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Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

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Chinese Journal of Natural Medicines 2024年第10期22卷 914-928页

作者： LI Yichen HUANG Liting LI Jilang LI Siyuan LV Jianzhen ZHONG Guoyue GAO Ming YANG Shilin HAN Shan HAO Wenhui Life Sciences Institute Guangxi Medical University College of Pharmacy Guangxi University of Chinese Medicine National Pharmaceutical Engineering center for Solid Preparation in Chinese Herbal.Medicine Jiangxi University of Traditional Chinese Medicine Xinjiang Key Laboratory of molecular biology for Endemic Diseases Department of Biochemistry and Molecular BiologySchool of Basic Medical Sciences Xinjiang Medical University

Acute lung injury（ALI） is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide（AG）, a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide（LPS）-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4（TLR4）/Kelch-like ECH-associated protein 1（Keap1）/Nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway. molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol-1), and these interactions were further corroborated by Cellular Thermal Shift Assay（CETSA） and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

关键词： Acute lung injury Andrographolide Ferroptosis Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2 Toll-like receptor 4

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Remote copper-catalyzed enantioselective substitution of yne-thiophene carbonates

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Science China Chemistry 2024年第4期67卷 1175-1180页

作者： Hao-Dong Qian Xiang Li Tingrui Yin Wei-Feng Qian Chunhui Zhao Cuiju Zhu Hao Xu CCNU-uOttawa Joint research Centre Key Laboratory of Pesticides&Chemical Biology of Ministry of EducationInternational Joint Research Center for Intelligent Biosensing Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan 430079China

Here,we describe a strategy for the copper-catalyzed asymmetric heteroarylation of yne-thiophene carbonates with indoles via remote *** key to the success of this strategy lies in the design of the alkynyl group at the ortho-position of the heterocycle thiophene,enabling the formation of a triarylmethane moiety via very remote ***,the concept of remote copper-catalyzed asymmetric transformation extends not only to yne-allylic esters but also to yne-aryl *** reaction readily provides a diverse array of chiral triarylmethanes with high efficiency,enantioselectivity,and excellent functional group ***,facile follow-up transformations underscore their potential utility in the synthesis of various enantioenriched building *** mechanistic studies support the plausibility of the remote substitution pathway.

关键词： remote substitution copper catalyst asymmetric catalysis triaryl methanes

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Chloroplast immunity: A cornerstone of plant defense

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molecular Plant 2024年第5期17卷 686-688页

作者： Jie Liu Pan Gong Ruobin Lu Rosa Lozano-Duran Xueping Zhou Fangfang Li State Key Laboratory for biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100081China State Key Laboratory of Rice biology Institute of BiotechnologyZhejiang UniversityHangzhouZhejiang 310058China Department of Plant biochemistry Centre for Plant Molecular Biology(ZMBP)Eberhard Karls UniversityTubingen 72076Germany

Increasing evidence supports the notion that pattern-recognition-receptor-mediated immunity goes beyond plasma membrane-to-nucleus *** the findings of the pathways linking plasma membrane and chloroplasts and the functions of stromules and perinuclear chloroplast clustering(PCC)in plant defense,chloroplast immunity has emerged as a cornerstone of plant defense and a target of plant pathogens.

关键词： plant immunity corners

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Application of plant DNA metabarcoding of lake sediments for monitoring vegetation compositions on the Tibetan Plateau

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Science China Earth Sciences 2024年第11期67卷 3594-3609页

作者： Kai WU Kai LI Weihan JIA Kathleen R.STOOF-LEICHSENRING Ulrike HERZSCHUH Jian NI Mengna LIAO Fang TIAN College of Life Sciences Zhejiang Normal University Polar Terrestrial Environmental Systems research Group Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research Institute of Environmental Science and Geography University of Potsdam Institute of biochemistry and biology University of Potsdam College of Resource Environment and Tourism Capital Normal University

