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GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice

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Current Medical Science 2022年第5期42卷 1046-1054页

作者： Wan-ran HUANG Jun-xue tu Ai-qing QIAO Li-jia CHEN Department of Pharmacy The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000China

Objective To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism.Methods The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide(LPS).The chondrocytes were divided into the control group,LPS group,LPS+50 nmol/L GW842166X group,and LPS+100 nmol/L GW842166X group.The cytotoxicity of GW842166X was tested using the CCK-8 assay.Western blot,RT-qPCR,and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes.The expression of extracellular matrix molecules was detected by the Western blot,RT-qPCR,and immunofluorescence.Additionally,the activity of NF-κB was checked by the Western blot and immunofluorescence.The mouse Hulth models were generated to examine the in vivo effects of GW842166X on osteoarthritis.Hematoxylin and eosin staining,safranin O/fast green staining,and immunohistochemistry were applied to detect the histological changes.Results GW842166X below 200µmol/L had no cytotoxicity on the mouse chondrocytes.LPS-induced high expression of TGF-β1,IL-10,TNF-α,and IL-6 was significantly reduced by GW842166X.In addition,GW842166X upregulated the expression of aggrecan and collagen type III,which was downregulated after the LPS stimulation.The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment.Furthermore,LPS decreased the IκBαexpression in the cytoplasm and increased the nuclear p65 expression.However,these changes were reversed by the GW842166X pretreatment.Moreover,the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X.Conclusion GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes,thereby inhibiting the progression of osteoarthritis.

关键词： GW842166X lipopolysaccharide osteoarthritis chondrocyte catabolism cartilage extracellular matrix

Controlling antifungal activity with light:Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

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药学学报:英文版 2023年第7期13卷 3080-3092页

作者： Zhuang Li Na Liu Wanzhen Yang Jie tu Yahui Huang Wei Wang Chunquan sheng State Key Laboratory of Bioengineering Reactor And Shanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science&TechnologyShanghai 200237China School of Pharmacy Second Military Medical University(Naval Medical University)Shanghai 200433China Department of Pharmacology and Toxicology College of PharmacyAnd BIO5 InstituteUniversity of ArizonaTucsonAZ 85721USA

Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

关键词： Antifungal agents Ergosterol biosynthesis Triazoles Photocaged Optical control

Cysteine-rich peptides: signals for pollen tube guidance, species isolation and beyond

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Science China(Life Sciences) 2019年第9期62卷 1243-1245页

作者： sheng Zhong Li-jia Qu State Key Laboratory for Protein and Plant Gene Research Peking-Tsinghua Center for Life Sciences at College of Life SciencesPeking UniversityBeijing 100871China The National Plant Gene Research Center (Beijing) Beijing 100101China

In flowering plants,the two sperm cells are passive cargo transported into the ovule by pollen tubes (Zhang et al.,2017).Therefore,the precise guidance of pollen tubes is critical for successful double fertilization (Dresselhaus and Franklin-Tong,2013).A series of male-female interactions are required to guarantee the spatiotemporal regulation of pollen tube guidance because during growth,pollen tubes continuously interact with different female tissues (Zhong et al.,2017;Zhong and Qu,2019).In the past two decades,there has been tremendous progress in elucidating the molecular mechanisms of pollen tube guidance regulation,mostly using Arabidopsis thaliana as a model system (Johnson et al.,2019).

关键词： double fertilization pollen tube model system

Engaging Yne-Allenes in Cycloaddition Reactions: Recent Developments

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Chinese Journal of Chemistry 2022年第10期40卷 1224-1242页

作者： jia-Yin Wang Wen-Juan Hao Shu-jiang tu Bo jiang School of Chemistry&Materials Science Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional MaterialsJiangsu Normal UniversityXuzhouJiangsu 221116China

Yne-allenes bearing both a C-C triple bond and an allene unit are a class of focal substrates in organic synthesis,in view of their structure diversity,.high reactivity and intermediate variety in the past years.Engaging yne-allenes in numerous annulation cascades provides efficient and direct accesses to elaborate functionalized polycyclic molecular architectures in a convergent manner.There are lots of types of catalytic chemical reactions such as intramolecular cyclizations,cycloisomerizations,intermolecular annulations,and bicyclizations as well as tricyclizations with the assistance of Lewis acids,Bronsted acids,bases,transition metals,and otherr c atalysts.This review provides an overview of the chemistry developed with transformations of yne-allenes by discussing their general and specific reactivities,presenting and commenting on their mechanisms as well as their applications.

