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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

Signal Transduction and Targeted Therapy 2024年第7期9卷 3063-3076页

作者： Wenjing Zai Min Yang Kuan Jiang Juan Guan huijing wang Kongying Hu Chao Huang Jieliang Chen Wei Fu Changyou Zhan Zhenghong Yuan Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Research Unit of Cure of Chronic Hepatitis B Virus Infection(CAMS)Shanghai Frontiers Science Center of Pathogenic Microbes and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghaiP.R.China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghaiP.R.China Eye Institute and Department of Ophthamology Eye and ENT HospitalFudan UniversityShanghaiP.R.China Pharmacy Department of Huashan Hospital Fudan UniversityShanghaiP.R.China Institute of Pediatric Translational Medicine Shanghai Institute for Pediatric Congenital Heart DiseaseShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Institute of Infectious Disease and Biosecurity ShanghaiP.R.China

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral *** synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and *** lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DMG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP *** efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for *** results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety *** studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 *** adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.

关键词： formulation enable offering

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Long-Range Electronic Effect-Promoted Ring-Opening Polymerization of Thioctic Acid to Produce Biomimetic Ionic Elastomers for Bioelectronics

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CCS Chemistry 2024年第3期6卷 761-773页

作者： Hongfei Huang huijing wang Lijie Sun Ruohan Zhang Luzhi Zhang ZekaiWu Yaxuan Zheng Yang wang Wei Fu Youwei Zhang Rasoul Esmaeely Neisiany Zhengwei You State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringInstitute of Functional MaterialsDonghua UniversityResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications(China Textile Engineering Society)Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineShanghai 201620 Institute of Pediatric Translational Medicine Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127 Department of Materials and Polymer Engineering Faculty of EngineeringHakim Sabzevari UniversitySabzevar ***

Poly(disulfide)s have been widely used in flexible wearable electronics,smart materials,and drug *** synthesis of poly(disulfide)s usually utilizes external stimuli or toxic initiators to promote the ***,we indicated that the long-range electronic effect can significantly alter the reactivity of the disulfide ***,we established deprotonation-promoted ring-opening polymerization of thioctic acid(TA)as a highly effective and simple method to synthesize poly(disulfide)s due to the long-range electronic effect and nucleophilic *** external stimuli and initiators,simple mixing of TA and deprotonation reagent,choline bicarbonate,in different ratios at room temperature rapidly produced a series of high molecular weight(up to 772 kDa)ionic liquid crystal poly(disulfide)s elastomers with room temperature self-healing ability,adjustable conductivity(2.39×10^(−2)∼0.28×10^(−2)S m^(−1)),degradability,biocompatibility,antibacterial property,and tissue-like softness(Young’s moduli ranging from 18.2±6.0 to 111.1±36.7 kPa).The experiments and density functional theory calculations also revealed the principle of long-range electronic effect to establish a new synthetic strategy of poly(disulfide)s with superior properties favorable for bioelectronics.

关键词： self-healing elastomers thioctic acid ionic liquid bioelectronics

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内蒙古地区高校英语教师科研环境研究

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河北开放大学学报 2024年第3期29卷 98-101页

作者：王慧晶内蒙古工业大学外国语学院内蒙古呼和浩特010080

本研究通过收集并分析多种数据,包括来自该地区120名英语教师的问卷调查、6次访谈和30份叙述性询问和实地观察,展现出内蒙古地区高校英语教师科研环境的总体情况。数据表明英语教师的研究认知与研究实践、产出与投入、教师对科研支持的... 详细信息

本研究通过收集并分析多种数据,包括来自该地区120名英语教师的问卷调查、6次访谈和30份叙述性询问和实地观察,展现出内蒙古地区高校英语教师科研环境的总体情况。数据表明英语教师的研究认知与研究实践、产出与投入、教师对科研支持的期望与实际得到的帮助存在差异。英语教师的科研环境是一个复杂的结构,由该地区的个人、人际和制度因素相互作用塑造,尤其是个体与环境之间的相互作用。希望由此产生对教师科研环境及专业发展的深入思考和积极影响。

关键词：科研环境英语教师研究内蒙古

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Adhesion hysteresis of a film-terminated fibrillar array

