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Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers

Molecular Plant 2024年第9期17卷 1472-1483页

作者： Qi yao Rundong Shen yang Shao yifu Tian Peijin Han Xuening Zhang Jian-kang Zhu yuming Lu Shanghai Collaborative Innovation Center of Agri-Seeds Joint Center for Single-Cell BiologySchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Shanghai Center for Plant Stress Biology Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 201602China University of the Chinese Academy of Sciences BeijingChina College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China

Geneupregulation through genome editing is important for plant research and *** insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with ***,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene *** address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice *** in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript ***-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant *** approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic ***,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene ***,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.

关键词： genome editing short transcriptional enhancers gene upregulation crop breeding

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Low temperature-mediated repression and far-red light-mediated induction determine morning FLOWERING LOCUS T expression levels

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Journal of Integrative Plant Biology 2024年第1期66卷 103-120页

作者： Hayeon Kim Hye Won kang Dae yeon Hwang Nayoung Lee Akane Kubota Takato Imaizumi young Hun Song Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Korea Department of Biology Ajou UniversitySuwon 16499Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Graduate School of Science and Technology Nara Institute of Science and TechnologyIkomaNara 630‐0192Japan Department of Biology University of WashingtonSeattleWA 98195USA Institute of Agricultural Life Sciences Seoul National UniversitySeoul 08826Korea

In order to flower in the appropriate season,plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis(Arabidopsis thaliana)FLOWERING LOCUS T(FT).In Arabidopsis,FT messenger RNA levels peak in the morning and evening under natural long-day conditions(LDs).However,the regulatory mechanisms governing morning FT induction remain poorly *** morning FT peak is absent in typical laboratory LDs characterized by high red:far-red light(R:FR)ratios and constant ***,we demonstrate that ZEITLUPE(ZTL)interacts with the FT repressors TARGET OF EATs(TOEs),thereby repressing morning FT expression in natural *** LDs with simulated sunlight(R:FR=1.0)and daily temperature cycles,which are natural LD-mimicking environmental conditions,FT transcript levels in the ztl mutant were high specifically in the morning,a pattern that was mirrored in the toe1 toe2 double *** night-to-morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the ***-red light counteracted ZTL activity by decreasing its abundance(possibly via phytochrome A(phyA))while increasing GIGANTEA(GI)levels and negatively affecting the formation of the ZTL-GI complex in the ***,the phyA-mediated high-irradiance response and GI play pivotal roles in morning FT *** findings suggest that the delicate balance between low temperature-mediated ZTL activity and the far-red light-mediated functions of phyA and GI offers plants flexibility in fine-tuning their flowering time by controlling FT expression in the morning.

关键词： far-red light FLOWERING LOCUS T flowering time GIGANTEA low night-to-morning temperature natural long days phytochrome A red to far-red ratio ZEITLUPE

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Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik De Clercq Christophe Pannecouque Dongwei kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CyP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

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Emergingγ-soft-like spectrum in^(196)Pt in the SU3-IBM(Ⅰ)

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Chinese Physics C 2024年第9期48卷 150-163页

作者： Tao Wang Bing-Cheng He Chun-Xiao Zhou Dong-kang Li Lorenzo Fortunato College of Physics Tonghua Normal UniversityTonghua 134000China Physics Division Argonne National LaboratoryLemontIllinois 60439USA College of Mathematics and Physics Science Hunan University of Arts and ScienceChangde 415000China Dipartimento di Fisica e Astronomia"G.Galilei"-Universitàdi Padova via Marzolo 8I-35131 PadovaItaly INFN-Sez.di Padova via Marzolo 8I-35131 PadovaItaly

Recently,studies have argued that a spherical-like spectrum emerges in the SU3-IBM,thus creating new approaches to understanding y-softness in realistic *** a previous study,γ-softness with degeneracy of the ground and quasi-y bands was *** this paper,another special point connected to the middle degenerate point is *** is found to be related to the properties of^(196)*** emergentγ-softness is also shown to be important for understanding the prolate-oblate asymmetric shape phase *** low-lying spectra,B(E2)values,and quadrupole moments in^(196)Pt are discussed,and we show that the new model can account for several observed *** is the first part of the discussion on theγ-soft-like spectrum of^(196)Pt.

