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Chemical biology investigation of a triple-action,smart-decomposition antimicrobial booster based-combination therapy against“ESKAPE”pathogens

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Science China Chemistry 2024年第9期67卷 3071-3082页

作者： Min Wang Huangsheng Pu Yangfan Xu Chenxuan Wu Yuanxin Gu Qingyun Cai Guoxing Yin Peng Yin Chunhui Zhang Wing-Leung Wong Muyang Wan Yugang Bai Xinxin Feng State Key laboratory of Chem-/Bio-Sensing and Chemometrics Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biologyand School of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China College of biology Hunan UniversityChangsha 410082China College of Advanced Interdisciplinary Studies&Hunan Provincial Key laboratory of Novel Nano Optoelectronic Information Materials and Devices National University of Defense TechnologyChangsha 410073China Nanhu Laser laboratory National University of Defense TechnologyChangsha 410073China Key laboratory of Chemical biology and Traditional Chinese Medicine Research(Ministry of Education) College of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081China State Key laboratory of Chemical biology and Drug Discovery Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China Hunan Provincial Key laboratory of Anti-Resistance Microbial Drugs The Third Hospital of Changsha(The Affiliated Changsha Hospital of Hunan University)Changsha 410015China

The global antibiotic resistance crisis necessitates urgent *** innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic *** study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition ***1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme *** multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial ***,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione *** mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.

关键词： antimicrobial booster oligoamidine membrane disruption DNA targeting triggered degradation anti-resistance

GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

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Molecular Plant 2024年第1期17卷 199-213页

作者： Xiaoxiao Duan Yuanya Zhang Xiahe Huang Xiao Ma Hui Gao Yan Wang Zhen Xiao Chengcheng Huang Zhongshu Wang Bolong Li Wenqiang Yang Yingchun Wang State Key laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100049China Key laboratory of Photobiology Instute of BotanyChinese Academy of SciencesBejing 100093China

Protein phosphorylation regulates a variety of important cellular and physiological processes in ***-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal *** is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry *** this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)*** mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and *** method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate *** is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

关键词： plant phosphoproteomics phosphopeptides LC–MS Arabidopsis salt stress

Curation,nomenclature,and topological classification of receptor-like kinases from 528 plant species for novel domain discovery and functional inference

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Molecular Plant 2024年第4期17卷 658-671页

作者： Qian Liu Qiong Fu Yujie Yan Qian Jiang Longfei Mao Long Wang Feng Yu Heping Zheng State Key laboratory of Chemo/Biosensing and Chemometrics Hunan University College of BiologyChangshaHunan 410082China Bioinformatics Center Hunan University College of BiologyChangshaHunan 410082China

Receptor-like kinases(RLKs)are the most numerous signal transduction components in plants and play important roles in determining how different plants adapt to their ecological *** on RLKs has focused mainly on a small number of typical RLK members in a few model *** is an urgent need to study the composition,distribution,and evolution of RLKs at the holistic level to increase our understanding of how RLKs assist in the ecological adaptations of different plant *** this study,we collected the genome assemblies of 528 plant species and constructed an RLK *** this dataset,we identified and characterized 524948 RLK family *** member underwent systematic topological classification and was assigned a gene ID based on a unified nomenclature ***,we identified two novel extracellular domains in some RLKs,designated Xiao and *** analysis of the RLK family revealed that the RLCK-XVII and RLCK-XII-2 classes were present exclusively in dicots,suggesting that diversification of RLKs between monocots and dicots may have led to differences in downstream cytoplasmic *** also used an interaction proteome to help empower data mining for inference of new RLK functions from a global perspective,with the ultimate goal of understanding how RLKs shape the adaptation of different plants to the environments/*** assembled RLK dataset,together with annotations and analytical tools,forms an integrated foundation of multiomics data that is publicly accessible via the metaRLK web portal(http://***).