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Science China(Physics,Mechanics & Astronomy) 2012年第6期55卷 1026-1031页

作者： YAN ShunPing HE LingHui wang huijing Chinese Academy of Sciences Key Laboratory of Mechanical Behavior and Design of Materials University of Science and Technology of ChinaHefei 230026China Department of Computer Application Shenzhen Institute of lnforrnation TechnologyShenzhen 518172China

Motivated by the recent biomimic design of microstructured adhesive surfaces,we study adhesion between a film-terminated fibrillar array and a rigid *** a two-dimensional model and ignoring the deformation of the fibers and the backing layer,we show that the adhesion behavior is dominated by a dimensionless parameter reflecting the global flexibility of the terminal *** particular,if the parameter is larger than 0.4,the adhesion is reversible;otherwise one or more hysteresis loops will appear after an approach-retraction cycle,leading to significant increase in the specific separation *** result is expected to help not only optimal design of the structure,but also other applications such as micro-manipulation in micromechanical systems.

关键词： adhesion hysteresis film-terminated fibrillar array intermolecular force

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基于布鲁姆教学目标分类整合课程教学模式的探索与实践

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中国继续医学教育 2024年第4期16卷 11-15页

作者：周波杨智昉汪慧菁上海健康医学院基础医学院上海201318

以器官系统为中心课程整合的医学教育改革视域下,传统教学模式远不能满足课程教学需求。根据基础医学整合课程特点,以“抗消化系溃疡药物”为实例,探索基于布鲁姆教学目标分类理论的线上线下混合式教学模式。课前,以线上学习平台实现识... 详细信息

以器官系统为中心课程整合的医学教育改革视域下,传统教学模式远不能满足课程教学需求。根据基础医学整合课程特点,以“抗消化系溃疡药物”为实例,探索基于布鲁姆教学目标分类理论的线上线下混合式教学模式。课前,以线上学习平台实现识记低阶教学目标;课中,以线下辅以线上教学,通过多元化学习任务实现理解、应用、分析等高阶教学目标;课后,利用各种信息化学习资源提升课堂所学内容,实现评价、创造等最高级教学目标。通过对基于布鲁姆教学目标分类理论的混合式教学模式的实践、总结和反思,以期为临床医学专业器官系统为中心整合课程的教学方法提供思路和具体的借鉴实例。

关键词：混合式教学布鲁姆教学目标分类理论整合课程以器官系统为中心临床医学基础医学教学

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Asymmetric synthesis of ABC tricyclic systems in Daphniphyllum alkaloid

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Chinese Chemical Letters 2020年第3期31卷 685-688页

作者： huijing wang Qiuyan Dong Qinxia Xie Pei Tang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Chongqing Key Laboratory of Natural Product Synthesis and Drug Research School of Pharmaceutical SciencesChongqing UniversityChongqing 401331China Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa Jolla 92093-0934United States

Efficient synthetic routs for the direct and rapid construction of[5-6-6]ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully *** the daphmanidin A-type,the synthesis of[5-6-6]tricyclic framework utilize a HCl-mediated intramolecular Aldol reaction to construct the bicyclo[2.2.2]octane core and a thermal condensation to afford the ABC ring *** addition,for the calyciphylline A-type,an improved synthesis of ABC[5-6-6]tricyclic system was developed,featuring an introduction of methyl ester group at C2 before the Pd-catalyzed intramolecular oxidative alkylation to construct the desired bowl-shape tricyclic core with stereochemical control.

关键词： Daphniphyllum alkaloid Calyciohylline N 21-Deoxymacropodumine D ABC tricyclic framework Intramolecular Aldol reaction Pd-catalyzed intramolecular oxidative alkylation

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蒲公英提取物对脑出血大鼠的治疗作用及机制研究

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中华老年心脑血管病杂志 2024年第2期26卷 212-216页

作者：张秀峰李小菲王静辉王慧静王立雯甄诚王鹏飞刘熙鹏河北北方学院附属第一医院神经外科张家口075000

目的研究蒲公英提取物对自发性脑出血(ICH)大鼠的治疗作用及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。方法通过脑定位注射Ⅳ型胶原酶诱导建立48只ICH大鼠模型,随机分为模型组、蒲公英提取物组、Nrf2抑制剂(ML385)... 详细信息

