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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA jing-wei yao Yin LI Xian-ming DENG Bing XU Department of Hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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热补针法对类风湿关节炎寒证家兔膝关节滑膜组织缺氧诱导因子1α和糖酵解活性的影响

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针刺研究 2024年第6期49卷 585-593页

作者：李向军李福欣井维尧刘翠刘莉梅张星华张枫帆陈平杜小正甘肃省中医院风湿骨病科兰州730050 甘肃中医药大学针灸推拿学院兰州730000 甘肃省中医院针灸科兰州730050

目的:观察热补针法对类风湿关节炎(RA)寒证家兔膝关节滑膜炎性反应及滑膜组织、血清中缺氧诱导因子1α(HIF-1α)、糖酵解活性的影响,探讨热补针法治疗RA的机制。方法:选取32只新西兰兔随机分为正常组、模型组、抑制剂组、热补针法组,每... 详细信息

目的:观察热补针法对类风湿关节炎(RA)寒证家兔膝关节滑膜炎性反应及滑膜组织、血清中缺氧诱导因子1α(HIF-1α)、糖酵解活性的影响,探讨热补针法治疗RA的机制。方法:选取32只新西兰兔随机分为正常组、模型组、抑制剂组、热补针法组,每组8只。采用卵蛋白联合弗氏完全佐剂诱导及低温冷冻法复制RA寒证模型。抑制剂组给予2-甲氧基雌二醇腹腔注射,热补针法组给予热补针法针刺“足三里”,留针30 min。各组干预均1次/d,连续14 d。观察家兔膝关节周径及痛阈变化;采用ELISA法检测家兔血清中还原型辅酶Ⅱ(NADPH)、己糖激酶(HK2)、6-磷酸果糖激酶2/2,6-二磷酸果糖激酶3(PFKFB3)含量;HE染色法观察家兔膝关节滑膜组织形态变化;免疫组织化学法检测家兔膝关节滑膜组织中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-17的阳性表达;分光光度法检测家兔膝关节滑膜组织中乳酸含量;Western blot法检测膝关节滑膜组织中HIF-1α、乳酸脱氢酶(LDHA)、丙酮酸激酶2(PKM2)蛋白表达水平。结果:干预后,与正常组比较,模型组家兔膝关节周径增大(P<0.05),痛阈值降低(P<0.05),可见滑膜细胞中度增生及炎性浸润,滑膜组织病理评分升高(P<0.05),滑膜组织中TNF-α、IL-1β、IL-6、IL-17阳性表达及乳酸含量均升高(P<0.05),血清NADPH、HK2、PFKFB3含量及滑膜组织中HIF-1α、LDHA、PKM2蛋白表达水平均升高(P<0.05)。与模型组比较,抑制剂组及热补针法组家兔膝关节周径缩小(P<0.05),痛阈值升高(P<0.05),滑膜增生、炎性细胞浸润均改善,滑膜组织病理评分降低(P<0.05),滑膜组织中TNF-α、IL-1β、IL-6、IL-17阳性表达及乳酸含量均下降(P<0.05),血清NADPH、HK2、PFKFB3含量及滑膜组织中HIF-1α、LDHA、PKM2蛋白表达水平均下降(P<0.05)。与抑制剂组比较,热补针法组家兔滑膜组织病理评分升高(P<0.05),滑膜组织中TNF-α、IL-1β、IL-6、IL-17阳性表达及乳酸含量均升高(P<0.05),血清NADPH、HK2、PFKFB3含量及滑膜组织中HIF-1α、LDHA、PKM2蛋白表达水平均升高(P<0.05)。结论:热补针法干预RA寒证家兔可提高痛阈,减小膝关节周径,抑制炎性反应,其作用机制与下调HIF-1α及糖酵解活性相关。

关键词：类风湿关节炎热补针法糖酵解缺氧诱导因子1α 炎性反应

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Cavitation Erosion Behavior of CrMnN Duplex Stainless Steel in Distilled Water and 3% NaCl Solution

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Journal of Materials Science & Technology 2003年第4期19卷 346-350页

作者： Suzhen LUO, Yugui ZHENG, wei LIU, Heming jing, Zhiming yao and wei KEState Key Laboratory for Corrosion and Protection, Institute of Metai Research, Chinese Academy of Sciences, Shenyang 110016, China Lab. for Corrosion and Protection Inst. of Metal Res. Chinese Acad. of Sci. Shenyang 110016 China

