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Restoring cellular calcium homeostasis to rescue ER stress by 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid acetoxymethyl ester-loaded lipid-mPLGA hybrid-nanoparticles for acute kidney injury therapy

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Chinese Chemical Letters 2024年第3期35卷 337-345页

作者： Jingwen Zhang Jiahui Yan Yanan Wang Hong liu xueping Sun Yuchao Gu Liangmin Yu Changcheng Li Jun Wu Zhiyu He Frontiers Science Center for Deep Ocean Multispheres and Earth System and Key Laboratory of Marine Chemistry Theory and TechnologyMinistry of EducationOcean University of ChinaQingdao 266100China College of Chemistry and Chemical Engineering Ocean University of ChinaQingdao 266100China School of Medicine and Pharmacy Ocean University of ChinaQingdao 266003China Sanya Oceanographic Institution Ocean University of ChinaQingdao 572024China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)NanshaGuangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong Kong 999077China

Early pathogenesis of ischemia-reperfusion(I/R)-induced acute kidney injury(AKI)is dominated by intracellular calcium overload,which induces oxidative stress,intracellular energy metabolism disorder,inflammatory activation,and a series of pathologic cascaded reactions that are closely intertwined with self-amplifying and interactive feedback loops,ultimately resulting in cell damage and kidney failure.Currently,most nanomedicines originate from the perspective of antioxidant stress,which can only quench existing reactive oxide species(ROS)but cannot prevent the continuous production of ROS,resulting in insufficient efficacy.As a safe and promising drug,BAPTA-AM is hydrolyzed into BAPTA by intracellular esterase upon entering cells,which can rapidly chelate with overloaded Ca^(2+),restoring intracellular calcium homeostasis,thus inhibiting ROS regeneration at the source.Here,we designed a KTP-targeting peptide-modified yolk-shell structure of liposome–poly(ethylene glycol)methyl ether-block-poly(L-lactide-co-glycolic)(mPLGA)hybrid nanoparticles(<100 nm),with the characteristics of high encapsulation rate,high colloid stability,facile modification,and prolonged blood circulation time.Once the BA/mPLGA@Lipo-KTP was targeted to the site of kidney injury,the cholesteryl hemisuccinate(CHEMS)in the phospholipid bilayer,as an acidic cholesterol ester,was protonated in the simulated inflammatory slightly acidic environment(pH 6.5),causing the liposomes to rupture and release the BA/mPLGA nanoparticles,which were then depolymerized by intracellular esterase.The BAPTA-AM was diffused and hydrolyzed to produce BAPTA,which can rapidly cut off the malignant loop of calcium overload/ROS generation at its source,blocking the endoplasmic reticulum(ER)apoptosis pathway(ATF4–CHOP–Bax/Bcl-2,Casp-12–Casp-3)and the inflammatory pathway(TNF-α–NF-κB–IL-6 axes),thus alleviating pathological changes in kidney tissue,thereby inhibiting the expression of renal tubular marker kidney injury molecule 1(Kim-1)(reduced by 82.9%)and also exhibiti

关键词： BAPTA-AM Calcium overload Acid-responsive AKI ER stress

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang xueping Wang Kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

Plant virology in the 21st century in China:Recent advances and future directions

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Journal of Integrative Plant Biology 2024年第3期66卷 579-622页

作者： Jianguo Wu Yongliang Zhang Fangfang Li Xiaoming Zhang Jian Ye Taiyun Wei Zhenghe Li Xiaorong Tao Feng Cui Xianbing Wang Lili Zhang Fei Yan Shifang Li Yule liu Dawei Li xueping Zhou Yi Li State Key Laboratory for Ecological Pest Control of Fujian and Taiwan Crops Vector-borne Virus Research CenterCollege of Plant ProtectionFujian Agriculture and Forestry UniversityFuzhou 350002China State Key Laboratory of Plant Environmental Resilience and Ministry of Agriculture Key Laboratory of Soil Microbiology College of Biological SciencesChina Agricultural UniversityBeijing 100193China State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Plant Genomics Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Rice Biology Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Department of Plant Pathology The Key Laboratory of Plant ImmunityNanjing Agricultural UniversityNanjing 210095China State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Plant VirologyNingbo UniversityNingbo 315211China MOE Key Laboratory of Bioinformatics Center for Plant BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China