目的研究蒲公英提取物对自发性脑出血(ICH)大鼠的治疗作用及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。方法通过脑定位注射Ⅳ型胶原酶诱导建立48只ICH大鼠模型,随机分为模型组、蒲公英提取物组、Nrf2抑制剂(ML385)组和蒲公英提取物+ML385组,每组12只,另选12只大鼠作为假手术组。以药物分组处理后,进行大鼠神经功能损伤评分;检测大鼠血脑屏障功能、海马神经元细胞凋亡率、血清环氧化酶2(COX-2)、白细胞介素6(IL-6)、诱导型一氧化氮合酶(iNOS)及脑组织过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、活性氧、丙二醛水平和Nrf2/HO-1信号通路蛋白表达。结果与假手术组比较,模型组大鼠神经功能缺损评分、伊文思蓝渗出量、海马神经元细胞凋亡率、血清COX-2、IL-6、iNOS水平、脑组织活性氧、丙二醛水平显著升高(P<0.05),CAT、GSH-Px、Nrf2、HO-1蛋白表达水平显著降低(P<0.05)。与蒲公英提取物组比较,蒲公英提取物+ML385组大鼠神经功能评分[(2.54±0.23)分vs(1.43±0.19)分]、伊文思蓝渗出量[(22.15±3.61)ng/mg vs(6.54±1.24)ng/mg]、海马神经元细胞凋亡率[(31.97±5.26)%vs(3.51±0.94)%]、血清COX-2[(5.82±1.16)ng/ml vs(1.34±0.42)ng/ml]、IL-6[(1.47±0.31)ng/ml vs(0.43±0.14)ng/ml]、iNOS[(59.91±10.36)U/ml vs(13.94±3.78)U/ml]、脑组织活性氧[(4.70±0.45)U/kg vs(1.70±0.51)U/kg]、丙二醛水平[(3.72±0.52)nmol/mg vs(1.17±0.34)nmol/mg]显著升高(P<0.05),CAT[(2.54±0.59)U/mg vs(5.68±1.04)U/mg]、GSH-Px[(8.01±0.86)U/mg vs(16.97±3.03)U/mg]、Nrf2(0.67±0.13 vs 1.07±0.19)、HO-1(0.55±0.07 vs 0.86±0.10)蛋白表达水平显著降低(P<0.05)。结论蒲公英提取物可通过激活Nrf2/HO-1信号通路增强ICH大鼠抗氧化活性,阻止炎症和氧化应激反应进展,抑制海马神经元细胞凋亡,修复血脑屏障功能,改善大鼠神经功能。

关键词：脑出血大鼠,Sprague-Dawley 蒲公英属蒲公英提取物

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Bifunctional copper modified graphitic carbon nitride catalysts for efficient tetracycline removal:Synergy of adsorption and photocatalytic degradation

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Chinese Chemical Letters 2020年第10期31卷 2789-2794页

作者： huijing wang Jun Zhang Pu wang Linlin Yin Yu Tian Junjing Li State Key Laboratory of Urban Water Resources and Environment(SKLUWRE) School of EnvironmentHarbin Institute of TechnologyHarbin 150090China State Key Laboratory of Separation Membranes and Membrane Processes School of Environmental and Chemical EngineeringTianjin Polytechnic UniversityTianjin 300387China

In order to efficiently re move tetracycline in wastewater through the synergistic effect of adsorption and photocatalytic degradatio n,a series of novel composite materials(Cu doped g-C_(3)N_(4))were synthesized by two-pot hydrothermal *** was found that the composite materials with optimized ratio(Cu/CN-1)displayed outstanding adsorption and photocatalytic performance as compared with pure g-C_(3)N_(4) *** removal efficiency of tetracycline(TC,50 mg/L)reached almost 99%within 30 min by Cu/CN-1 through the synergy of adsorption and photocatalysis under visible-light irradiation,which was the highest re moval efficiency ever *** adsorption kinetics and isotherms of TC on the Cu/CN-1 were well fitted with the pseudo-second-order kinetic model and Langmuir model,***,it was confirmed that the main effective reactive groups were O_(2)^·and h^(+) in photocatalytic *** Cu/CN-1 exhibited high stability and excellent reusability after five cycle ***,the mechanism of synergy between Cu and g-C_(3)N_(4) was proposed:on the one hand,the decoration of Cu particles significantly increased the adsorption sites of Cu/CN-1 to tetracycline,on the other hand,the modification of Cu particles effectively inhibits charge recombination and broadens the visible light absorption range of the *** study provided a promising photocatalyst to be used for TC removal in the actual wastewater.

