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Inhibition of Eukaryotic Initiating Factor eIF4E Overcomes Abemaciclib Resistance in Gastric Cancer

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Current Medical Science 2023年第5期43卷 927-934页

作者： Huo-long ZHA wei CHEN wei SHI ying-ying LIAO Department of Gastroenterology Renmin HospitalHubei University of MedicineShiyan 442000China Department of Critical Care Medicine Taihe HospitalHubei University of MedicineShiyan 442000China

Objective Aberrant activating mutations in cyclin-dependent kinases 4 and 6(CDK4/6)are common in various cancers,including gastroesophageal malignancies.Although CDK4/6 inhibitors,such as abemaciclib and palbociclib,have been approved for breast cancer treatment,their effectiveness as a monotherapy remains limited for gastroesophageal tumors.The present study explored the underlying mechanism of abemaciclib resistance.Methods Abemaciclib-resistant gastric cancer cell lines were generated,and the phospho-eukaryotic translation initiation factor 4E(p-eIF4E)and eIF4E expression was compared between resistant and parental cell lines.In order to analyze the role of eIF4E in cell resistance,siRNA knockdown was employed.The effectiveness of ribavirin alone and its combination with abemaciclib was evaluated in the gastric cancer xenograft mouse model.Results The upregulation of eIF4E was a common feature in gastric cancer cells exposed to prolonged abemaciclib treatment.Gastric cancer cells with increased eIF4E levels exhibited a better response to eIF4E inhibition,especially those that were resistant to abemaciclib.Ribavirin,which is an approved anti-viral drug,significantly improved the efficacy of abemaciclib,both in vitro and in vivo,by inhibiting eIF4E.Importantly,ribavirin effectively suppressed the abemaciclib-resistant gastric cancer growth in mice without causing toxicity.Conclusion These findings suggest that targeting eIF4E can enhance the abemaciclib treatment for gastric cancer,proposing the potential combination therapy of CDK4/6 inhibitors with ribavirin for advanced gastric cancer.

关键词： eIF4E CDK4/6 ribavirin gastric cancer resistance

Ce-promoted Mn/ZSM-5 catalysts for highly efficient decomposition of ozone

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Journal of Environmental Sciences 2021年第5期33卷 219-228页

作者： Linlin wei Hongxia Chen Ying Wei Jingbo Jia Runduo Zhang State Key Laboratory of Chemical Resource Engineering Beijing Key Laboratory of Energy Environmental CatalysisBeijing University of Chemical TechnologyBeijing 100029PR China

Manganese oxides supported by ZSM-5 zeolite(Mn/ZSM-5) as well as their further modified by Ce promoter were achieved by simple impregnation method for ozone catalytic decomposition. The yCe20Mn/ZSM-5–81 catalyst with 8% Ce loading showed the highest catalytic activity at relative humidity of 50% and a space velocity of 360 L/(g × hr), giving 93% conversion of 600 ppm O_(3) after 5 hr. Moreover, this sample still maintained highly activity and stability in humid air with 50%–70% relative humidity. Series of physicochemical characterization including X-ray diffraction, temperature-programmed technology(NH_3-TPD and H_(2)-TPR), X-ray photoelectron spectroscopy and oxygen isotopic exchange were introduced to disclose the structure-performance relationship. The results indicated that moderate Si/Al ratio(81) of zeolite support was beneficial for ozone decomposition owing to the synergies of acidity and hydrophobicity. Furthermore, compared with 20 Mn/ZSM-5-81, Ce doping could enhance the amount of low valance manganese(such as Mn^(2+) and Mn^(3+)). Besides, the Ce^(3+)/Ce^(4+) ratio of 8Ce20Mn/ZSM-5-81 sample was higher than that of 4Ce_(2)0 Mn/ZSM-5-81. Additionally, the synergy between the MnO_x and CeO_(2) could easily transfer electron via the redox cycle, thus resulting in an increased reducibility at low temperatures and high concentration of surface oxygen. This study provides important insights to the utilization of porous zeolite with high surface area to disperse active component of manganese for ozone decomposition.

关键词： Manganese oxide ZSM-5 zeolite Ce promoter Adsorbed oxygen Ozone decomposition

UFMylation:A Unique & Fashionable Modification for Life

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 140-146页

作者： Ying Wei Xingzhi Xu Beijing Key Laboratory of DNA Damage Response and College of Life Sciences Capital Normal University

Ubiquitin-fold modifier 1（UFM1） is one of the newly-identified ubiquitin-like proteins.Similar to ubiquitin,UFM1 is conjugated to its target proteins by a three-step enzymatic reaction.The UFM1-activating enzyme,ubiquitin-like modifier-activating enzyme 5（UBA5）,serves as the E1 to activate UFM1;UFM1-conjugating enzyme 1（UFC1） acts as the E2 to transfer the activated UFM1 to the active site of the E2;and the UFM1-specific ligase 1（UFL1） acts as the E3 to recognize its substrate,transfer,and ligate the UFM1 from E2 to the substrate.This process is called ufmylation.UFM1 chains can be cleaved from its target proteins by UFM1-specific proteases（Uf SPs）,suggesting that the ufmylation modification is reversible.UFM1 cascade is conserved among nearly all of the eukaryotic organisms,but not in yeast,and associated with several cellular activities including the endoplasmic reticulum stress response and hematopoiesis.Furthermore,the UFM1 cascade is closely related to a series of human diseases.In this review,we summarize the molecular details of this reversible modification process,the recent progress of its functional studies,as well as its implication in tumorigenesis and potential therapeutic targets for cancer.