关键词： RLK RLCK domain signaling pathway receptor-protein interactions

Angiosperm-wide analysis of fruit and ovary evolution aided by a new nuclear phylogeny supports association of the same ovary type with both dry and fleshy fruits

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Journal of Integrative Plant biology 2024年第2期66卷 228-251页

作者： Yezi Xiang Taikui Zhang Yiyong Zhao Hongjin Dong Hongyi Chen Yi Hu Chien-Hsun Huang Jun Xiang Hong Ma State Key laboratory of Genetic Engineering Ministry of Education Key Laboratory of Biodiversity and Ecological EngineeringInstitute of Plant BiologyCenter of Evolutionary BiologySchool of Life SciencesFudan UniversityShanghai 200438China Department of biology Howard Hughes Medical InstituteDuke UniversityDurhamNC 27708USA Department of biology the Eberly College of Scienceand the Huck Institutes of the Life Sciencesthe Pennsylvania State UniversityUniversity ParkPA 16802USA Hubei Key laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization College of Biology and Agricultural ResourcesHuanggang Normal UniversityHuanggang 438000China

Fruit functions in seed protection and dispersal and belongs to many dry and fleshy types,yet their evolutionary pattern remains unclear in part due to uncertainties in the phylogenetic relationships among several orders and *** we used nuclear genes of 502 angiosperm species representing 231 families to reconstruct a well supported phylogeny,with resolved relationships for orders and families with previously uncertain *** this phylogeny as a framework,molecular dating supports a Triassic origin of the crown angiosperms,followed by the emergence of most orders in the Jurassic and Cretaceous and their rise to ecological dominance during the Cretaceous Terrestrial *** robust phylogeny allowed an examination of the evolutionary pattern of fruit and ovary types,revealing a trend of parallel carpel fusions during early diversifications in eudicots,monocots,and ***,taxa in the same order or family with the same ovary type can develop either dry or fleshy fruits with strong correlations between specific types of dry and fleshy fruits;such associations of ovary,dry and fleshy fruits define several ovaryfruit"modules"each found in multiple *** of the frequent modules has an ovary containing multiple ovules,capsules and berries,and another with an ovary having one or two ovules,achenes(or other single-seeded dry fruits)and *** new perspective of relationships among fruit types highlights the closeness of specific dry and fleshy fruit types,such as capsule and berry,that develop from the same ovary type and belong to the same module relative to dry and fleshy fruits of other modules(such as achenes and drupes).Further analyses of gene families containing known genes for ovary and fruit development identified phylogenetic nodes with multiple gene duplications,supporting a possible role of whole-genome duplications,in combination with climate changes and animal behaviors,in angiosperm fruit and ovary diversificat

关键词： angiosperm fruit evolution MADS-box molecular clock nuclear phylogeny ovary and fruit developmental genes

Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

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Chinese Journal of Chemistry 2024年第10期42卷 1175-1189页

作者： Guo-Feng Luo Wei-Hai Chen Xian-Zheng Zhang state Key laboratory of oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei KeyLaboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanHubei 430079China Key laboratoryof Biomedical Polymers of Ministry of Education&Departmentof Chemistry Wuhan UniversityWuhanHubei 430072China

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of *** barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration *** achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing *** these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were *** the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

关键词： Nanomedicine Tumor stroma Deep penetration Enhanced drug perfusion Cancer therapy Drug carriers Biomaterials Nanotechnology

Overexpression of auxin/indole-3-acetic acid gene MdIAA24 enhances Glomerella leaf spot resistance in apple(Malus domestica)

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Horticultural Plant Journal 2024年第1期10卷 15-24页

作者： Qian Wang Dong Huang Wenyan Tu Fengwang Ma Changhai Liu State Key laboratory of Crop Stress biology for Arid Areas/Shaanxi Key laboratory of Apple College of HorticultureNorthwest A&F UniversityYanglingShaanxi 712100China

Auxin is throughout the entire life process of plants and is involved in the crosstalk with other hormones,yet its role in apple disease resistance remains *** this study,we investigated the function of auxin/indole-3-acetic acid(IAA)gene Md IAA24 overexpression in enhancing apple resistance to Glomerella leaf spot(GLS)caused by Colletotrichum fructicola(Cf).Analysis revealed that,upon Cf infection,35S::Md IAA24 plants exhibited enhanced superoxide dismutase(SOD)and peroxidase(POD)activity,as well as a greater amount of glutathione(reduced form)and ascorbic acid accumulation,resulting in less H_(2)O_(2)and superoxide anion(O_(2)^(-))in apple ***,35S::Md IAA24 plants produced more protocatechuic acid,proanthocyanidins B1,proanthocyanidins B2 and chlorogenic acid when infected with *** Cf infection,35S::Md IAA24 plants presented lower levels of IAA and jasmonic acid(JA),but higher levels of salicylic acid(SA),along with the expression of related *** overexpression of Md IAA24 was observed to enhance the activity of chitinase andβ-1,3-glucanase in Cfinfected *** results indicated the ability of Md IAA24 to regulate the crosstalk between IAA,JA and SA,and to improve reactive oxygen species(ROS)scavenging and defense-related enzymes *** jointly contributed to GLS resistance in apple.