关键词： Carbon nitride Tetracycline Adsorption Photocatalysis Environment remediation

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基于TLR-2/MyD88/NF-κB通路探讨养阴清肺汤加味对肺炎支原体感染小鼠炎症的影响

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中华中医药学刊 2024年第2期42卷 79-83,I0018页

作者：齐兆东吴振起王慧婧张心放梁翔宇辽宁中医药大学附属第二医院辽宁沈阳110034 辽宁中医药大学辽宁沈阳110847

目的探讨养阴清肺汤加味(Yangyin Qingfei decoction plus,YQDP)对肺炎支原体(Mycoplasma pneumoniae,MP)感染小鼠炎症反应及Toll样受体2(Toll-like receptor 2,TLR-2)/髓样分化因子88(Myeloid differentiation factor 88,MyD88)/核转录因子-κB(Nuclear factor-κB,NF-κB)信号通路的影响。方法选取BALB/c小鼠60只,随机分为正常组、模型组、阿奇霉素组、YQDP低、中、高剂量组,每组10只,除正常组外均建立MP感染小鼠模型,模型建立成功后开始给药治疗并于第7天取材。采用HE染色法观察小鼠的肺部病理改变情况,ELISA法检测血清中白介素-6(Interleukin-6,IL-6)、IL-8(Interleukin-8)、IL-17(Interleukin-17)水平,RT-PCR法、Western blot法检测TLR-2、MyD88、NF-κB mRNA及蛋白表达水平。结果与正常组比较,模型组小鼠大部分肺泡结构破坏严重,完整肺泡较少,肺泡间隔明显增厚并可见大量炎性细胞,血清中IL-6、IL-8、IL-17含量明显升高(P<0.05),肺组织中TLR-2、MyD88、NF-κB mRNA及蛋白表达量升高(P<0.05)。与模型组比较,给予阿奇霉素、YQDP治疗后,小鼠肺组织病理显示肺泡结构有明显恢复,肺泡周围存在的炎性细胞浸润均有不同程度减少,血清中IL-6、IL-8、IL-17含量明显降低(P<0.05),肺组织中TLR-2、MyD88、NF-κB mRNA及蛋白表达量降低(P<0.05),并且YQDP治疗组的降低趋势与其低、中、高剂量呈现依赖性。结论YQDP可能通过调控TLR-2/MyD88/NF-κB信号通路,起到减轻MP感染小鼠肺部炎症作用。

关键词：养阴清肺汤加味肺炎支原体炎症信号通路小鼠

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Classification of and the latest photoelectric therapy for epidermal nevi

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Chinese Journal of Plastic and Reconstructive Surgery 2022年第2期4卷 91-96页

作者： Liyun Liu huijing wang Jiying Dong Anhui Medical College Anhui No.2 Provincial People’s HospitalHefei 230601AnhuiChina Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Laser and Aesthetic Medicine Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

An epidermal nevus(EN)is a common disease of various types,including verrucous EN,nevus sebaceous,inflammatory linear verrucous EN,Becker nevus,smooth muscle hamartoma,and nevus *** syndrome is a serious and difficult-to-treat syndrome that is complicated by two or more abnormal organs or *** date,the mechanism of an EN is still unclear,and the therapies remain *** most frequently used treatments are surgery and laser *** drugs have also been *** EN requires more attention,and further research is needed to provide appropriate and effective treatments for each patient.

关键词： Epidermal nevus Epidermal nevus syndrome Verrucous epidermal nevus Nevus sebaceous Inflammatory linear verrucous epidermal nevus Becker nevus Smooth muscle hamartoma Nevus comedonicus

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