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Journal of Pharmaceutical Analysis 2023年第4期13卷 340-354页

作者： Duanping Sun Ying Ma Maoqiang Wu Zuanguang Chen luyong zhang Jing Lu Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Center for Drug Research and DevelopmentGuangdong Pharmaceutical UniversityGuangzhou510006China Key Specialty of Clinical Pharmacy The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhou510699China National and Local United Engineering Lab of Druggability and New Drugs Evaluation School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time *** tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid *** are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary ***-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition *** this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic ***,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV ***,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

关键词： Aptamer Microfluidic Circulating tumor cells Extracellular vesicles Bioanalysis

Effective Capacity in Cognitive Radio Networks with Relay and Primary User Emulator

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China Communications 2019年第11期16卷 130-145页

作者： luyong zhang Yijie Yang Xuan Li Jinhua Chen Yunbing Chi Institute of Information and Communication Engineering Beijing University of Posts and Telecommunications

In this paper,the transmission performances are studied in cognitive radio networks with primary user emulator and relay *** the proposed network,the users include primary users,secondary users and primary user *** decreasing access priority of the users are primary users,primary user emulators and secondary *** user access to the network results in different transmission *** impose interference power constraints on the secondary users to protect the primary users from being *** also adopt the transmission mechanism that transits among more than one secondary transmitters,secondary receivers and *** transition models of the transmission states are proposed to describe the transmission *** investigate the transmission performances,the theory of effective capacity is *** transmission performances in terms of effective capacity are expressed and demonstrated under different transmission *** overall effective capacity,as the overall data traffic in the cognitive radio network,is ***,the overall effective capacity is demonstrated under different transmission *** results show the greedy transmission strategy outperforms the rest of the transmission 8 policies in the overall effective *** a larger number of the users,the effective capacity converges to a certain value.

关键词： cognitive radio primary user emulator(PUE) relay communication effective capacity transmission strategy

A new perspective of triptolide-associated hepatotoxicity:the relevance of NF-κB and NF-κB-mediated cellular FLICE-inhibitory protein

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Acta Pharmaceutica Sinica B 2020年第5期10卷 861-877页

作者： Ziqiao Yuan Zihang Yuan Muhammad Hasnat Haoran zhang Peishi Liang Lixin Sun Zhenzhou Jiang luyong zhang Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China Center for Drug Research and Development Guangdong Pharmaceutical UniversityGuangzhou 510006China Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Quality Control and Pharmacovigilance(China Pharmaceutical University) Ministry of EducationNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Institute of Pharmaceutical Sciences University of Veterinary and Animal SciencesLahore 54000Pakistan College of Traditional Chinese Medicine Guangdong Pharmaceutical UniversityGuangzhou 510006China

Previously,we proposed a new perspective of triptolide(TP)-associated hepatotoxicity:liver hypersensitivity upon lipopolysaccharide(LPS)***,the mechanisms for TP/LPSinduced hepatotoxicity remained *** present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS ***-αinhibitor,etanercept,was injected intraperitoneally into mice to investigate whether induction of TNF-αby LPS participated in the liver injury induced by TP/LPS *** and hepatocytes pretreated with TP were stimulated with recombinant TNF-αto assess the function of TNF-αin TP/LPS ***,time-dependent MF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in ***,overexpression of cellular FLICEinhibitory protein(FLIP),the most potent NF-κB-mediated pro-survival protein,was measured in vivo and in vitro to assess its function in TP/LPS-induced *** counteracted the toxic reactions induced by TP/***-treatment sensitized mice and hepatocytes to TNF-α,revealing the role of TNF-αin TP/LPS-induced *** studies revealed that TP inhibited NF-κB dependent pro-survival signals,especially FLIP,induced by LPS/TNF-α.Moreover,overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in *** and hepatocytes treated with TP were sensitive to TNF-α,which was released from LPS-stimulated immune *** and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

关键词： Triptolide LPS TNF-x NF-KB FLIP

Optimization of hypocrellin B derivative amphiphilicity and biological activity

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Chinese Science Bulletin 2009年第12期54卷 2045-2050页

作者： LIU Xin XIE Jie zhang luyong CHEN HongXia GUYing ZHAO JingQuan Beijing National Laboratory for Molecular Sciences (BNLMS) and Key Laboratory of Photochemistry Institute of Chemistry Chi- nese Academy of Sciences Beijing 100080 China Department of Laser Medicine Chinese People's Libration Army General Hospital Beijing 100853 China

To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-1-propanesulfonic acid and 4-amino-1-butanesulfonic acid substituted hypocrellin B, named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline (PBS) is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS, 5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B (THB), but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.

