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Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

Acta Pharmaceutica Sinica B 2024年第2期14卷 869-880页

作者： Yucheng Zhao Yuedong He Liangliang Han Libo Zhang Yuanzheng Xia Fucheng Yin Xiaobing Wang Deqing Zhao Sheng Xu Fei Qiao Yibei Xiao Lingyi Kong Department of Resources Science of Traditional Chinese Medicines School of Traditional Chinese Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China College of Bioscience and biotechnology Hunan Agricultural UniversityChangsha 410128China Jiangsu key {1. of Bioactive Natural Product Research and state key {1. of Natural Medicines Department of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China key {1. of Crop Gene Resources and Germplasm Enhancement in Southern China Ministry of AgricultureTropical Crops Genetic Resources InstituteChinese Academy of Tropical Agricultural SciencesHaikou 517317China Institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014China Department of Pharmacology School of Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Pyran-and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans,respectively,exhibiting diverse physiological and medical ***,the biosynthetic mechanisms for their core structures remain poorly *** we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in *** included three distinct *** prenyltransferases(PpPT1.3)responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors,and two novel CYP450 cyclases(PpDC and PpOC)crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran *** analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring *** possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific *** identified two possible acidic amino acids Glu303 in PpDC and Asp301.in PpOC as vital in the catalytic *** study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

关键词： Tetrahydropyrans Tetrahydrofurans Baldwin rules Coumarins CYP450cyclase

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Ultra-warm artificial aerogel fibers:a biomimetic material based on polar bear hair

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Chinese Journal of Natural Medicines 2024年第6期22卷 481-482页

作者： LI Yu LI Siwen state {1. laboratory of Natural Medicines Jiangsu Key Laboratory of Drug ScreeningDepartment of Biomedical EngineeringSchool of EngineeringChina Pharmaceutical UniversityNanjing 211198China

Aerogels are widely recognized as the premier thermal insulation materials due to their high porosity and exception-ally low thermal conductivity^([1.2]).Regrettably,their wide-spread application in thermal insulation textiles is signific-antly limited by their fragility and poor ***-though many aerogel fibers made with silica^([3]),graphene^([4,5]),carbon nanotube^([6]),titanium oxide^([7]),and cellulose^([8])have been prepared through various methods.

关键词： Aerogel fibers Biomimetic materials Green technologies

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Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy

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Chinese Journal of Natural Medicines 2024年第2期22卷 127-136页

作者： WANG Wei LIU Lijuan YANG Zhuo LU Chuanjian TU Pengfei ZHAO Ruizhi ZENG Kewu state {1. laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China state {1. laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510006China

Psoriasis,a prevalent inherited skin condition,involves an inflammatory response as a key pathogenic *** Optimized Yinxieling Formula(OYF),rooted in traditional Chinese medicine,is extensively utilized in clinical settings to treat *** previous studies have demonstrated OYF’s significant anti-inflammatory effects in psoriasis,its potential molecular targets and active components remain *** study aimed to unveil the anti-psoriasis molecular targets and active components of *** findings indicated that OYF extract markedly reduced the production of several inflammatory mediators,including IL-23,nitric oxide,TNF-α,and IL-1.,in LPS-induced RAW264.7 *** synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy,known as Target *** enriched target proteins were subsequently identified via LC-MS/MS,followed by bioinformatics analysis to map the psoriasis-associated pathway-gene *** identified a total of 76 potential target proteins,which were highly associated with mRNA transcription *** particular,pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF *** further utilized a target protein-based affinity capture strategy,combined with LC-MS and SPR analysis,to globally screen OYF’s active components,focusing on the mRNA transcription regulator,fused in sarcoma(FUS).This process led to the identification of umbelliferone,vanillic acid,protocatechuic acid,gentisic acid,and echinacoside as key compounds targeting FUS to inhibit IL-23 ***,we formulated a compound cocktail(CpdC),which significantly reduced psoriasis area and severity index(PASI)scores and the expressions of IL-23 and Ki67 in an imiquimod(IMQ)-induced psoriasis mouse ***,our study elucidates the primary molecular targets and active components of OYF,offeri

关键词： Psoriasis Optimized Yinxieling Formula(OYF) FUS protein Molecular targets Affinity-purified strategy

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Amphipathicity mediated endocytosis of mesoporous silica nanoparticles with tunable frameworks

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Nano Research 2024年第9期17卷 8350-8359页

作者： Runfeng Lin Tiancong Zhao Liang Chen Minchao Liu Hongyue Yu Ruicong Wang Minjia Yuan Xiaomin Li Dongyuan Zhao Department of Chemistry State Key Laboratory of Molecular Engineering of PolymersiChemShanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsFudan UniversityShanghai 200433China Shanghai Qiran biotechnology Co. Ltd.Shanghai 201702China

Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the ***,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell *** understanding of interaction of amphiphilic particle with cell membrane is still ***,by combining the dissipative particle dynamics(DPD)with the framework construction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the *** results confirm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1.palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of *** validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane *** obtained three kinds of MSNs show similar diameter(~1.0 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity *** phenyl-bridged MSN with a carbon content of 27.1.exhibits enhanced cellular uptake,consistent with the theoretical simulation *** work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.