The cavitation erosion (CE) behavior of CrMnIM ferrite-austenite duplex stainless steel in distilled water and 3% NaCI solution was investigated by using a magnetostrictive-induced CE facility. The damaged surfaces were observed by scanning electron microscope (SEM). It was found that the CE resistance of CrMnN steel was higher than that of OCrl3Ni5Mo steel. The mass loss rate of CrMnN steel in distilled water was similar to that in 3% NaCI except at the early stage of CE. The failure mode of ferrite phase was brittle fracture, which had adverse effect on the resistance to CE, while the failure of austenite phase was a ductile failure in CrMnN steel. The excellent resistance to CE was related to the good mechanical properties of austenitic phase and the consumption of CE energy by plastic deformation involving slip and twinning.

关键词： Cavitation erosion CrMnN duplex stainless steel Microstructure Ferrite Austenite Plastic deformation

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Biogenesis of Rab14-positive Endosome Buds at Golgi-endosome Contacts by the RhoBTB3-SHIP164-Vps26B Complex

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当代医学科学（英文） 2024年第4期44卷 864-866页

作者： jing-ru WANG Jun-yao ZHANG wei-Ke JI Department of Biochemistry and Molecular Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Biochemistry and Molecular Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Cell Architecture Research Center Huazhong University of Science and TechnologyWuhan 430030China State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and TechnologyWuhan 430030China Shenzhen Bay Laboratory Shenzhen 518132China

As one of the basic processes of cellular activity,endocytosis sorting determines the fate of many proteins on the endosomal membranes,thus affecting a variety of important cellular processes,such as nutrient uptake,cell signal transduction,intracellular ion homeostasis,*** dysregulation is closely related to various neurological diseases,metabolic disease,and immune disorders[1].Early endosomes(EEs)are crucial in cargo sorting within vesicular trafficking,cargos destined for the plasma membrane or the Golgi are first sorted into the specific membrane structure of the EE-EE buds,and then separated from the EE by membrane fission,and further returned to the plasma membrane or Golgi through a recycling *** that are destined for degradation remain in EE,and as the endosome matures,they are ultimately degraded in the ***,the EE buds play a key role in cargo sorting[2].Currently,the molecular mechanism of EE bud biogenesis is still not fully understood,and the molecular mechanism of membrane lipid regulation during budding is still unknown.

关键词： PHASE-SEPARATION PROTEIN VPS13

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Evaluation of the injection and plugging ability of a novel epoxy resin in cement cracks

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Petroleum Science 2024年第2期21卷 1211-1220页

作者： Guang-yao Leng wei Yan Hai-Mu Ye Er-Dong yao Ji-Bin Duan Zheng-Xian Xu Ke-Pei Li jing-Ru Zhang Zhong Li State Key Laboratory of Petroleum Resource&Prospecting China University of Petroleum(Beijing)Beijing102249China CNPC Liaohe Oilfield Gas Storage Co.LTD Panjin124000LiaoningChina CNOOC Research Institute Co. Ltd.Beijing100028China

Sustained casing pressure(SCP)is a crucial issue in the oil and gas production *** resins,exhibiting exceptional compressive strength,ductility,and shear bonding strength,have the potential to form reliable *** injectivity and sealing capacity of the epoxy resin is crucial parameters for the success of shallow remediation *** study aimed to develop and assess a novel solid-free resin sealant as an alternative to Portland cement for mitigating fluid *** investigation evaluated the viscosity,compressive strength,and brittleness index of the epoxy resin sealant,as well as its tangential and normal shear strengths in conjunction with casing *** flow characteristics and sealing abilities of conventional cement and epoxy resin were comparatively analyzed in *** results showed that the application of a viscosity reducer facilitated control over the curing time of the epoxy resin,ranging from 1.5 to 6 h,and reduced the initial viscosity from 865.53 to 118.71 m Pa,*** mechanical properties of the epoxy resin initially increased with a rise in curing agent content before experiencing a minor *** epoxy resin containing 30%curing agent exhibited optimal mechanical *** a 14-day curing period,the epoxy resin's compressive strength reached81.37 MPa,2.12 times higher than that of cement,whereas the elastic modulus of cement was 2.99 times greater than that of the epoxy *** brittleness index of epoxy resin is only 3.42,demonstrating high flexibility and *** tangential and normal shear strengths of the epoxy resin exceeded those of cement by 3.17 and 2.82 times,*** a 0.5 mm-wide crack,the injection pressure of the epoxy resin remained below 0.075 MPa,indicating superior injection and flow ***,the injection pressure of cement surged dramatically to 2.61 MPa within 5 *** breakthrough pressure of0.5 PV epoxy resin reached 7.53 MPa,decreasing the crack's perme