关键词： SU3-IBM ^(196)Pt γ-soft-like spectrum

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Improved genome annotation of Brassica oleracea highlights the importance of alternative splicing

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Horticultural Plant Journal 2024年第4期10卷 961-970页

作者： yinqing yang Lei Zhang Qi Tang Lingkui Zhang Xing Li Shumin Chen kang Zhang ying Li Xilin Hou Feng Cheng State Key Laboratory of Crop Genetics and Germplasm Enhancement College of HorticultureNanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Vegetable Biobreeding Institute of Vegetables and FlowersChinese Academy of Agricultural SciencesKey Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture and Rural AffairsSino-Dutch Joint Laboratory of Horticultural GenomicsBeijing 100081China

Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so *** genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of ***,has been widely used as a common reference in biological *** its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 ***,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold ***,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS ***,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.

关键词： Brassica oleracea Oxford nanopore technologies Gene annotation Alternative splicing

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Ionizing terahertz waves with 260 MV/cm from scalable optical rectification

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Light(Science & Applications) 2024年第6期13卷 1075-1087页

作者： Hyeongmun Kim Chul kang Dogeun Jang yulan Roh Sang Hwa Lee Joong Wook Lee Jae Hee Sung Seong Ku Lee Ki-yong Kim Advanced Photonics Research Institute GISTGwangju61005Korea Department of Physics and Optoelectronics Convergence Research Center Chonnam National UniversityGwangju61186Korea Pohang Accelerator Laboratory POSTECHPohang37673Korea Center for Relativistic Laser Science Institute for Basic ScienceGwangju61005Korea Institute for Research in Electronics and Applied Physics Department of PhysicsUniversity of MarylandCollege ParkMaryland20742USA

Terahertz(THz)waves,known as non-ionizing radiation owing to their low photon energies,can actually ionize atoms and molecules when a sufficiently large number of THz photons are concentrated in time and ***,we demonstrate the generation of ionizing,multicycle,15-THz waves emitted from large-area lithium niobate crystals via phase-matched optical rectification of 150-terawatt laser pulses.A complete characterization of the generated THz waves in energy,pulse duration,and focal spot size shows that the field strength can reach up to 260 megavolts per *** particular,a single-shot THz interferometer is employed to measure the THz pulse duration and spectrum with complementary numerical *** intense THz pulses are irradiated onto various solid targets to demonstrate THz-induced tunneling ionization and plasma *** study also discusses the potential of nonperturbative THz-driven ionization in gases,which will open up new opportunities,including nonlinear and relativistic THz physics in plasma.

关键词： optical interferometer matched

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Targeted G-to-T base editing for generation of novel herbicide-resistance gene alleles in rice

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Journal of Integrative Plant Biology 2024年第6期66卷 1048-1051页

作者： yifu Tian Xinbo Li Jiyong Xie Zai Zheng Rundong Shen Xuesong Cao Mugui Wang Chao Dong Jian-kang Zhu Ministry of Agriculture and Rural Affairs Key Laboratory of Gene Editing Technologies(Hainan) Institute of Crop Sciences and National Nanfan Research InstituteChinese Academy of Agricultural SciencesSanya 572024China Hainan Seed Industry Laboratory Sanya 572024China Shanghai Center for Plant Stress Biology CAS Center for Excellence in Molecular Plant SciencesThe Chinese Academy of SciencesShanghai 201602China University of Chinese Academy of Sciences Beijing 100049China Institute of Advanced Biotechnology and School of MedicineSouthern University of Science and TechnologyShenzhen 518055China

Deaminase-based cytosine base editors(CBEs)and adenine base editors(ABEs)induce C-to-T and A-to-G transitions,respectively,enabling single-nucleotide variants(SNVs)in plants for research and crop enhancement(Li et al.,2023a).The C-to-G base editors(CGBEs)and A-to-y base editors(AyBEs),developed by incorporating glycosylases with CBEs and ABEs,expand the repertoire of base editing products,allowing C-to-T/G and A-to-T/G transversions in plants(Li et al.,2023b,2023c;Sretenovic et a.,2021).