关键词： Ubiquitin-fold modifier 1 Ufmylation Endoplasmic reticulum stress Cancer Post-translation modification Ubiquitin-like proteins

Hierarchical Cluster Coordination Control Strategy for Large-scale Wind Power Based on Model Predictive Control and Improved Multi-time-scale Active Power Dispatching

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Journal of Modern Power Systems and Clean Energy 2023年第3期11卷 827-839页

作者： ying Zhu Yanan Zhang Zhinong wei College of Energy and Electrical Engineering Hohai UniversityNanjing 210098China

The grid-connection of large-scale and high-penetration wind power poses challenges to the friendly dispatching control of the power system.To coordinate the complicated optimal dispatching and rapid real-time control,this paper proposes a hierarchical cluster coordination control(HCCC)strategy based on model predictive control(MPC)technique.Considering the time-varying characteristics of wind power generation,the proposed HCCC strategy constructs an improved multitime-scale active power dispatching model,which consists of five parts:formulation of cluster dispatching plan,rolling modification of intra-cluster plan,optimization allocation of wind farm(WF),grouping coordinated control of wind turbine group(WTG),and real-time adjustment of single-machine power.The time resolutions are sequentially given as 1 hour,30 min,15 min,5 min,and 1 min.In addition,a combined predictive model based on complete ensemble empirical mode decomposition with adaptive noise(CEEMDAN),wavelet thresholding(WT),and least squares support vector machine(LSSVM)is established.The fast predictive feature of this model cooperates with the HCCC strategy that effectively improves the predictive control precision.Simulation results show that the proposed HCCC strategy enables rapid response to active power control(APC),and significantly improves dispatching control accuracy and wind power accommodation capabilities.

关键词： Wind power active power dispatching model predictive control(MPC) hierarchical control wind power prediction

N/Ce doped graphene supported Pt nanoparticles for the catalytic oxidation of formaldehyde at room temperature

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Journal of Environmental Sciences 2023年第3期125卷 135-147页

作者： Yaodong Guo Zhaoying Di Xiaonan Guo Ying Wei Runduo Zhang Jingbo Jia State Key Laboratory of Chemical Resource Engineering Beijing Key Laboratory of Energy Environmental CatalysisBeijing University of Chemical TechnologyBeijing 100029China

Pt catalysts with nitrogen-doped graphene oxide (GO) as support and CeO_(2)as promoter were prepared by impregnation method,and their catalytic oxidation of formaldehyde (HCHO) at room temperature was tested.The Pt-CeO_(2)/N-rGO (reduced GO) with a mass fraction of 0.7% Pt and 0.8%CeO_(2)exhibited an excellent catalytic performance with the 100% conversion of HCHO at room temperature.Physicochemical characterization demonstrated that nitrogendoping greatly increased the defect degree and the specific surface area of GO,enhanced the dispersion of Pt and promoted more zero-valent Pt.The synergistic effect between CeO_(2)and Pt was also beneficial to the dispersion of Pt.Nitrogen-doping promoted the production of more Ce3+ions,generating more oxygen vacancies,which was conducive to O_(2)adsorption.As a result,the catalyst exhibited enhanced redox properties,leading to the best catalytic activity.Finally,an attempt to propose the reaction mechanism of HCHO oxidation has been made.

关键词： Formaldehyde N-doped graphene oxide Pt catalyst Room temperature

Anomalies of Precipitation over China on Days with Tropical Cyclone Activity over the Bay of Bengal: Role of Moisture Transport

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Journal of Meteorological Research 2024年第2期38卷 368-382页

作者： Na wei ying LI Xiaoting FAN Nanjing Joint Institute for Atmospheric Sciences Nanjing 210041 State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081 Department of Atmospheric and Oceanic Sciences and Institute of Atmospheric Sciences Fudan UniversityShanghai 200433