Plant viruses are a group of intracellular pathogens that persistently threaten global food security.Significant advances in plant virology have been achieved by Chinese scientists over the last 20 years,including basic research and technologies for preventing and controlling plant viral diseases.Here,we review these milestones and advances,including the identification of new crop-infecting viruses,dissection of pathogenic mechanisms of multiple viruses,examination of multilayered interactions among viruses,their host plants,and virus-transmitting arthropod vectors,and in-depth interrogation of plantencoded resistance and susceptibility determinants.Notably,various plant virus-based vectors have also been successfully developed for gene function studies and target gene expression in plants.We also recommend future plant virology studies in China.

关键词： China emerging plant viruses plant virology plant resistance/susceptibility to viral infection plant-virus transmission vector interactions plant virus-based vectors viral pathogenesis

A Novel Method for the Quantitative Detection of Sericin Content in Silk Fiber Based on the Ratio of Aspartate to Alanine

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Journal of Renewable Materials 2023年第1期11卷 167-184页

作者： Yanfei Feng Jiaming Lin Longxing Niu Peng Pan xueping liu Linling Huang Ying Guo Mingzhong Li National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhou215123China

The development of a method for the quantitative determination of the sericin content ratio(SCR)is urgently needed for silk refining and the purification of silk fibroin for biomedical applications.In this work,a series of sericin/fibroin mixed samples with known SCRs were prepared by mixing initial samples of extracted sericin and fibroin from Bombyx mori silk.Significant differences were found in the contents of characteristic hydrophilic amino acids abundant in sericin and hydrophobic amino acids abundant in fibroin,and several linear relation-ships of SCR associated with the content ratios of Ser/Ala,Asp/Ala,Lys/Ala,Asp/Gly and Ser/Gly were estab-lished by amino acid analysis.Subsequently,the linear equation expressing SCR(%)as a function of the Asp to Ala content ratio X(%)was established as SCR=2.5634X−12.5587(R 2=0.9972).The results indicated that the SCR of degummed silks calculated by the equation is more objective and effective than the results obtained by the traditional weight loss method.Our study provides a novel approach for the sensitive and quantitative detection of the sericin content within the detection limit in unknown silks,which can contribute to quality control in the silk production process.

关键词： Silk sericin content amino acid analysis

Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan xueping Wang Zeyu liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

Study on Coconut Shell Activated Carbon Temperature Swing Adsorption of Benzene and Formaldehyde

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Journal of Renewable Materials 2022年第12期10卷 3573-3585页

作者： Zhiguang Yang Gaojun Yan xueping liu Zhengyuan Feng Xinfeng Zhu Yanli Mao Songtao Chen Zhisheng Yu Ruimei Fan Linlin Shan Henan Province Key Laboratory of Water Pollution Control and Rehabilitation Technology Henan University of Urban ConstructionPingdingshan467036China College of Resources and Environment University of Chinese Academy of SciencesBeijing100085China College of Basic Medical Sciences Xinxiang Medical UniversityXinxiang 453003China

Adsorption can be used to recover effectively the volatile organic gases(VOCs)in the exhaust gas from factories through using an appropriate adsorption bed.Due to form a physical or chemical bond,adsorption occurs between the porous solid medium and the liquid or gas multi component fluid mixture.The regeneration capa-city of the adsorbent is as important as the adsorption capacity and it determines the economics of the adsorption system.The regeneration of adsorbent can be realized through changing the pressure or temperature of the system.Here,activated carbon samples from coconut shell were prepared and characterized.Benzene or formal-dehyde in the mixed air was used as the adsorption object,and the adsorption experiment was carried out in a U-shaped bed.Discussed how adsorption was affected by activated carbon type,adsorbate and temperature.The results show that oxidation modifed activated carbon can increase the adsorption effect of form aldehyde,but will reduce the ad sorption effect of benzene,because their ad sorption mechanism is different.At 30℃,the saturated adsorption apacity of AC-0 for benzene is 437.0 mg/g.and that of AC-1 for formaldehyde is 670.5 mg/g.In the experimental range,it is found that the adsorption capacity increases with the decrease of temperature,and their changes are very consistent with the ftted ExpDecay1 function.