关键词： Apple MdIAA24 Glomerella leaf spot(GLS) Antioxidant capacity Auxin Salicylic acid Jasmonic acid

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

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Journal of Integrative Plant biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key laboratory of Molecular and Cellular biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis

Two viral proteins translated from one open reading frame target different layers of plant defense

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Plant Communications 2024年第4期5卷 177-193页

作者： Yuzhen Mei Tao Hu Yaqin Wang Rosa Lozano-Duran Xiuling Yang Xueping Zhou State Key laboratory of Rice biology Institute of BiotechnologyZhejiang UniversityHangzhouZhejiang 310058China State Key laboratory for biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Department of Plant Biochemistry Center for Plant Molecular Biology(ZMBP)Eberhard Karls University72076 TubingenGermany

Multilayered defense responses are activated upon pathogen *** utilize a number of strategies to maximize the coding capacity of their small genomes and produce viral proteins for infection,including suppression of host ***,we reveal translation leakage as one of these strategies:two viral effec-tors encoded by tomato golden mosaic virus,chloroplast-localized C4(cC4)and membrane-associated C4(mC4),are translated from two in-frame start codons and function cooperatively to suppress ***4 localizes in chloroplasts,to which it recruits NbPUB4 to induce ubiquitination of the outer membrane;as a result,this organelle is degraded,and chloroplast-mediated defenses are ***,chloroplast-localized cC4 induces the production of singlet oxygen(1O2),which in turn promotes translo-cation of the 1O2 sensor NbMBS1 from the cytosol to the nucleus,where it activates expression of the CERK1 ***,an antiviral effect exerted by CERK1 is countered by mC4,localized at the plasma ***4,like cC4,recruits NbPUB4 and promotes the ubiquitination and subsequent degradation of CERK1,suppressing membrane-based,receptor-like kinase-dependent ***,this translation leakage strategy seems to be conserved in multiple viral species and is related to host *** suggests that stacking of different cellular antiviral responses could be an effective way to abrogate viral infection and engineer sustainable resistance to major crop viral diseases in thefield.

关键词： geminivirus C4 PUB4 CERK1 subcellular localization antiviral defense

Enhancing wheat regeneration and genetic transformation through overexpression of TaLAX1

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Plant Communications 2024年第5期5卷 9-24页

作者： Yang Yu Haixia Yu Jing Peng Wang Jinsong Yao Yi Peng Wang Feng Li Zhang Shi Rong Wang Yajie Zhao Xiang Yu Zhao Xian Sheng Zhang Ying Hua Su State Key laboratory of Crop biology College of Life SciencesShandong Agricultural UniversityTai’anShandong 271018China

In the realm of genetically transformed crops,the process of plant regeneration holds utmost ***,the low regeneration efficiency of several wheat varieties currently restricts the use of genetic transformation for gene functional analysis and improved crop *** research explores overex-pression of TaLAX PANICLE1(TaLAX1),which markedly enhances regeneration efficiency,thereby boost-ing genetic transformation and genome editing in *** noteworthy is the substantial increase in regeneration efficiency of common wheat varieties previously regarded as recalcitrant to genetic *** study shows that increased expression of TaGROWTH-REGULATING FACTOR(TaGRF)genes,alongside that of their co-factor,TaGRF-INTERACTING FACTOR 1(TaGIF1),enhances cytokinin accumulation and auxin response,which may play pivotal roles in the improved regeneration and transfor-mation of TaLAX1-overexpressing wheat *** of TaLAX1 homologs also significantly in-creases the regeneration efficiency of maize and soybean,suggesting that both monocot and dicot crops can benefit from this *** shed light on a gene that enhances wheat genetic trans-formation and elucidate molecular mechanisms that potentially underlie wheat regeneration.

关键词： plant regeneration genetic transformation TaLAX1 TaGRF4–TaGIF1 cytokinin auxin wheat