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Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1441-1456页

作者： Xin Zhuo Yue Wu Xiujuan Fu Jianbin Li Yuxin Xiang Xiaoyu Liang Canquan Mao Yuhong Jiang Sichuan Engineering research center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue *** is an urgent need to explore potential drug strategies for mitigating lung ***-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal ***,it has been rarely reported about the role of PAR2 in lung *** study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in ***,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of *** also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS ***,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

关键词： Protease-activated receptor 2(PAR2) CRISPR-Cas9 Gene editing Inflammation Acute lung inflammation NLRP3 Nanoparticles Drug delivery

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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

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Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to ***,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD *** several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on *** this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different *** results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD ***,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological *** the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the ***,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild *** summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced *** models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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SsdchA is a novel secretory cellobiohydrolase driving pathogenicity in Sclerotinia sclerotiorum

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The Crop Journal 2024年第2期12卷 493-502页

作者： Yangui Chen Yijuan Ding Siqi Zhao Nan Yang Zhaohui Wu Ping Zhang Hongmei Liao Mengquan Dong Yang Yu Huafang Wan Wei Qian Integrative Science center of Germplasm Creation in Western China(Chongqing)Science City College of Agronomy and BiotechnologySouthwest UniversityChongqing 400715China Academy of Agricultural Sciences Southwest UniversityChongqing 400715China Engineering research center of South Upland Agriculture Ministry of EducationChongqing 400715China College of Plant Protection Southwest UniversityChongqing 400715China

The necrotrophic fungus, Sclerotinia sclerotiorum, employs an array of cell wall-degrading enzymes(CWDEs), including cellulase, to dismantle host cell walls. However, the molecular mechanisms through which S. sclerotiorum degrades cellulose remain elusive. Here, we unveil a novel secretory cellobiohydrolase, SsdchA, characterized by a signal peptide and a Glyco_hydro_7(GH7) domain. SsdchA exhibits a robust expression of during early infection stages. Interestingly, colony morphology and growth rates remain unaffected across the wild-type, SsdchA deletion strains and SsdchA overexpression strains on potato dextrose agar(PDA) medium. Nevertheless, the pathogenicity and cellobiohydrolase activity decreased in the SsdchA deletion strains, but enhanced in the SsdchA overexpression strains. Moreover,the heterologous expression of SsdchA in Arabidopsis thaliana leads to reduced cellulose content and heightened susceptibility to S. sclerotiorum. Collectively, our data underscore the pivotal role of the novel cellobiohydrolase SsdchA in the pathogenicity of S. sclerotiorum.

关键词： Cellobiohydrolase Cellulose Pathogenicity Sclerotinia sclerotiorum Secretory protein SsdchA

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Effects of conductive agent type on lithium extraction from salt lake brine with LiFePO_(4) electrodes

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International Journal of Minerals,Metallurgy and Materials 2024年第4期31卷 678-687页

作者： Zhen Zhang Pan Luo Yan Zhang Yuhan Wang Li Liao Bo Yu Mingshan Wang Junchen Chen Bingshu Guo Xing Li School of New Energy and Materials Southwest Petroleum UniversityChengdu 610500China Energy Storage research Institute Southwest Petroleum UniversityChengdu 610500China

Electrochemical lithium extraction from salt lakes is an effective strategy for obtaining lithium at a low ***,the elevated Mg:Li ratio and the presence of numerous coexisting ions in salt lake brines give rise to challenges,such as prolonged lithium extraction periods,diminished lithium extraction efficiency,and considerable environmental *** this work,Li FePO4(LFP)served as the electrode material for electrochemical lithium *** conductive network in the LFP electrode was optimized by adjusting the type of conductive *** approach resulted in high lithium extraction efficiency and extended cycle *** the single conductive agent of acetylene black(AB)or multiwalled carbon nanotubes(MWCNTs)was replaced with the mixed conductive agent of AB/MWCNTs,the average diffusion coefficient of Li+in the electrode increased from 2.35×10^(-9)or 1.77×10^(-9)to 4.21×10^(-9)cm^(2)·s^(-1).At the current density of 20 mA·g^(-1),the average lithium extraction capacity per gram of LFP electrode increased from 30.36 mg with the single conductive agent(AB)to 35.62 mg with the mixed conductive agent(AB/MWCNTs).When the mixed conductive agent was used,the capacity retention of the electrode after 30 cycles reached 82.9%,which was considerably higher than the capacity retention of 65.8%obtained when the single AB was ***,the electrode with mixed conductive agent of AB/MWCNTs provided good cycling *** the conductive agent content decreased or the loading capacity increased,the electrode containing the mixed conductive agent continued to show excellent electrochemical ***,a self-designed,highly efficient,continuous lithium extraction device was *** electrode utilizing the AB/MWCNT mixed conductive agent maintained excellent adsorption capacity and cycling performance in this *** work provides a new perspective for the electrochemical extraction of lithium using LFP electrodes.