关键词： mesoporous silica nanoparticles mesoporous organosilica endocytosis cell membrane amphipathicity

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Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1.activation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3543-3560页

作者： Lixin Zhao Yuguang Zhu Hua Tao Xiying Chen Feng Yin Yingyi Zhang Jianfeng Qin Yongyin Huang Bikun Cai Yonghao Lin Jiaxiang Wu Yu Zhang Lu Liang Ao Shen Xi-Yong Yu The Fifth Affiliated Hospital Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical PharmacologyNMPA&State Key LaboratorySchool of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Pulmonary fibrosis poses a significant health threat with very limited therapeutic options *** this study,we reported the enhanced expression of mesenchymal homobox 1.MEOX1.in pulmonary fibrosis patients,especially in their fibroblasts and endothelial cells,and confirmed MEOX1.as a central orchestrator in the activation of profibrotic *** high-throughput screening,we identified Ailanthone(AIL)from a natural compound library as the first small molecule capable of directly targeting and suppressing *** demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-b1.TGF-b1..In an animal model of bleomycin-induced pulmonary fibrosis,AIL effectively mitigated the fibrotic process and restored respiratory ***,AIL acted as a suppressor of MEOX1.by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1.thereby inhibiting MEOX1.expression and *** summary,our findings pinpointed MEOX1.as a cell-specific and clinically translatable target in ***,we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis,specifically through the suppression of JUN-dependent MEOX1.activation.

关键词： Ailanthone MEOX1 Pulmonary fibrosis JUN TGF-b1 High-throughput screening Natural product

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Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th1. axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu Qiang Xu Jianjun Zou Yang Sun Wenjie Guo state {1. laboratory of pharmaceutical biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of Clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu key {1. of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th1. differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th1. axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th1. Colitis Allosteric activator

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WRKY33 negatively regulates anthocyanin biosynthesis and cooperates with PHR1.to mediate acclimation to phosphate starvation

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Plant Communications 2024年第5期5卷 134-147页

作者： Han Tao Fei Gao Linying Li Yuqing He Xueying Zhang Mengyu Wang Jia Wei Yao Zhao Chi Zhang Qiaomei Wang Gaojie Hong state {1. laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Key Laboratory of Biotechnology in Plant Protection of the MOA of China and Zhejiang ProvinceInstitute of Virology and BiotechnologyZhejiang Academy of Agricultural SciencesHangzhou 310021China state {1. laboratory of Subtropical Silviculture Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese MedicineZhejiang A&F UniversityHangzhou 311300China Department of Horticulture College of Agriculture and BiotechnologyZhejiang UniversityKey Laboratory of Horticultural Plant GrowthDevelopment and Quality ImprovementMinistry of AgricultureHangzhouZhejiangChina Institute of Sericulture and Tea Zhejiang Academy of Agricultural SciencesHangzhou 310000China

Anthocyanin accumulation is acknowledged as a phenotypic indicator of phosphate(Pi)***,negative regulators of this process and their molecular mechanisms remain largely *** this study,we demonstrate that WRKY33 acts as a negative regulator of phosphorus-status-dependent anthocyanin ***33 regulates the expression of the gene encoding dihydroﬂavonol 4-reductase(DFR),a rate-limiting enzyme in anthocyanin production,both directly and ***33 binds directly to the DFR promoter to repress its expression and also interferes with the MBW complex through interacting with PAP1.to indirectly inﬂuence DFR transcriptional ***�Pi conditions,PHR1.interacts with WRKY33,and the protein level of WRKY33 decreases;the repression of DFR expression by WRKY33 is thus attenuated,leading to anthocyanin accumulation in *** genetic and biochemical assays suggest that PHR1.is also involved in regulating factors that affect WRKY33 protein *** together,ourfindings reveal that Pi starvation represses WRKY33,a repressor of anthocyanin biosynthesis,tofinely tune anthocyanin ***‘‘double-negative logic’’regulation of phosphorus-status-dependent anthocyanin biosynthesis is required for the mainte-nance of plant metabolic homeostasis during acclimation to Pi starvation.

关键词： WRKY33 phosphate signaling PHR1 Arabidopsis thaliana anthocyanins

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Recombination and repeat-induced point mutation landscapes reveal trade-offs between the sexual and asexual cycles of Magnaporthe oryzae

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Journal of Genetics and Genomics 2024年第7期51卷 723-734页

作者： Xifang Zong Yaxin Lou Mengshuang Xia Kunyang Zhao Jingxuan Chen Ju Huang Sihai Yang Long Wang state {1. laboratory of pharmaceutical biotechnology School of Life SciencesNanjing UniversityNanjingJiangsu 210000China state {1. laboratory for Crop Genetics and Germplasm Enhancement Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjingJiangsu 210000China Co-Innovation Center for Sustainable Forestry in Southern China Nanjing Forestry UniversityNanjingJiangsu 210000China