关键词： Yne-alenes Cycloaddition Domino reactions Carbocycles Heterocycles

Forward Expansiveness and Entropies for Subsystems of Z+k-actions

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Acta Mathematica Sinica,English Series 2023年第4期39卷 633-662页

作者： Yao jia GUO Xin sheng WANG Yu Jun ZHU School of Mathematical Sciences Xiamen University

In this paper,forward expansiveness and entropies of "subsystems"2) of Z+k-actions are investigated.Let α be a Z+k-action on a compact metric space.For each 1 ≤j≤k-1,denote Gj+={V+:=V ∩R+k:V is a j-dimensional subspace of Rk}.We consider the forward expansiveness and entropies for α along V+∈ Gj+.Adapting the technique of "coding",which was introduced by M.Boyle and D.Lind to investigate expansive subdynamics of Zk-actions,to the Z+kcases,we show that the set Ej+(α) of forward expansive j-dimensional V+is open in Gj+.The topological entropy and measure-theoretic entropy of j-dimensional subsystems of α are both continuous in Ej+(α),and moreover,a variational principle relating them is obtained.For a 1-dimensional ray L ∈G1+,we relate the 1-dimensional subsystem of α along L to an i.***.d.random transformation.Applying the techniques of random dynamical systems we investigate the entropy theory of 1-dimensional subsystems.In particular,we propose the notion of preimage entropy(including topological and measure-theoretical versions) via the preimage structure of α along L.We show that the preimage entropy coincides with the classical entropy along any L ∈E1+(α) for topological and measure-theoretical versions respectively.Meanwhile,a formula relating the measure-theoretical directional preimage entropy and the folding entropy of the generators is obtained.

关键词： ℤ k + -action forward expansiveness j -dimensional subsystems entropy preimage entropy folding entropy variational principle random transformation 37A35 37B40

Radiofrequency in Facial Rejuvenation

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International Journal of Dermatology and Venereology 2022年第2期5卷 94-100页

作者： jia-Jie Lyu sheng-Xiu Liu Department of Dermatology the First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China.

Rhytides and striae are prominent clinical signs of skin aging.Photoaging,characterized by a thinning epidermis and a decrease in collagens,is the main form of skin aging.Delaying the aging process is a concerning issue for dermatologists.Radiofrequency(RF)is a non-ablative technology used for skin rejuvenation,body contouring,and weight reduction.The selective electro-thermolysis stimulates collagen contraction and neocollagenesis.Compared to traditional cosmetic treatment,it has the advantages of fewer side effects and short patient downtime.This review aims to summarize the efficacy and safety of different RF devices and the limitations during RF treatments.Combinations of RF and other cosmetic technologies are demonstrated.Results have been approving for the various uses of RF,including skin laxity and wrinkles smoothening.However,many studies use subjective ways of evaluation.Further studies are needed to determine the optimization of RF treatments for facial rejuvenation.

关键词： radiofrequency rejuvenation skin tightening noninvasive aging skin

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左卡尼汀胃漂浮缓释片的制备及体外评价

药学与临床研究 2012年第2期20卷 97-102页

作者：陈聪涂家生中国药科大学药剂教研室南京210009

目的:应用Box-behnken效应面法优化左卡尼汀胃漂浮缓释片处方,并评价其体外漂浮和释放特性。方法:以粉末直接压片法制备片剂。采用单因素法筛选出主要影响因素,即硬度、HPMC用量及碳酸氢钠用量,以漂浮性能和不同时间点释药性能为评价指... 详细信息

目的:应用Box-behnken效应面法优化左卡尼汀胃漂浮缓释片处方,并评价其体外漂浮和释放特性。方法:以粉末直接压片法制备片剂。采用单因素法筛选出主要影响因素,即硬度、HPMC用量及碳酸氢钠用量,以漂浮性能和不同时间点释药性能为评价指标,通过Box-behnken设计实验优化处方,对体外释药数据进行方程拟合,并结合扫描电子显微镜对溶出前后片剂表面形态的观察,探讨其释药机理。结果:优选处方为每片含HPMCK100M 29.7%,碳酸氢钠5.0%,十八烷醇15.0%,硬度为4 kg.mm-2。体外释药符合Makoid-Banakar模型,药物的释药机制为骨架溶蚀与药物扩散双重作用。结论:Box-behnken效应面法可用于左卡尼汀胃漂浮缓释片处方优化,且制备工艺简单,优化处方具漂浮缓释作用。

关键词：左卡尼汀胃漂浮缓释

Characterization and mitigation option of greenhouse gas emissions from lactating Holstein dairy cows in East China

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Journal of Animal Science and Biotechnology 2022年第6期13卷 1959-1972页

