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Hypoxia signaling in human health and diseases:implications and prospects for therapeutics

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2787-2816页

作者： Zhen Luo Mingfu Tian ge yang Qiaoru Tan Yubing Chen geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu Guangdong Provincial Key Laboratory of Virology Institute of Medical MicrobiologyJinan UniversityGuangzhou 510632China Foshan Institute of Medical Microbiology Foshan 528315China The First Affiliated Hospital of Jinan University Guangzhou 510632China The Affiliated Shunde Hospital of Jinan University Foshan 528303China

Molecular oxygen(O2)is essential for most biological reactions in mammalian *** the intracellular oxygen content decreases,it is called *** process of hypoxia is linked to several biological processes,including pathogenic microbe infection,metabolic adaptation,cancer,acute and chronic diseases,and other stress *** mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during ***-inducible factors(HIFs)sense hypoxia to regulate the expressions of a series of downstream genes expression,which participate in multiple processes including cell metabolism,cell growth/death,cell proliferation,glycolysis,immune response,microbe infection,tumorigenesis,and ***,hypoxia signaling also interacts with other cellular pathways,such as phosphoinositide 3-kinase(PI3K)-mammalian target of rapamycin(mTOR)signaling,nuclear factor kappa-B(NF-κB)pathway,extracellular signal-regulated kinases(ERK)signaling,and endoplasmic reticulum(ER)*** paper systematically reviews the mechanisms of hypoxia signaling activation,the control of HIF signaling,and the function of HIF signaling in human health and *** addition,the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted,which would provide novel strategies for the design and development of therapeutic drugs.

关键词： diseases metabolism drugs

Existence results for generalized vector equilibrium problems with applications

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Applied Mathematics and Mechanics(English Edition) 2014年第7期35卷 913-924页

作者：杨明歌黄南京 Department of Mathematics Luoyang Normal University Department of Mathematics Sichuan University

By a coincidence theorem, some existence theorems of solutions are proved for four types of generalized vector equilibrium problems with moving cones. Applications to the generalized semi-infinite programs with the generalized vector equilibrium constraints under the mild conditions are also given. The results of this paper unify and improve the corresponding results in the previous literature.

关键词： generalized vector equilibrium problem generalized semi-infinite program,abstract convex space -map

Phosphorylation of NIR-II emitting Au nanoclusters for targeted bone imaging and improved rheumatoid arthritis therapy

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Aggregate 2024年第2期5卷 213-221页

作者： ge yang Kang Liu Yaru Wang Xinxin Pan Jingrun Ye Yue Li Fanglin Du Ting Feng Xun Yuan School of Materials Science and Engineering Qingdao University of Science and TechnologyQingdaoPR China School of Chemistry and Molecular Engineering Qingdao University of Science and TechnologyQingdaoPR China School of Polymer Science and Engineering Qingdao University of Science and TechnologyQingdaoPR China

Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and ***,an ultrasmall Au nanocluster(NC,<2 nm)-based theranostic probe is developed to achieve highly temporospat... 详细信息

Designing a theranostic probe for noninvasive bone imaging and bone disease therapy is both challenging and ***,an ultrasmall Au nanocluster(NC,geted photoluminescence(PL)imaging in the second near-infrared window(NIR-Ⅱ)and enhanced rheumatoid arthritis(RA)*** key design of the probe involves the surface phosphorylation of atomically precise NIR-Ⅱemitting Au_(44)*** phosphorylation enhances the bone-targeting ability of the probe due to the highly concentrated phosphate groups,allowing the probe to realize in vivo bone-targeted NIR-ⅡPL ***,benefiting from the enhanced bone-targeting ability,ultrasmall hydrodynamic diameter,and excellent anti-inflammation and immunomodulatory effects,the probe not only demonstrates superior therapeutic efficacy for RA rats,effectively restoring the destructed cartilage to nearly normal but also exhibits good renal clearance and benign *** favorable attributes cannot be achieved by commercial methotrexate used for RA *** study presents a new design paradigm for metal NC-based theranostic probes,offering the potential for high-resolution bone-targeted PL imaging and improved RA therapy.