The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endanger many crops *** shows that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates ***,the pervasive clonal lineages of *** observed in natural fields contradict this expectation.A better understanding of the roles of recombination and the fungi-specific repeat-induced point mutation(RIP)in shaping its evolutionary trajectory is essential to bridge this knowledge *** we systematically investigate the RIP and recombination landscapes in *** using a whole genome sequencing data from 252 population samples and 92 cross *** data reveal that the RIP can robustly capture the population history of ***,and we provide accurate estimations of the recombination and RIP rates across different *** ***,our results highlight a parent-of-origin bias in both recombination and RIP rates,tightly associating with their sexual potential and variations of effector *** bias suggests a critical trade-off between generating novel allelic combinations in the sexual cycle to facilitate host-jumping and stimulating transposon-associated diversification of effectors in the asexual cycle to facilitate host *** findings provide unique insights into understanding the evolution of blast fungus.

关键词： Magnaporthe oryzae Crossover Repeat-induced point mutation(RiP) Effectors Sexual reproduction

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Heterogeneous expression of stearoyl-acyl carrier protein desaturase genes SAD1.and SAD2 from Linum usitatissimum enhances seed oleic acid accumulation and seedling cold and drought tolerance in Brassica napus

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Journal of Integrative Agriculture 2024年第6期23卷 1864-1878页

作者： Jianjun Wang Yanan Shao Xin Yang Chi Zhang Yuan Guo Zijin Liu Mingxun Chen state {1. laboratory of Crop Stress Biology for Arid Areas/National Yangling Agricultural biotechnology&Breeding Center/Shaanxi {1. laboratory of Crop Heterosis/College of Agronomy Northwest A&F UniversityYangling 712100China

Flax(Linum usitatissimum L.)is a versatile crop and its seeds are a major source of unsaturated fatty ***-acyl carrier protein desaturase(SAD)is a dehydrogenase enzyme that plays a key role in oleic acid biosynthesis as well as responses to biotic and abiotic ***,the function of SAD orthologs from *** has not been ***,we found that two LuSAD genes,LuSAD1.and LuSAD2,are present in the genome of *** cultivar‘Longya 1.’.Heterogeneous expression of either LuSAD1.or LuSAD2 in Arabidopsis thaliana resulted in higher contents of total fatty acids and oleic acid in the ***,ectopic expression of LuSAD2 in *** caused altered plant ***,the overexpression of either LuSAD1.or LuSAD2 in Brassica napus also resulted in increased contents of total fatty acids and oleic acid in the ***,we demonstrated that either LuSAD1.or LuSAD2 enhances seedling resistance to cold and drought stresses by improving antioxidant enzyme activity and nonenzymatic antioxidant levels,as well as reducing membrane *** findings not only broaden our knowledge of the LuSAD functions in plants,but also offer promising targets for improving the quantity and quality of oil,and the abiotic stress tolerance of oil-producing crops,through molecular manipulation.

关键词： LuSAD oleic acid cold tolerance drought tolerance Linum usitatissimum Brassica napus

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Zwitterionic ring-opening polymerization of macrocyclic ethyleneoxy-substituted carbonate:Access to cyclic PEG-like polycarbonate

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Chinese Chemical Letters 2024年第3期35卷 282-286页

作者： Jin Huang Jinwen Li Rui Yan Yuanyuan Qu Fengzhen Guo Lei Shen Can-liang Ma Jie Sun Zhenjiang Li Kai Guo state {1. laboratory of Materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjing 211816China Institute of Nanjing Advanced Biomaterials&Processing Equipment Lishui Economic Development ZoneNanjing 211299China

The innovation in polymer design to rival conventional polyethylene glycol(PEG)is an important approach to achieving a more sustainable ***,cyclic PEG-like polycarbonates having high molecular weight(4.4–49.5 kg/mol)were enabled through zwitterionic ring-opening polymerization(ZROP)of macrocyclic carbonates(MCs)mediated by N-heterocyclic carbene(NHC).The thermodynamic behavior of polymerization depends on the ring size of *** this process,the ZROP of 1.-membered MC was driven by the change of enthalpy(ΔH_(p))which differed from the ZROP of 1.-membered MC driven by the entropic change(ΔS_(p)).Cyclic polycarbonates depicted improved thermostability(T_(d5%)≥204℃)and higher glass transition temperatures(T_(g)>–40℃)in comparison to their linear analogues(T_(d5%)≤1.5℃,T_(g)~–50℃).In addition,the mechanism of ZROP of MC was addressed through computational study.A distinct mechanism of polymerization distinguishable from the well-known NHC-mediated ZROP of cyclic esters was revealed,where the zwitterion from nucleophilic addition to MC,*** intermediate,cannot be ring-opened probably due to the delocalization of negative charge on the carbonate group,but serves as an active center for the *** comparison to PEG,the attained polymer demonstrated comparable hydrophilic and biocompatible properties,as revealed by the results of contact angle and in vitro cytotoxicity studies,suggesting that cyclic polycarbonate hold the promise as the alternative of PEG.

关键词： Zwitterionic ring-opening polymerization Cyclic polycarbonate Macrocycles Tetrahedral intermediate NHC carbene

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