关键词：竹红菌乙素生物活性衍生物优化超氧阴离子自由基 A549细胞磷酸盐缓冲液电子顺磁共振

Total glucosides of Rhizoma Smilacis Glabrae:a therapeutic approach for psoriasis by regulating Th17/Treg balance

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Chinese Journal of Natural Medicines 2023年第8期21卷 589-598页

作者： TANG Yingzhan YU Jingyi ZHAO Wen LIU Juyan PENG Hongying zhang Haoran JIANG Zhenzhou YU Qinwei zhang luyong New drug screening center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing 210009China Guangzhou Baiyunshan Jingxiutang Pharmaceutical Co. Ltd.Guangzhou 510130China Guangzhou Pharmaceutical Holdings Co. Ltd.Guangzhou 510103China Center for Drug Research and Development Guangdong Pharmaceutical UniversityGuangzhou 510006China

Total glucosides of Rhizoma Smilacis Glabrae(RSG)are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T *** this study,we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material *** findings revealed significant improvements upon administration of RSG in an imiquimod(IMQ)-induced psoriasis *** improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema,ulceration,and *** transcriptome sequencing and T-cell flow sorting assay,we identified notable effects of RSG on the modulation of various cellular ***,RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase ***,RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial *** particular interest,we discovered thatβ-sitosterol,sitostenone,stigmasterol,smiglanin,and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT *** summary,our study highlights the therapeutic potential of RSG in the treatment of psoriasis,attributed to its ability to regulate the Th17/Treg *** findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.

关键词： Psoriasis Rhizoma Smilacis Glabrae Th17/Treg balance Inflammation Epithelium development

A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis

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Acta Pharmaceutica Sinica B 2021年第3期11卷 708-726页

作者： Tailin He Jialin Shang Chenglong Gao Xin Guan Yingyi Chen Liwen Zhu luyong zhang Cunjin zhang Jian zhang Tao Pang State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug ScreeningJiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesChina Pharmaceutical UniversityNanjing 210009China Medicinal Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Neurology of Drum Tower Hospital Medical School and the State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjing 210008China

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke,but how to control the overactive neuroinflammation is still a long-standing ***,we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia,which were abolished by silencing ***-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811stimulation and is required for the anti-inflammatory effects of *** found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate ***,our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS,but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional ***,MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients,underlying an interesting translational *** together,MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.

关键词： SIRT6 activator Neuroinflammation Ischemic stroke Deacetylation Microglia Macrophage FOXC1 EZH2

Patterning of large area nanoscale domains in as-grown epitaxial ferroelectric PbTiO_(3)films

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Journal of Materiomics 2023年第1期9卷 56-61页

作者： luyong zhang Guo Tian Wenda Yang Dongfeng Zheng Chuanjie Lin Jianbiao Xian Yihang Guo Xingchen zhang Xiuqin Qiu Lanping zhang Zhen Fan Deyang Chen Zhipeng Hou Minghui Qin Jun-Ming Liu Xingsen Gao Guangdong Provincial Key Laboratory of Optical Information Materials South China Academy of Advanced OptoelectronicsSouth China Normal UniversityGuangzhou510006China Laboratory of Solid State Microstructures and Innovation Center of Advanced Microstructures Nanjing UniversityNanjing210093China

Effective tuning of nanoscale domain structures provides fundamental basis for controlling and engineering of various functionalities in ferroelectric *** this work,we demonstrate the precise patterning of nanoscopic domain structures in as-grown epitaxial PbTiO_(3)(PTO)films by merely introducing an ultrathin pre-patterned doping layer(e.g.,Fe-doped PTO).The doping layer can effectively reverse the interfacial built-in bias,consequent to a reversed initial polarization reorientation in the as-grown film,which makes it possible to transfer the nano-patterns in the doping layer into the domain structure of ferroelectric *** instance,we have successfully fabricated large area ordered array of nanoscale cylindrical domains(downward polarization)embedded in the matrix domain with opposite polarization(upward polarization)in PTO *** nanoscale cylinder domains also allow deterministic and reversible erasure and creation induced by biased tip *** results provide an effective pathway for on-demand patterning of large area nanoscale domains in the as-grown films,which may find applications in a wide range of nanoelectronic devices.