关键词： Au nanocluster ligand engineering NIR-Ⅱluminescence-targeted bone imaging rheumatoid arthritis therapy

Effect improvement of drug pricing reform based on multi-channel coordination

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Journal of Southeast University(English Edition) 2020年第4期36卷 444-452页

作者： yang ge Zhao Lindu School of Economics and Management Southeast University Nanjing 211189 China

To improve the effect of the drug pricing reform,a business model of pharmaceutical e-commerce is introduced into the pharmaceutical supply ***,based on the measures of the drug pricing reform,a dual-channel model is established,consisting of a drugstore and a *** analysis of the model indicates that the reform leads to higher costs for ***,an e-pharmacy is added to the dual-channel supply ***,to reduce the home-delivery cost of the e-pharmacy,a multi-channel coordination strategy called“order online,delivery by drugstore”is *** comparing the optimal values under the two models with and without coordination strategy,respectively,the results show that the profits of the e-pharmacy and the drugstore increase while the retail prices of drugs drop,and a large number of patients are diverted from the ***,the business model of pharmaceutical e-commerce with multi-channel coordination can greatly improve the effect of the drug pricing reform.

关键词： drug pricing reform multi-channel coordination dual-channel model pharmaceutical e-commerce

Transarterial chemoembolization versus percutaneous microwave coagulation therapy for recurrent unresectable intrahepatic cholangiocarcinoma:Development of a prognostic nomogram

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 138-146页

作者： yang ge Seogsong Jeong Gui-Juan Luo Yi-Bin Ren Bao-Hua Zhang Yong-Jie Zhang Feng Shen Qing-Bao Cheng Cheng-Jun Sui Hong-yang Wang Qiang Xia Lei Chen School of Public Health Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 201805China Biliary Tract Department II Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Biliary Tract Department I Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Special Medical Care&Liver Transplantation Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Oncology Shanghai Cancer Center and Institutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver ***,there is no informa-tion regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma(ICC)after ***:A total of 275 patients with localized recurrent ICC who received either TACE(n=183)or PMCT(n=92)were studied.A propensity score matching analysis was performed to compare prognostic impact of TACE and *** factors for TACE and PMCT were identified *** nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve ***:Both TACE and PMCT provided curativeness in partial patients(5-year overall survival:21.4%and 6.1%,respectively),but TACE provided better survival benefit in both overall patients(hazard ratio[HR]=0.71;95%confidence interval[CI]:0.50–0.97;P=0.034)and propensity score matching analysis(HR=0.69;95%CI:0.47–0.98;P=0.041).Independent prognostic factors for TACE were tumor size>5 cm,poor differentiation,and major resection,whereas poor differentiation,hepatitis B virus infection,cholelithiasis,and lymph node metastasis were identified for *** predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70,***:TACE provided better survival benefits compared to ***,there was a disparity in prognostic factors,suggesting evaluation of the two nomograms may be supportive in modality *** prospective validation studies are required for the results to be applied in clinical medicine.

关键词： Bile duct cancer Biliary malignancy Cholangiocarcinoma Locoregional therapy Nomogram

考虑堆石料空间变异性的土石坝地震反应随机有限元分析

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岩土工程学报 2016年第10期38卷 1822-1832页

作者：杨鸽朱晟河海大学水文水资源与水利水电工程科学国家重点实验室江苏南京210098 国家能源局大坝安全监察中心浙江杭州311122 河海大学水工结构研究所江苏南京210098

探讨了一种将随机场模拟技术与有限元方法相结合的随机有限元法在土石坝地震反应分析中的应用途径。采用局部平均细分法模拟堆石料物理力学性质随机场,使得能够考虑堆石料的空间变异性。提出尽量利用建立材料物理性质与力学性质关系的... 详细信息

探讨了一种将随机场模拟技术与有限元方法相结合的随机有限元法在土石坝地震反应分析中的应用途径。采用局部平均细分法模拟堆石料物理力学性质随机场,使得能够考虑堆石料的空间变异性。提出尽量利用建立材料物理性质与力学性质关系的计算模型,以降低获取材料力学性质统计特性信息的成本。以一实际工程为例,采用该随机有限元法计算了堆石料的干密度、孔隙比、不均匀系数、平均粒径、Duncan–Chang E–B模型模量系数以及初始摩擦角具有不确定性时土石坝的随机地震响应及永久变形。结果表明:筑坝堆石料的不确定性会使大坝响应及永久变形发生一定程度的离散;忽略材料的不确定性可能导致低估大坝的地震反应;表征大坝地震反应的各性能指标并不一定都符合正态或对数正态分布。