关键词： Sustained casing pressure Epoxy resin sealant Curing agent Viscosity reducer Mechanical properties Crack sealing

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Limits of Uneven Battery Power in Modular Multilevel Converter-based Battery Energy Storage Systems

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 686-695页

作者： yao Pan Xiaofeng Sun wei Zhao Xin Li yao Cai Institute of Electrical Engineering Yanshan UniversityQinhuangdao 066004China

For modular multilevel converter-based battery energy storage systems (MMC-BESS), uneven power among batteries of SMs will be deduced by battery aging, battery fault, etc., which will degrade performance and even lead to system failure. For maintaining the balance of capacitor voltage, this paper analyzes the limits of the uneven power of batteries, which are presented as the current limits in this paper. According to analysis, an analytical method is proposed that only the dc and fundamental frequency components of the arm current are used to calculate current limits. With the current limits it is able to evaluate the reasonability of power distribution among batteries. Meanwhile, increase of fundamental frequency component will enhance the current limits, and the dc component determines the size relationship between the absolute values of the upper and lower current limits. Finally, simulation model and experiment prototype are built for verifying the theoretical analysis and current limits calculation method, and satisfactory results are provided.

关键词： Arm current balance of capacitor voltage current limits MMC-BESS uneven power

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Core-shell nanoparticle enhanced Raman spectroscopy in situ probing the composition and evolution of interfacial species on PtCo surfaces

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Nano Research 2024年第6期17卷 4687-4692页

作者： jing Liu Han-Liang Zhong Xiangyu Li Mu-Fei Yue wei-Min Yang Xueqiu You jing-Hua Tian yao-Hui Wang Jian-Feng Li Fujian Provincial Key Laboratory of Oceanic Information Perception and Intelligent Processing School of Ocean Information EngineeringJimei UniversityXiamen 361021China College of Chemistry Fuzhou UniversityFuzhou 350108China State Key Laboratory of Physical Chemistry of Solid Surfaces MOE Key Laboratory of Spectrochemical Analysis and InstrumentationiChEMCollege of Chemistry and Chemical EngineeringCollege of MaterialsCollege of EnergyXiamen UniversityXiamen 361005China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China Shenzhen Research Institute of Xiamen University Shenzhen 518000China

The composition and evolution of interfacial species play a key role during electrocatalytic *** the structural evolution and intermediate during catalytic process by in situ characterization can shed new light on the electrocatalytic reaction mechanism and develop highly efficient ***,directly probing the interfacial species is extremely difficult for most spectroscopic techniques due to complicated interfacial environment and ultra-low surface ***,electrochemical core-shell nanoparticle enhanced Raman spectroscopy is utilized to probe the composition and evolution processes of interfacial species on Au@Pt,Au@Co,and Au@PtCo core-shell nanoparticle *** spectral evidences of interfacial intermediates including hydroxide radical(OH*),superoxide ion(O_(2)^(−)),as well as metal oxide species are directly captured by in situ Raman spectroscopy,which are further confirmed by the both isotopic experiment and density functional theory *** results provide a mechanistic guideline for the rational design of highly efficient electrocatalysts.

关键词： in situ Raman core-shell nanoparticle PtCo interfacial species composition and evolution

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Efficient removal of Cr(VI) by polydopamine-modified lignin from aqueous solution: Batch and XAFS studies

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Water Science and Engineering 2024年第1期17卷 51-61页

作者： Xiao-jie Guo wei-kang Fu jing-yuan Ma Bo-jun Xi Chen Wang Meng-yao Guan College of Materials and Environmental Engineering Hangzhou Dianzi UniversityHangzhou 310018China College of Textile and Garment Shaoxing UniversityShaoxing 312000China Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China