关键词： Activated carbon adsorption benzene formaldehyde oxidation modification

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改进头脑风暴优化算法求解多模态多目标问题

华中科技大学学报(自然科学版) 2024年第6期52卷 24-31页

作者：程适刘悦王雪萍靳红林陕西师范大学计算机科学学院

针对多模态多目标优化中存在的所得等价解数量不足和决策空间多样性维护难的问题，提出了一种基于分区搜索和非支配特殊拥挤距离排序的差分头脑风暴优化算法．在算法中分区搜索将决策空间划分为多个子空间以降低搜索难度并维持种群多样... 详细信息

针对多模态多目标优化中存在的所得等价解数量不足和决策空间多样性维护难的问题，提出了一种基于分区搜索和非支配特殊拥挤距离排序的差分头脑风暴优化算法．在算法中分区搜索将决策空间划分为多个子空间以降低搜索难度并维持种群多样性，k-均值聚类可以定位并维持多个帕累托最优解，非支配特殊拥挤距离排序可以同时考虑决策空间和目标空间的多样性，作为环境选择算子筛选解；将差分变异算子替代传统头脑风暴优化算法新个体生成算子以增强种群的多样性，帮助定位多个等价最优解．将该算法与其他5种智能算法在13个多模态多目标测试函数上进行实验，实验结果表明：基于分区搜索和非支配特殊拥挤距离排序的差分头脑风暴优化算法在11个测试函数上的性能优于其他5个算法，该优化算法能够尽可能多地在决策空间中找到多个等价帕累托最优解集，并且能保证在目标空间中具有良好的帕累托前沿分布．

关键词：多模态多目标优化头脑风暴优化算法多目标优化多模态优化群体智能

Free fatty acid receptor 2 promotes cardiomyocyte hypertrophy by activating STAT3 and GATA4

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Food Science and Human Wellness 2022年第2期11卷 405-417页

作者： Hui Gao Kunming Tian Xiaojun Feng Mengqing Yan Chen Gao Yisheng Jiang Chenhao Zhu Huzhe Zhu xueping liu Yingfu Peng Department of Pharmacology School of MedicineShaoxing UniversityShaoxing 312000China Department of Pharmacology School of MedicineJishou UniversityJishou 416000China Department of Environmental Toxicity Zunyi Medical UniversityZunyi 563006China The First Affi liated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230002China Department of Pharmacology School of MedicineGuangXi University of science and TechnologyLiuzhou 545006China

Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body.Free fatty acid receptor 2(FFA2)can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation.Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy,we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy.This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro.FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro,which was further strengthened by FFA2 overexpression,suggesting that FFA2 might contribute to cardiomyocyte hypertrophy.Furthermore,4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3,which were inhibited by an ERK1/2 inhibitor,and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB.Taken together,these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2,providing a potential new target for therapy.

关键词： FFA2 Cardiac hypertrophy GATA4 STAT3 ERK1/2

Pricing European Options Based on a Logarithmic Truncated t-Distribution

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Journal of Applied Mathematics and Physics 2023年第5期11卷 1349-1358页

作者： Yingying Cao xueping liu Yiqian Zhao Xuege Han School of Mathematics and Information Science Henan Polytechnic University Jiaozuo China

The t-distribution has a “fat tail” feature, which is more suitable than the normal probability density function to describe the distribution characteristics of return on assets. The difficulty of using t-distribution to price European options is that a fat tail can lead to a deviation in one integral required for option pricing. We use a distribution called logarithmic truncated t-distribution to price European options. A risk neutral valuation method was used to obtain a European option pricing model with logarithmic truncated t-distribution.

关键词： Option Pricing Logarithmic Truncated t-Distribution Asset Returns Risk-Neutral Valuation Approach