关键词：土石坝地震反应堆石料空间变异性随机有限元法

Molecular Design and Property Prediction of High Density 4-Nitro-5-(5-nitro-1,2,4-triazol-3-yl)-2H-1,2,3-triazolate Derivatives as the Potential High Energy Explosives

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Chinese Journal of Structural Chemistry 2022年第2期41卷 123-131,I0011页

作者： yang Jing PANG Yu LI Min-Xian yang ge-Fei JIA Jing-Xian MENG Xiang-Jun LIU Li-Hua yang Xiao-Chun GAO Xiao-Zhen Department of Chemistry Tangshan Normal CollegeTangshan 063000China School of Chemical Engineering and Light Industry Guangdong University of TechnologyGuangzhou 510006China yangquan Municipal Key Laboratory of Quantum Manipulation Shanxi Institute of TechnologyYangquan 045000China

To search for potential energetic materials with large energy density and acceptable thermodynamics and kinetics stability,twelve derivatives of 4-nitro-5-(5-nitro-1,2,4-triazol-3-yl)-2H-1,2,3-triazolate(named A~L)are designed and analyzed by using density functional theory(DFT)calculations at the B3LYP/6-311G**level of *** molecular heats of formation(HOF),electronic structures,impact sensitivity(H_(50)),oxygen balance(OB)and density(ρ)are investigated by isodesmic reaction method and physicochemical ***,the detonation velocity(D)and detonation pressure(P)are calculated to study the detonation performance by Kamlet-Jacobs(K-J)*** results show that new molecule J(H_(50)=36.9 cm,ρ=1.90g/cm^(3),Q=1912.46 cal/g,P=37.82 GPa,D=9.22 km/s,OB=0.00),compound A(H_(50)=27.9 cm,ρ=1.93 g/cm^(3),Q=1612.93 cal/g,P=38.90 GPa,D=9.19 km/s)and compound H(H_(50)=37.3 cm,ρ=1.97 g/cm^(3),Q=1505.06cal/g,P=37.20 GPa,D=9.01 km/s)present promising effects that are far better RDX and HMX as the high energy density *** calculations can provide useful information for the molecular synthesis of novel high energy density materials.

关键词： 4-nitro-5-(5-nitro-1,2,4-triazol-3-yl)-2H-1,2,3-triazolate energetic materials density functional theory explosive

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin yang Jun yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu ge yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical Research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug Research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 *** aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,*** protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

Characteristics of LDPE and Oriented Montmorillonite Nanocomposites Produced by Electric Field-inducement

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高电压技术 2013年第8期39卷 1947-1951页

作者： BAI ge LIAO Ruijin yang Lijun YUAN Yuan GU Jia State Key Laboratory of Transmission & Distribution Equipments and Power System Safety and New Technology Chongqing University Chongqing 400030 China

In order to make montmorillonite (MMT) nanosheets disperse in low-density polyethylene (LDPE) with highly homogeneous orientation, alternating voltage is applied to molten LDPE with MMT nanosheets. The effect of electric field on the dispersion of MMT in the solidified LDPE is studied. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses suggest that the MMT nano- sheets are aligned with high anisotropy to the electric field direction, which is perpendicular to the LDPE film plane. Differential scanning calorimetry (DSC) results reveal that the crystallization degree of the oriented LDPE/MMT composite increases. Moreover, through a broadband dielectric spectroscopy analyzer, it is found that MMT manifests a significantly influence in the dielectric property of the oriented composite: the dielectric constant and loss tangent of the composite both become larger. Analysis shows that the electric field-induced torque caused by the polarization of MMT flakes is the main force inducing the orientation of the MMT flakes.

关键词：纳米复合材料 LDPE薄膜电场方向介电特性蒙脱土低密度聚乙烯扫描电子显微镜差示扫描量热法