Lignocellulose has the potential to become a bio-based adsorbent due to its biodegradability and *** this study,a novel polydopamine functionalized-lignin(lignin@PDA),prepared via self-polymerization of dopamine(PDA)on lignin,was used as a bio-based adsorbent for rapid scavenging of hexavalent chromium(Cr(VI)).The morphology,functional groups,crystalline structure,and chemical composition of lignin@PDA were characterized with a scanning electron microscope-energy dispersive spectrometer,Fourier transform infrared spectroscopy,X-ray diffraction,and X-ray photoelectron *** Cr(VI)adsorption process of lignin@PDA was studied using batch experiments as a function of pH,ionic strength,adsorbent dose,and contact time at room *** adsorption rate of lignin@PDA was five times greater than that of the unmodified lignin,with a maximum adsorption capacity of 102.6 mg/g in an acidic *** adsorption of Cr(VI)on lignin@PDA fit the pseudo-secondorder equation and the Freundlich model,indicating that the adsorption process was mainly dominated by chemisorption and surface *** thermodynamic parameters showed that adsorption of Cr(VI)on lignin@PDA was an endothermic and spontaneous *** X-ray absorption fine structure results showed that sorption and reduction of Cr(VI)into Cr(II)occurred simultaneously on ***,PDA coating not only improved the reactivity of lignin but also promoted the complete reduction of Cr(VI)by *** to these results,polydopamine functionalized-lignin is a promising bio-based adsorbent for immobilization of Cr(VI)from wastewater.

关键词： Lignin Polydopamine Hexavalent chromium EXAFS Adsorption mechanism

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Total Synthesis and Stereochemical Assignment of Talaroconvolutin A and Talarofuranone: Gram-scale Synthesis of Ferroptosis Inducer Talaroconvolutin A

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Chinese Journal of Chemistry 2024年第13期42卷 1509-1514页

作者： Ming yao wei Yang jing Li Chengyun Huang Jin Fang Sulu Qin Shuzhi Liu Xiaolong Yang School of Pharmaceutical Sciences South-Central Minzu UniversityWuhanHubei 430074China

The first total synthesis of talaroconvolutin A(1.1 g obtained)and talarofuranone has been achieved using accessible materials(12 steps,7.5%and 8.2%yields,respectively).Convergent routes involved intramolecular Diels-Alder reactions in two approaches for creating the decalin ***,an unprecedented DMP-mediated domino reaction resulted in the deoxy-tetramic acid *** syntheses not only establish the absolute configuration of talaroconvolutin A but also enable further collaborative studies of this typeofferroptosisinducers.

关键词： Natural products Aldehydes Total synthesis Domino reactions Biological activity Antitumor agents Ferroptosis Diels-Alder reaction Talaroconvolutin A

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The influence of corneal ablation patterns on prediction error after cataract surgery in post-myopic-LASIK eyes

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Eye and Vision 2024年第4期10卷 23-31页

作者： Yunqian yao jing Zhao Jifeng Yu Wenwen He Ling wei Xingtao Zhou Yi Lu Xiangjia Zhu Eye Institute and Department of Ophthalmology Eye&ENT HospitalFudan University83 Fenyang RoadShanghai 200031China National Health Center Key Laboratory of Myopia(Fudan University) Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina Shanghai Key Laboratory of Visual Impairment and Restoration ShanghaiChina Shanghai Research Center of Ophthalmology and Optometry ShanghaiChina Department of Ophthalmology Beijing Children's HospitalNational Center for Children's HealthCapital Medical UniversityBeijingChina State Key Laboratory of Medical Neurobiology Fudan UniversityShanghaiChina

Purpose:To evaluate the influence of corneal ablation patterns on the prediction error after cataract surgery in postmyopic-LASIK ***:Eighty-three post-myopic-LASIK eyes of 83 patients that underwent uneventful cataract surgery were retrospectively *** postoperative spherical equivalence(SE)was calculated for the implanted lens using the Haigis-L and Barrett True-K *** error at one month postsurgery was calculated as actual SE minus predicted *** each eye,area and decentration of the ablation zone was measured using the tangential curvature *** associations between prediction errors and corneal ablation patterns were ***:The mean prediction error was-0.83±1.00 D with the Haigis-L formula and-1.00±0.99 D with the Barrett True-K *** error was positively correlated with keratometry(K)value and negatively correlated with ablation zone area using either formula,and negatively correlated with decentration of the ablation zone using the Barrett True-K formula(all P<0.05).In the K<37.08 D group,prediction error was negatively correlated with decentration of the ablation zone with both formulas(all P<0.05).Multivariate analysis showed that with the Haigis-L formula,prediction error was associated with axial length(AL),K value and decentration,and with the Barrett True-K formula,prediction error was associated with AL and decentration(all P<0.05).Conclusion:A flatter cornea,larger corneal ablation zone and greater decentration will lead to more myopic prediction error after cataract surgery in post-myopic-LASIK eyes.

关键词： Cataract surgery Laser in situ keratomileusis Intraocular lens power Keratometry Ablation zone decentration Ablation zone size

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