Benefiting from the rapid development of environmental DNA(eDNA) technologies, sedimentary DNA(sedDNA)emerges as a promising tool for monitoring plant compositions in remote regions. The Tibetan Plateau(TP), renowned for its harsh environment and numerous ponds and lakes, presents a potentially demanding region for the application of sedDNA on vegetation investigations. Here, we used the g and h universal primers for the P6 loop region of the chloroplast trn L(UAA)intron to amplify plant DNA in surface sediments from 59 ponds and small lakes on the southwestern TP. The applicability and limitations of using plant DNA metabarcoding for modern vegetation monitoring and palaeo-vegetation reconstructions have been assessed by comparing sedDNA, pollen, and vegetation survey data. Our results showed that plant DNA metabarcoding recorded 186 terrestrial taxa, of which 30.1% can be identified at the species level. The plant sedDNA approach can effectively disclose the dominant plant taxa(including Asteraceae, Cyperaceae and Poaceae) and significant vegetation assemblages in the vicinity of the investigated sites. The number of taxa and taxonomic resolution of plant sedDNA exceeded that of pollen analysis(75 taxa detected, 5.3% can be identified at species level). Unlike pollen that retains a broad spectrum of regional plant signals(including Pinus and Artemisia), plant sedDNA mirrors very local plants, underscoring its utility in local vegetation monitoring and reconstructions. To conclude, plant DNA metabarcoding of(small) lake sediments warrant increased attention in the future for local vegetation monitoring and reconstructions on the TP.

关键词： Sedimentary DNA (sedDNA) Metabarcoding Pollen Vegetation composition Tibetan Plateau

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mRNA vaccine technology for infectious diseases and beyond

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Science China(Life Sciences) 2024年第10期67卷 2267-2270页

作者： Pei Hao Xiao Li Xuan Li Wu Zhong Key Laboratory of molecular Virology and Immunology Shanghai Institute of Immunity and InfectionChinese Academy of SciencesShanghai 200031China Changchun Veterinary research Institute Chinese Academy of Agricultural SciencesChangchun 130122China Key Laboratory of Synthetic biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China National Engineering research center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

The rise of mRNA vaccine technology Vaccines stand as one of the most significant medical advancements,playing a crucial role in the prevention of infectious diseases and the improvement of global *** triumph of smallpox vaccination stands as a towering achievement in the annals of healthcare,leading to the complete elimination of a oncedevastating disease and showcasing the efficacy of vaccination methods.

关键词： methods vaccination prevention

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Biotransformation of ethylene glycol by engineered Escherichia coli

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Synthetic and Systems Biotechnology 2024年第3期9卷 531-539页

作者： Wenlong Yan Xinhua Qi Zhibei Cao Mingdong Yao Mingzhu Ding Yingjin Yuan Frontiers Science center for Synthetic biology and Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Frontiers research Institute for Synthetic biology Tianjin UniversityTianjin300072China

There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution,with ethylene glycol(EG)being one of the main components recovered from this ***,finding ways to convert PET monomer EG into high-value products is crucial for effective PET waste *** this study,we successfully engineered Escherichia coli to utilize EG and produce glycolic acid(GA),expecting to facilitate the biological recycling of PET *** engineered ***,able to utilize 10 g/L EG to produce 1.38 g/L GA within 96 h,was initially ***,strategies based on overexpression of key enzymes and knock-out of the competing pathways are employed to enhance EG utilization along with GA *** engineered ***,characterized by the highest GA production titer and substrate conversion rate,was *** GA titer increased to 5.1 g/L with a yield of 0.75 g/g EG,which is the highest level in the shake flake *** level analysis and metabolomic analysis were then conducted,revealing that overexpression of key enzymes and knock-out of the competing pathways improved the metabolic flow in the EG *** improved metabolic flow also leads to accelerated synthesis and metabolism of amino acids.

关键词： PET biological recycling Ethylene glycol utilization Glycolic acid production Escherichia coli Synthetic biology Metabolomics analysis

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Structural disruption of melanin-like polymers with boosted UV protection

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Science China Chemistry 2024年第5期67卷 1653-1663页

作者： Zhen Yang Xianheng Wang Wanjie Bai Zikun Zou Haoxing Wu Yiwen Li Department of Radiology Huaxi MR Research CenterFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China

Manipulating the energy structure of materials represents an efficient way to regulate their light absorption behaviors. For example, constructing donor-acceptor(D-A) structures to increase the polarizability and reduce the energy bandgap of local molecules has been widely used in the field of organic photovoltaics with ordered structures. Remarkably, even in disordered and chaotic systems such as melanin-like polydopamine(PDA), visible and near-infrared light absorption can be significantly improved using this strategy. However, there has been a noticeable dearth of research on the ultraviolet(UV) light absorption regulation of bioinspired polymers with disordered and chaotic architectures by tailoring the D-A microstructures. In this study, a series of benzoheterocyclic molecules with strong electron-donating features screened by molecular simulation calculations were involved in disrupting the D-A structures within PDA. The destruction of D-A structures promoted the increase of the energy band gap and finally boosted the UV absorption of PDA. The resulting PDA nanoparticles with enhanced UV absorption were further employed to fabricate UV shielding composite films to protect the growth of plants from harmful UV radiation. This research may open up new avenues for structural disruption of bioinspired polymers for enhanced photoprotection applications.