Tropical cyclones over the Bay of Bengal(BoBTC)affect the precipitation over China,with distinct seasonal and daily variabilities.This study quantitatively examines the daily standardized precipitation anomalies(SPAs)over China on the days with BoBTC activities(storm-days)and related circulations,based on rainfall measurements at surface meteorological stations and ECMWF reanalysis data on a 0.25°×0.25°resolution during 1979-2019.Significant positive SPA is found over the stations in the two adjacent regions around BoB(Southwest China in May/November and southern Tibetan Plateau in October)and three distant regions(Southeast China and the northeastern boundary of the Qinghai-Tibet Plateau in May,and central North China in October).The SPA distributions are remarkably consistent with the integrated water vapor transport(IVT)anomalies.Enhanced IVT is found associated with the interaction between southwesterly(southerly)of the BoBTC circulation and low-level monsoonal flow in May(midlevel westerly in winter months).The probabilities of extreme precipitation(EP)occurrences over the above regions all increase on storm-days.For adjacent regions,EP is significantly correlated with the northward IVT anomalies to the east of BoBTC circulation,which strengthen the water vapor input through the southern border.Such IVT anomalies are stronger in May,benefited by the deep monsoonal southwesterlies than those in November.For distant regions,EP is more closely related to the IVT anomaly extending back from BoB.Enhanced moisture from BoB concentrates along a local low-level convergence line over Southeast China,being further facilitated by coexistence of the BoBTC depression and midlevel westerly trough in midlatitudes.Our results highlight the interactions between BoBTCs and local weather systems that influence the general precipitation anomalies and occurrence of EP over China,especially over distant regions.

关键词： tropical cyclone Bay of Bengal precipitation anomaly moisture transport

DPP-4 inhibitors and GLP-1RAs:cardiovascular safety and benefits

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Military Medical Research 2023年第2期10卷 227-241页

作者： Michael Razavi ying-Ying Wei Xiao-Quan Rao Ji-Xin Zhong Tulane University School of Medicine New OrleansLA 70112USA Department of Rheumatology and Immunology Tongji HospitalTongji Medical College of Huazhong University of Science and Technology1095 Jiefang AveWuhan 430032China Department of Cardiovascular Medicine Tongji HospitalTongji Medical College of Huazhong University of Science and Technology1095 Jiefang AveWuhan 430032China Institute of Allergy and Clinical Immunology Tongji HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhan 430032China

Glucagon-like peptide-1 receptor agonists(GLP-1RAs)and dipeptidyl peptidase-4 inhibitors are commonly used treatments for patients with type 2 diabetes mellitus(T2DM).Both anti-diabetic treatments function by playing key modulatory roles in the incretin system.Though these drugs have been deemed effective in treating T2DM,the Food and Drug Administration(FDA)and some members of the scientific community have questioned the safety of these therapeutics relative to important cardiovascular endpoints.As a result,since 2008,the FDA has required all new drugs for glycemic control in T2DM patients to demonstrate cardiovascular safety.The present review article strives to assess the safety and benefits of incretin-based therapy,a new class of antidiabetic drug,on the health of patient cardiovascular systems.In the process,this review will also provide a physiological overview of the incretin system and how key components function in T2DM.

关键词： Glucagon-like peptide-1 receptor agonists Dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Cardiovascular outcome

Recent advances in neutrophil chemotaxis abnormalities during sepsis

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Chinese Journal of Traumatology 2022年第6期25卷 317-324页

作者： Yu-ying Zhou Bing-wei Sun Department of Burns and Plastic Surgery Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215002Jiangsu ProvinceChina

Sepsis remains one of the leading causes of death globally,in spite of advanced developments in intensive care and better understandings of pathophysiology related to sepsis.There is no special treatment or drug available for sepsis,currently.Under normal circumstances,neutrophil is a major player in acute infection control.However,during sepsis,the migration abilities and antimicrobial functions of neutrophils are impaired,resulting in a dysregulated immune response.Recent studies have indeed demonstrated that blocking or reversing neutrophil migration and impaired antibacterial function can improve the outcomes in septic animal models.This article systemically synthesized information regarding related factors and signaling involved in the functions of neutrophils in sepsis.This review also discussed the possibility that neutrophils be used as a marker for specific diagnosis and/or prediction of the outcomes of sepsis.

关键词： Sepsis Neutrophil Chemotaxis Dysfunction Migration

One-Pot Synthesis of Spiro[fluorene-9,9'-xanthene]Derivatives

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Chinese Journal of Chemistry 2021年第3期39卷 701-709页

作者： Hao-Xuan Yuan Ying Wei Ling-Hai Xie wei Huang Centre for Molecular Systems and Organic Devices(CMSOD)&Key Laboratory for Organic Electronics and Information Displays&Institute of Advanced Materials(IAM)&Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM) Nanjing University of Posts&Telecommunications9 Wenyuan RoadNanjingJiangsu 210023China Shaanxi Institute of Flexible Electronics(SIFE) Northwestern Polytechnical University127 West Youyi RoadXi'anShaanxi 710072China

As a novel class of spirofluorenes,spirobifluorene(SBF)and spiro[fluo-rene-9,9'-xanthene]derivatives(SFXs)have orthogonal geometric config-uration,spiro-conjugation effect,and rigid steric hindrance,which can be widely used in the fields of synthetic chemistry,materials chemistry and supramolecular chemistry.Due to their facile one-pot synthetic route,and to the variety of molecular designs,SFXs are expected to become new spiro functional materials that replace SBF.In this review,we present the history,development and expansion of SFXs synthesis in one-pot methods,and the advantages and limitations of one-pot synthesis are also dis-cussed.

关键词： Spirofluorenes Spiro[fluorene 9,9'-xanthene]s(SFXs) One pot synthesis Synthetic methods Heterocycles Cyclization