关键词： salt lake brine lithium extraction electrochemical lithium extraction conductive agent extraction efficiency adsorption capacity

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Accelerated design of high-performance Mg-Mn-based magnesium alloys based on novel bayesian optimization

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Journal of Magnesium and Alloys 2024年第2期12卷 750-766页

作者： Xiaoxi Mi Lili Dai Xuerui Jing Jia She Bjørn Holmedal Aitao Tang Fusheng Pan College of Materials Science and Engineering Chongqing UniversityChongqing 400044China southwest Technology and Engineering research Institute Chongqing 400039China national Engineering research center for Magnesium Alloys Chongqing UniversityChongqing 400044China Department of Materials Science and Engineering Norwegian University of Science and Technology(NTNU)Trondheim 7051Norway

Magnesium(Mg),being the lightest structural metal,holds immense potential for widespread applications in various *** development of high-performance and cost-effective Mg alloys is crucial to further advancing their commercial *** the rapid advancement of machine learning(ML)technology in recent years,the“data-driven''approach for alloy design has provided new perspectives and opportunities for enhancing the performance of Mg *** paper introduces a novel regression-based Bayesian optimization active learning model(RBOALM)for the development of high-performance Mg-Mn-based wrought *** employs active learning to automatically explore optimal alloy compositions and process parameters within predefined ranges,facilitating the discovery of superior alloy *** model further integrates pre-established regression models as surrogate functions in Bayesian optimization,significantly enhancing the precision of the design *** RBOALM,several new high-performance alloys have been successfully designed and ***,after mechanical property testing of the designed alloys,the Mg-2.1Zn-2.0Mn-0.5Sn-0.1Ca alloy demonstrates exceptional mechanical properties,including an ultimate tensile strength of 406 MPa,a yield strength of 287 MPa,and a 23%fracture ***,the Mg-2.7Mn-0.5Al-0.1Ca alloy exhibits an ultimate tensile strength of 211 MPa,coupled with a remarkable 41%fracture elongation.

关键词： Mg-Mn-based alloys High-performance Alloy design Machine learning Bayesian optimization

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CFD Investigation of Diffusion Law and Harmful Boundary of Buried Natural Gas Pipeline in the Mountainous Environment

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Energy Engineering 2024年第8期121卷 2143-2165页

作者： Liqiong Chen Kui Zhao Kai Zhang Duo Xv Hongxvan Hu Guoguang Ma Wenwen Zhan School of Petroleum Engineering Southwest Petroleum UniversityChengdu610000China national Pipe Network Group southwest Pipeline Co. Ltd.Chengdu610000China national Pipeline research center Conveyance Pipe Institute Baoji Petroleum Steel Pipe Co.Ltd.Baoji721000China

The leakage gas from a buried natural gas pipelines has the great potential to cause economic losses and environmental pollution owing to the complexity of the mountainous *** this study,computational fluid dynamics(CFD)method was applied to investigate the diffusion law and hazard range of buried natural gas pipeline leakage in mountainous *** on cloud chart,concentration at the monitoring site and hazard range of lower explosion limit(LEL)and upper explosion limit(UEL),the influences of leakage hole direction and shape,soil property,burial depth,obstacle type on the diffusion law and hazard range are *** show that the leakage gas is not radially diffused until it reaches the ground,and the velocity of gas diffusion to the ground and the hazard range decrease as the angle between the leaking direction and the buoyancy direction *** and square leak holes have a faster diffusion rate and a wider hazard range than *** diffusion rate of leakage gas in soil rises as soil granularity and porosity *** time of leakage gas diffusion to the ground increases significantly with the increase of burial depth,and the hazard range reduces as burial depth ***-type obstacles will alter the diffusion path of the leakage gas and accelerate the expansion of the hazard distance,while trench-type obstacles will cause the natural gas to accumulate in the trench and form a high concentration region slowing the expansion of the surface gas concentration.

关键词： Mountainous environment buried pipeline leakage and diffusion hazard range numerical simulation

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

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Zoological research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State Key Laboratory of Genetic Evolution&Animal Models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China national Resource center for Non-Human primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Highly efficient expression of human extracellular superoxide dismutase(rhEcSOD)with ultraviolet-B-induced damage-resistance activity in transgenic silkworm cocoons

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Insect Science 2024年第4期31卷 1150-1164页

作者： Feng Wang Ri-Yuan Wang De-Bin Zhong Ping Zhao Qing-You Xia Integrative Science center of Germplasm Creation in Western China(CHONGQING)Science City Biological Science Research CenterSouthwest UniversityChongqingChina Century Legend Biotechnology research Institute(Chongqing)Co. Ltd.ChongqingChina