作者： Peng jia Yan tu Zhihao Liu Qi Lai Fadi Li Lifeng Dong Qiyu Diao State Key Laboratory of Grassland Agro-ecosystems Key Laboratory of Grassland Livestock Industry InnovationMinistry of Agriculture and Rural AffairsEngineering Research Center of Grassland IndustryMinistry of EducationCollege of Pastoral Agriculture Science and TechnologyLanzhou UniversityLanzhou 730020People’s Republic of China Institute of Feed Research Chinese Academy of Agricultural Sciences/Sino-US Joint Lab on Nutrition and Metabolism of RuminantBeijing 100081People’s Republic of China College of Animal Science and Technology Henan University of Science and TechnologyLuoyang 471003People’s Republic of China College of Animal and Veterinary Sciences Southwest Minzu UniversityChengdu 610041People’s Republic of China.

Background:This study investigated greenhouse gas(GHG)emission characteristics of lactating Holstein dairy cows in East China and provided a basis for formulating GHG emission reduction measures.GreenFeed system was used to measure the amount of methane(CH_(4))and carbon dioxide(CO_(2))emitted by the cows through respiration.Data from a commercial cow farm were used to observe the effects of parity,body weight,milk yield,and milk component yield on CH_(4) and CO_(2) emissions.Results:Mean herd responses throughout the study were as follows:111 cows completed all experimental processes,while 42 cows were rejected because they were sick or had not visited the GreenFeed system 20 times.On average,lactating days of cows was 138±19.04 d,metabolic weight was 136.5±9.5 kg,parity was 2.8±1.0,dry matter intake(DMI)was 23.1±2.6 kg/d,and milk yield was 38.1±6.9 kg/d.The GreenFeed system revealed that CH_(4) production(expressed in CO_(2) equivalent,CO_(2)-eq)was found to be 8304 g/d,CH_(4)_(CO_(2)−eq)/DMI was 359 g/kg,CH_(4)_(CO_(2)−eq)/energy-corrected milk(ECM)was 229.5 g/kg,total CO_(2) production(CH_(4) production plus CO_(2) production)was 19,201 g/d,total CO_(2)/DMI was 831 g/kg,and total CO_(2)/ECM was 531 g/kg.The parity and metabolic weight of cows had no significant effect on total CO_(2) emissions(P>0.05).Cows with high milk yield,milk fat yield,milk protein yield,and total milk solids yield produced more total CO_(2)(P<0.05),but their total CO_(2) production per kg of ECM was low(P<0.05).The total CO_(2)/ECM of the medium and high milk yield groups was 17%and 27%lower than that of the low milk yield group,respectively.Conclusions:The parity and body condition had no effect on total CO_(2) emissions,while the total CO_(2)/ECM was negatively correlated with milk yield,milk fat yield,milk protein yield,and total milk solids yield in lactating Holstein dairy cows.Measurement of total CO_(2) emissions of dairy cows in the Chinese production system will help establish regional or national GHG inventories and develop m

关键词： Enteric methane emissions GreenFeed system Holstein dairy cows Mitigation option Production performance

Experimental,Numerical,and Analytical Studies on the Bending of Mechanically Lined Pipe

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China Ocean Engineering 2024年第2期38卷 221-232页

作者： WEI Wen-bin YUAN Lin ZHOU jia-sheng LIU Zheng State Key Laboratory of Hydraulic Engineering Simulation and Safety Tianjin UniversityTianjin 300072China School of Civil Engineering Tianjin UniversityTianjin 300072China School of Mechanical Engineering Tianjin UniversityTianjin 300072China

Mechanically lined pipe(MLP)is often used for offshore oil and gas transport because of its low cost and corrosion resistance.During installation and operation,the pipe may undergo severe bending deformation,which causes the liner to separate from the outer pipe and buckles,affecting the stability of the whole line.In this paper,the buckling response of MLP subjected to bending is investigated to clarify its bending characteristics by employing both experiments,numerical simulation,as theoretical methods.Two types of MLPs were manufactured with GB 45 carbon steel(SLP)and Al 6061(ALP)used as the outer pipe material,respectively.The hydraulic expansion and bending experiments of small-scale MLPs are conducted.In addition to the ovalized shape of the cross-section for the SLP specimens,the copper liner was found to wrinkle on the compressive side.In contrast,the liner of ALP remains intact without developing any wrinkling and collapse mode.In addition,a dedicated numerical framework and theoretical models were also established.It was found both the manufacturing and bending responses of the MLP can be well reproduced,and the predicted maximum moment and critical curvatures are in good agreement with the experimental results.

关键词： lined pipe bending nonlinear ring theory buckling plasticity