关键词： melanin-like polymers polydopamine D-A structure UV absorption photoprotection

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Synthetic fungal melanin UV absorbers

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Science China Chemistry 2024年第9期67卷 3098-3110页

作者： Chao Wang Rong Zhang Jianhua Zhang Xueqian Zhang Hengjie Zhang Huan Cao Zhen Yang Yiwen Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China Department of Radiology Huaxi MR Research CenterFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

Agents with robust ultraviolet(UV)absorption capabilities play a vital role in safeguarding organisms and inorganic materials from UV ***,the synthetic procedures towards these UV absorbers are usually lengthy and complicated,accompanied by undesirable side reactions and the generation of toxic *** nature,allomelanin,a class of melanins variant found in melanized fungi near the Chernobyl nuclear power plant,plays crucial roles in the cell wall of melanized fungi,offering resistance to harsh external environments and promising UV resistance ***,allomelanin can be rapidly biosynthesized via the polymerization of 1,8-dihydroxynaphthalene in presence of enzymes in *** by this,we report here a green enzymatic polymerization strategy to efficiently and eco-friendly synthesize polydihydroxynaphthalene(PDHN)-based artificial allomelanin nanoparticles(NPs)with interesting *** calculations and experimental results demonstrated that the PDHN NPs exhibited excellent UVabsorption capacity,surpassing another widely used artificial melanin,polydopamine(PDA).Moreover,the light absorption mechanism of PDHN NPs was systematically elucidated for the first ***,the PDHN NPs were incorporated with polyvinyl alcohol(PVA)to create an anti-aging composite film with significantly enhanced UV shielding *** potential of these composite films in safeguarding plants from UV damage was meticulously ***,these PDHN NPs were first found to produce hydroxyl radicals(·OH)under UV irradiation,offering antibacterial properties that expand their potential applications.

关键词： melanin artificial allomelanin nanoparticles green synthesis UV absorption antibacterial

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Generation and characterization of nanobodies targeting GPCR

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Biophysics Reports 2024年第1期10卷 22-30页

作者： Shenglan Zhang Zhiran Fan Jianfeng Liu Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Cellular Signaling laboratory International Research Center for Sensory Biology and Technology of MOST Key Laboratory of Molecular Biophysics of MOE College of Life Science and Technology Huazhong University of Science and Technology

G protein-coupled receptors(GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH(variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in Escherichia coli(E. coli) and purified to characterize their binding potency.

关键词： Nanobody Single domain antibody Heavy chain-only antibody GPCR G protein-coupled receptor

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Synthesis of boron nitride nanorod and its performance as a metalfree catalyst for oxidative desulfurization of diesel fuel

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Chinese Journal of Chemical Engineering 2024年第4期68卷 120-132页

作者： Tanaz Ghanadi Gholamreza Moradi Alimorad Rashidi Catalyst research center Faculty of Chemical and Petroleum EngineeringRazi UniversityKermanshahIran Nanotechnology research center Research Institute of Petroleum Industry(RIPI)TehranIran

In order to reduce the sulfur compounds in diesel fuel,boron nitride(BN)has been used as a novel metal-free catalyst in the present *** nanocatalyst was synthesized via template-free approach followed by heating treatment at 900℃ in nitrogen atmosphere that the characteristics of the sample were identified by the X-ray diffraction,Fourier-transform infrared spectroscopy,Raman spectroscopy,field emission scanning electron microscopy,transmission electron microscopy,atomic force microscopy,and N2 adsorption-desorption *** results of structural and morphological analysis represented that BN has been successfully *** efficacy of the main operating parameters on the process was studied by using response surface methodology based on the Box-Behnken design *** prepared catalyst showed high efficiency in oxidative desulfurization of diesel fuel with initial sulfur content of 8040 mg·kg^(-1)*** statistical analysis,a significant quadratic model was obtained to predict the sulfur removal as a function of efficient *** maximum efficiency of 72.4%was achieved under optimized conditions at oxidant/sulfur molar ratio of 10.2,temperature of 71℃,reaction time of 113 min,and catalyst dosage of 0.36 ***,the reusability of the BN was studied,and the result showed little reduction in activity of the catalyst after 10 times ***,a plausible mechanism was proposed for oxidation of sulfur compounds on the surface of the *** present study shows that BN materials can be selected as promising metal-free catalysts for desulfurization process.

关键词： Desulfurization Boron nitride(BN)nanostructure Experimental design BoxeBehnken

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