Extracellular superoxide dismutase(EcSOD)protects tissues from oxidative stress,and thus is considered as a therapeutic agent for many diseases such as atherosclerosis,hypertension,and ***,cost-effective production of bioactive recombinant human EcSOD(rhEcSOD)remains a ***,we developed an efficient strategy for producing active rhEcSOD by transgenic *** was successfully synthesized as homodimers and homotetramers in the middle silk gland and spun into the cocoons with a concentration of 9.48±0.21 mg/*** of rhEcSOD from the cocoons could be conveniently achieved with a purity of 99.50%and a yield of 3.5±0.5 mg/***,N-glycosylation at the only site of N89 in rhEcSOD with 10 types were *** purified rhEcSOD gained the potent enzymatic activity of 4162±293 U/mg after Cu/Zn ions *** importantly,rhEcSOD was capable of penetrating and accumulating in the nuclei of cells to maintain cell morphology and attenuate ultraviolet B-induced cell apoptosis by eliminating reactive oxygen species and inhibiting the C-Jun N-terminal kinase signaling *** results demonstrated that the transgenic silkworm could successfully produce rhEcSOD with enzymatic and biological activities for biomedical applications.

关键词： antioxidant human extracellular superoxide dismutase recombinant expression silkworm silk gland

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The Identification of Phenylalanine Ammonia-Lyase(PAL)Genes from Pinus yunnanensis and an Analysis of Enzyme Activity in vitro

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Phyton-International Journal of Experimental Botany 2024年第3期93卷 503-516页

作者： Dejin Mu Lin Chen Heze Wang Zhaoliu Hu Sihui Chen Shi Chen Nianhui Cai Yulan Xu Junrong Tang Key Laboratory of national Forestry and Grassland Administration on Biodiversity Conservation in southwest China Southwest Forestry UniversityKunming650224China College of Forestry Southwest Forestry UniversityKunming650224China

Phenylalanine ammonia lyase(PAL)is the rate-limiting and pivotal enzyme of the general phenylpropanoid path-way,but few reports have been found on PAL genes in Pinus *** the present study,three PAL genes were cloned and identiﬁed from *** seedlings for theﬁrst time,namely,PyPAL-1,PyPAL-2,and *** results indicated that the open-reading frames of PyPAL genes were 2184,2157,and 2385 *** tree analysis revealed that PyPALs have high homology with other known PAL genes in other *** vitro enzymatic analysis showed that all three PyPAL recombinant proteins could catalyze the deamination of L-phenylalanine to form trans-cinnamic acid,but only PAL1 and PAL2 can catalyze the conversion of L-tyrosine toρ-coumaric *** PyPAL genes were expressed in different tissues in 1-year-old ***,and such genes had different expression *** study lays a foundation for further understanding of the biosynthesis of secondary metabolites in ***.

关键词： Pinus yunnanensis phenylalanine ammonia-lyase enzyme activity in vitro functional analysis secondary metabolites

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Numerical Simulation of the Mechanical Stirring Process in a Tannin-Based Foaming Precursor Resin

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Fluid Dynamics & Materials Processing 2024年第10期20卷 2219-2234页

作者： Lan Huang Wenbin Yuan Hisham Essawy Xiaojian Zhou Xinyi Chen Yunnan Provincial Key Laboratory of Wood Adhesives and Glued Products Southwest Forestry UniversityKunming650224China Department of Polymers and Pigments National Research CentreCairo12622Egypt Key Laboratory for Forest Resources Conservation and Utilization in the southwest Mountains of China Southwest Forestry UniversityKunming650224China

Tannin foam is a new functional *** can be widely applied to the automobile industry,construction industry,and packaging industry due to its wide range of raw materials,renewable,easily degraded,low cost and almost no *** tannin foam is a very complex process that includes high temperature,two phases,mechanical agitation,and phase *** investigate the influence of the stirring velocity and paddle shape,simulation was calculated by making use of the volume of fluid(VOF)method and multiple reference frame(MRF)method in a three-dimensional flow field of tannin-based foaming precursor *** gas holdup and velocity magnitude were analysed with various conditions of mechanical velocities and paddle shape in the stirring flow *** result shows the higher the velocity,the greater the disturbance and paddle shape between the eggbeater and the Rushton turbine,obviously the paddle shape of the eggbeater with a wider range of agitation,which can entrap more air into the tannin-based foaming precursor resin in a short *** when the speed is 1500 rpm,the flow field of the Rushton turbine comes out of a ditch,which decreases the efficiency of mass transfer;there is less air to mix into the tannin-based foaming precursor resin,which causes *** the same time,the eggbeater shows the marvelous capability of hybrid as it has two vortexes and multiple cycles that make a difference from the Rushton turbine,which has only one vortex and two upper and lower loops;the structure makes the flow field more stable allowed evenness of flow field tannin-based foaming precursor *** results reveal that it is beneficial for tannin-based foaming precursor resin to use an eggbeater with a speed of 1500 rpm to reduce the consumption of resources while obtaining a uniform flow field.

关键词： Tannin-based foaming precursor resin mechanical agitation numerical simulation volume of fluid(VOF) multiple reference frame(MRF)

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