…Dy(Ⅲ)distance on magnetism,we also prepared its dibromide-bridged analogue[{(Me_(3)Si)_(2)NC(NiPr)_(2)}_(2)Dy(μ-Br)]_(2)(2Dy),which has a much longer Dy(Ⅲ)…Dy(Ⅲ)distance of 4.605(4)Å.Surprisingly,2Dy demonstrates much larger effective energy barrier for magnetization reversal(U_(eff))and higher blocking temperature(t_(B)).the worse performance of 1Dy is attributed to the concerted effect of strong antiferromagnetic interactions between Dy(Ⅲ)ions(J_(total)=–2.683 cm^(–1))and the unparallel arrangement of magnetic principle axes of the Dy(Ⅲ)ions for 1Dy.

关键词： Single-molecule magnets Lanthanides Guanidinate ligand Hydride bridge Magnetic properties Ab initio calculations

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towards the performance limit of catenary meta-optics via field-driven optimization

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Opto-Electronic Advances 2024年第5期7卷 33-42页

作者： Siran Chen Yingli Ha Fei Zhang Mingbo Pu Hanlin Bao Mingfeng Xu Yinghui Guo Yue Shen Xiaoliang Ma Xiong Li Xiangang luo National Key Laboratory of Optical Field Manipulation Science and technology Chinese Academy of SciencesChengdu 610209China State Key Laboratory of Optical technologies on Nano-Fabrication and Micro-Engineering Institute of Optics and ElectronicsChinese Academy of SciencesChengdu 610209China College of Materials Science and Opto-Electronic technology University of Chinese Academy of SciencesBeijing 100049China Research Center on Vector Optical Fields Institute of Optics and ElectronicsChinese Academy of SciencesChengdu 610209China Department of Electrical and Computer Engineering University of California Los Angeles(UCLA)Los AngelesCalifornia 90095USA

Catenary optics enables metasurfaces with higher efficiency and wider bandwidth,and is highly anticipated in the imaging system,super-resolution lithography,and broadband ***,the periodic boundary approximation without considering aperiodic electromagnetic crosstalk poses challenges for catenary optical devices to reach their performance ***,perfect control of both local geometric and propagation phases is realized through field-driven optimization,in which the field distribution is calculated under real boundary *** from other optimization methods requiring a mass of iterations,the proposed design method requires less than ten iterations to get the efficiency close to the optimal *** on the library of shape-optimized catenary structures,centimeter-scale devices can be designed in ten seconds,with the performance improved by ~15%.Furthermore,this method has the ability to extend catenary-like continuous structures to arbitrary polarization,including both linear and elliptical polarizations,which is difficult to achieve with traditional design *** provides a way for the development of catenary optics and serves as a potent tool for constructing high-performance optical devices.

关键词： catenary optics catenary structures field-driven optimization

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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen Research Institute of Xiamen University Shenzhen 518057China Division of Urology and Department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation Laboratory for Sciences and technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology therapeutic proteins Gene therapy Nanomedicine

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Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic targets

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Infectious Diseases & Immunity 2024年第2期4卷 61-68页

作者： Runpeng Han Fei luo Haisheng Yu Yajun Yan Yan Gong Conghua Xie Liang Cheng Department of Radiation and Medical Oncology Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Zhongnan Hospital of Wuhan UniversityState Key Laboratory of VirologyWuhan UniversityWuhan 430071China Guangzhou Eighth People's Hospital Guangzhou Medical UniversityGuangzhou 510440China Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health ***,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic ***:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 *** generated a GEM by integrating an HIV-1 production reaction into CD4+t cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion *** analysis was used to predict biochemical reactions altered optimal for HIV-1 *** addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with ***:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host *** silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic *** vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,Ptegrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.

关键词： HIV-1 Flux balance analysis Genome-scale metabolic models Viral biomass objective function therapeutic target

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Influences of chemical reactions on polysulfide reduction reaction process on promotor surface in Li-S batteries

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Nano Research 2024年第4期17卷 2712-2718页

作者： Yufeng luo Zhenhan Fang Zixin Hong Shaorong Duan Haitao Liu Hengcai Wu Qunqing Li Yuegang Zhang Shoushan Fan Wenhui Duan Jiaping Wang tsinghua-Foxconn Nanotechnology Research Center Tsinghua UniversityBeijing 100084China Department of Physics Tsinghua UniversityBeijing 100084China Laboratory of Computational Physics Institute of Applied Physics and Computational MathematicsBeijing 100088China Frontier Science Center for Quantum Information Tsinghua UniversityBeijing 100084China

Polar promotors have been proven effective in catalyzing the polysulfide(PS)reduction reaction(PSRR)process in lithium-sulfur(Li-S)***,the promotor surface tends to be poisoned due to the accumulation of insoluble discharging products of lithium disulfide(Li_(2)S_(2))and lithium sulfide(Li_(2)S)during Li-S battery ***,we investigate the detailed PSRR mechanism on the surface of manganese sulfides(MnS)as a representative promoter by performing in-situ Raman mapping *** catalytic ability of MnS enables thorough electrochemical reduction of PSs to Li_(2)S_(2) and Li_(2)S on the MnS *** generated Li_(2)S_(2) and Li_(2)S then adsorb the dissolved PSs via chemical reactions among sulfur species during the subsequent PSRR *** phenomenon mitigates promotor poisoning and continuously improves the reversible ***,the assembled Li-S cell demonstrates excellent electrochemical performance after introducing a conductive interlayer containing a thin piece of carbon nanotube film and MnS promotors.

关键词： promotors polysulfides chemical reactions catalytic ability in-situ Raman measurements

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