关键词： Ferroelectric thin film Patterning of nanoscale domain Domain engineering Nanoscale cylindrical domains

Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor

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Neural Regeneration Research 2012年第34期7卷 2705-2712页

作者： Weigang Duan Ling Que Xiaoman Lv Qifeng Li Hua Yin luyong zhang Key Laboratory of Molecular Biology for Sinomedicine Yunnan University of Traditional Chinese Medicine New Drug Screening Center China Pharmaceutical University

In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors （Y27632 and Fasudil）, a cyclooxygenase-1 selective inhibitor （SC560）, and a cyclooxygenase-2 inhibitor （NS398）. We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance.

关键词： Rho-associated kinase inhibitors Y27632 fasudil neurite cyclooxygenase 2 inhibitors drugtolerance

Controlled manipulation of conductive ferroelectric domain walls and nanoscale domains in BiFeO_(3) thin films

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Journal of Materiomics 2022年第2期8卷 274-280页

作者： Dongfeng Zheng Guo Tian Yadong Wang Wenda Yang luyong zhang Zoufei Chen Zhen Fan Deyang Chen Zhipeng Hou Xingsen Gao Qiliang Li Jun-Ming Liu Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials and Institute for Advanced Materials South China Academy of Advanced OptoelectronicsSouth China Normal UniversityGuangzhou510006China Songshan Lake Materials Laboratory Dongguan Guangdong523808China Department of Electrical and Computer Engineering George Mason UniversityFairfaxVirginia22030USA Laboratory of Solid State Microstructures and Innovation Center of Advanced Microstructures Nanjing UniversityNanjing210093China

Recently,there is a surge of research interest in configurable ferroelectric conductive domain walls which have been considered as possible fundamental building blocks for future electronic *** this work,by using piezoresponse force microscopy and conductive atomic force microscopy,we demonstrated the controlled manipulation of various conductive domain walls in epitaxial BiFeO_(3) thin films,*** domain walls(NDW)and charged domain walls(CDWs).More interestingly,a specific type of nanoscale domains was also identified,which are surrounded by highly conductive circular *** nano-scale domains can also be controlled created and erasured by applying local field via conductive probe,which allow nondestructive current readout of different domain states with a large on/off resistance ratio up to *** results indicate the potential to design and develop high-density non-volatile ferroelectric memories by utilizing these programable conductive nanoscale domain walls.

关键词： BiFeO_(3)thin film Conductive domain wall Nanoscale domain High density memory

补骨脂素对四氯化碳致小鼠急性肝损伤的改善作用

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中国药科大学学报 2021年第5期52卷 596-602页

作者：张艳江振洲张陆勇中国药科大学药物科学研究院新药筛选中心南京210009 广东药科大学新药研发中心广州510006

研究补骨脂素(psoralen,PSO)对四氯化碳(CCl_(4))致小鼠急性肝损伤的改善作用及其机制。雌性C57BL/6J小鼠连续灌胃补骨脂素或阳性对照药烯丙基化硫(DAS)4 d,第4天腹腔注射CCl_(4),建立CCl_(4)致急性肝损伤小鼠模型。检测血清生化指标丙... 详细信息

研究补骨脂素(psoralen,PSO)对四氯化碳(CCl_(4))致小鼠急性肝损伤的改善作用及其机制。雌性C57BL/6J小鼠连续灌胃补骨脂素或阳性对照药烯丙基化硫(DAS)4 d,第4天腹腔注射CCl_(4),建立CCl_(4)致急性肝损伤小鼠模型。检测血清生化指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平;HE染色观察肝脏病理学变化;Western blot检测细胞色素P4502E1(CYP2E1)的蛋白水平;免疫组织化学染色(IHC)检测CYP2E1的蛋白水平;RT-PCR检测CYP2E1以及炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的基因水平。与模型组相比,补骨脂素能够改善CCl_(4)引起的炎性细胞浸润以及肝细胞坏死情况,显著降低血清ALT、AST水平,下调炎症因子TNF-α和IL-6的水平,抑制CYP2E1的蛋白表达。结果表明,补骨脂素对CCl_(4)致小鼠急性肝损伤具有改善作用,其机制可能是通过抑制CYP2E1的蛋白表达发挥药效作用。

关键词：补骨脂素四氯化碳急性肝损伤细胞色素P4502E1