关键词： base alleles CBE

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Research progress on rolling superlubricity in solid lubricants

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Science China(Technological Sciences) 2024年第7期67卷 1980-1990页

作者： LI PanPan LI HongXuan ZHU DongXiang ZHU yongQi kang Fuyan WANG Wan ZHANG yaXin LIU XiaoHong JI Li ZHOU HuiDi CHEN JianMin State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China School of Chemical Engineering Northwest Minzu UniversityLanzhou 730030China

Superlubricity is an ideal lubrication state where friction nearly vanishes between contact interfaces. It has become one of the most important research topics and approaches owing to its significance in reducing energy consumption and preventing device failures. As an efficient and universal lubricating principle capable of achieving superlubricity, rolling lubrication has attracted widespread attention in recent years. In this review, the theoretical concept of rolling lubrication and the experimental research progress of spherical/scroll structures are summarized. The review focuses on the possibility of achieving rolling lubrication using spherical/scroll structures(such as spherical fullerenes, carbon nanotubes, and formed and constructed spherical/scroll structures). The challenges in achieving rolling lubrication are summarized, and the possibility of molecular rolling lubrication,as well as its potential applications in superlubrication, are discussed.

关键词： spherical/scroll structure rolling lubrication superlubricity fullerene

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A_(2)B_(7)-type La-Mg-Ni alloys prepared by Mg thermal diffusion for improved hydrogen storage performance

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Rare Metals 2024年第7期43卷 3260-3272页

作者： yong-Xi Zhang Guan-Jiu Wu Jing Gu Hong-Xing kang.y.an Li Di Zhou Wen-Feng Wang Lu Zhang Shu-Min Han Hebei Key Laboratory of Applied Chemistry School of Environmental and Chemical EngineeringYanshan UniversityQinhuangdao 066004China Department of Chemistry and Biochemistry San Diego State UniversitySan DiegoCA92182-1030USA State Key Laboratory of Metastable Materials Science and Technology Yanshan UniversityQinhuangdao 066004China

A novel approach based on thermal diffusion was used to achieve controllable Mg content in A_(2)B_(7)-type La-Mg-Ni-based *** formation mechanism of the A_(2)B_(7)-type phase as a result of the thermal diffusion process and the effect of Mg content on hydrogen storage performance were investigated.X-ray diffraction(XRD)patterns and Rietveld refinement results showed that increased Mg transformed the LaNi_(5)phase in the La_(0.74)Sm_(0.03)y_(0.23)Ni_(4.32)Al_(0.04)precursor alloy into a superlattice *** electron microscopy(SEM)images showed that Mg was evenly distributed in the alloy *** in the superlattice significantly inhibited the phase decomposition of the superlattice structure during the hydrogen absorption/desorption *** A_(2)B_(7)-type La_(0.57)Sm_(0.02)y_(0.18)Mg_(0.23)Ni_(3.38)Al_(0.03)alloy composed of Gd_(2)Co_(7)and Ce_(2)Ni_(7)phases was successfully *** pressure-composition isotherm profiles showed that the alloy had a hydrogen storage capacity as high as 1.73 wt%,with good cycling *** 50 cycles of hydrogen absorption/desorption,the alloy retained a hydrogen storage capacity of 1.45 wt%,with a capacity retention rate of up to 84.28%.The Mg thermal diffusion process thus provides a new approach for the controlled preparation of La-Mg-Ni-based alloys.

关键词： La-Mg-Ni-based hydrogen storage alloy A_(2)B_(7)-type superlattice alloy Mg thermal diffusion process Phase transformation Hydrogen storage property

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Effects of axylitol-casein complex on insulin resistance and gut microbiota composition in high-fat-diet+streptozotocin-induced type 2 diabetes mellitus mice

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Food Science and Human Wellness 2024年第5期13卷 2741-2753页

作者： Fanhua Kong Juan Zhang Shimo kang Xinyu Shen Aicheng Liu yan Zheng Junhua Shao Xiqing yue College of Food Science Shenyang Agriculture UniversityShenyang 110866China

This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and ***-fat-diet(HFD)+streptozotocin(STZ)-induced T2DM mice were treated with xylitol(Xy),casein(CN),and XC,after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate *** decreased body weight and improved glucose tolerance,insulin sensitivity,pancreas impairment,blood lipid levels,and liver function in T2DM mice compared to Xy-and CN-treated ***,XC modulated theα-diversity,β-diversity and gut microbiota *** on Spearman’s correlation analysis,the relative abundances of Alistipes,Bacteroides,and Faecalibaculum were positively correlated and those of Akkermansia,Lactobacillus,Bifidobacterium,and Turicibacter were negatively correlated with the phenotypes related to the improvement of *** conclusion,we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM *** results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and,eventually,human trials.

关键词： Xylitol-casein complex Type 2 diabetes mellitus Insulin resistance Gut microbiota

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