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Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice

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Chinese Journal of Integrative Medicine 2019年第12期25卷 902-910页

作者： zheng zhi-yin YU Xiao-ling DAI Tie-ying yin Li-ming ZHAO Yan-na XU Min ZHUANG Hai-feng Chong Beng Hock GAO Rui-lan Institution of Hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou(310006)China Department of Hematology St George HospitalSt George Clinical SchoolUniversity of New South WalesKogarah(NSW 2217)Australia

Objective: To investigate the potential efficacy of panaxadiol saponins component(PDS-C) in the treatment of aplastic anemia(AA) model mice. Methods: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C(20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine(40 mg/kg), and andriol(25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and Fox P3 proteins were detected by flow cytometry and Western blot. Results: The peripheral blood of white blood cell(WBC), platelet, neutrophil counts and hemoglobin(Hb) concentration were significantly decreased in the model group compared with the normal group(all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group(all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers(all P<0.01). Furthermore,PDS-C therapy increased peripheral blood CD3^+ and CD3^+CD4^+ cells and reduced CD3^+CD8^+ cells(P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium-and high doses groups also increase

关键词： Panaxadiol saponins component aplastic anemia hematopoiesis T lymphocyte

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Variational Analysis Based on Proximal Subdifferential on Smooth Banach Spaces

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Acta Mathematica Sinica,English Series 2024年第2期40卷 595-618页

作者： Xi yin zheng Department of Mathematics Yunnan UniversityKunming 650091P.R.China

This paper first shows that for any p∈(1,2)there exists a continuously differentiable function f on l^(p)(and L^(p))such that the proximal subdifferential of f is empty everywhere,and hence it is not suitable to develop theory on proximal subdifferential in the classical Banach spaces l^(P)and L^(P) with p∈(1,2).On the other hand,this paper establishes variational analysis based on the proximal subdifferential in the framework of smooth Banach spaces of power type 2,which conclude all Hilbert spaces and all the classical spaces l^(P)and L^(P)with p∈(2,+∞).In particular,in such a smooth space,we provide the proximal subdifferential rules for sum functions,product functions,composite functions and supremum functions,which extend the basic results on the proximal subdifferential established in the framework of Hilbert spaces.Some of our main results are new even in the Hilbert space case.As applications,we provide KKT-like conditions for nonsmooth optimization problems in terms of proximal subdifferential.

关键词： Smooth Banach space proximal subdifferential proximal normal cone KKT condition

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AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

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Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng yin Shunzi Jin Baisong zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of Virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of Radiobiology(Jilin University) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to TME.This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of hepatoma.Methods:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and H22.The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab group.Cytotoxic CD8^(+)T cells in TME were analyzed by flow cytometry.Results:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro.AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage.AZD1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft mice.Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells depletion.Conclusions:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improv

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage Tumor microenvironment

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A robust tensor watermarking algorithm for diffusion-tensor images

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Frontiers of Information Technology & Electronic Engineering 2024年第3期25卷 384-397页

作者： Chengmeng LIU zhi LI Guomei WANG Long zheng State Key Laboratory of Public Big Data College of Computer Science and TechnologyGuizhou UniversityGuiyang 550025China

Watermarking algorithms that use convolution neural networks have exhibited good robustness in studies of deep learning networks.However,after embedding watermark signals by convolution,the feature fusion eficiency of convolution is relatively low;this can easily lead to distortion in the embedded image.When distortion occurs in medical images,especially in diffusion tensor images(DTIs),the clinical value of the DTI is lost.To address this issue,a robust watermarking algorithm for DTIs implemented by fusing convolution with a Transformer is proposed to ensure the robustness of the watermark and the consistency of sampling distance,which enhances the quality of the reconstructed image of the watermarked DTIs after embedding the watermark signals.In the watermark-embedding network,Ti-weighted(Tlw)images are used as prior knowledge.The correlation between T1w images and the original DTI is proposed to calculate the most significant features from the T1w images by using the Transformer mechanism.The maximum of the correlation is used as the most significant feature weight to improve the quality of the reconstructed DTI.In the watermark extraction network,the most significant watermark features from the watermarked DTI are adequately learned by the Transformer to robustly extract the watermark signals from the watermark features.Experimental results show that the average peak signal-to-noise ratio of the watermarked DTI reaches 50.47 dB,the diffusion characteristics such as mean diffusivity and fractional anisotropy remain unchanged,and the main axis deflection angleαAc is close to 1.Our proposed algorithm can effectively protect the copyright of the DTI and barely affects the clinical diagnosis.

关键词： Robust watermarking algorithm Transformer Image reconstruction Diffusion tensor images Soft attention Hard attention Tl-weighted images

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Mechanism Design for Ancillary Service Market Considering Social Welfare and Fairness

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1000-1010页

作者： zhi Wu Yuanxi Wu Wei Gu zheng Xu Shu zheng Jingtao Zhao School of Electrical Engineering Southeast UniversityNanjing 210096China NARI Technology Co. Ltd.Nanjing 211106China IEEE CSEE

Increasing penetration of distributed energy resources in the distribution network(DN)is threatening safe operation of the DN,which necessitates setup of the ancillary service market in the DN.In the ancillary service market,distribution system operator(DSO)is responsible for safety of the DN by procuring available capacities of aggregators.Unlike existing studies,this paper proposes a novel market mechanism composed of two parts:choice rule and payment rule.The proposed choice rule simultaneously considers social welfare and fairness,encouraging risk-averse aggregators to participate in the ancillary service market.It is then formulated as a linear programming problem,and a distributed solution using the multi-cut Benders decomposition is presented.Moreover,successful implementation of the choice rule depends on each aggregator’s truthful adoption of private parameters.Therefore,a payment rule is also designed,which is proved to possess two properties:incentive compatibility and individual rationality.Simulation results demonstrate effectiveness of the proposed choice rule on improving fairness and verify properties of the payment rule.

关键词： Aggregator ancillary service market distributed mechanism fairness mechanism design

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In-situ AFM and quasi-in-situ studies for localized corrosion in Mg-9Al-1Fe-(Gd) alloys under 3.5 wt.% NaCl environment

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Journal of Magnesium and Alloys 2024年第3期12卷 1170-1185页

作者： Junping Shen Tao Lai zheng yin Yang Chen Kun Wang Hong Yan Honggun Song Ruiliang Liu Chao Luo zhi Hu School of Advanced Manufacturing Nanchang UniversityNanchang 330031China Institute for Advanced Study Nanchang UniversityNanchang 330031China Singapore Centre for Environmental Life Sciences Engineering Nanyang Technological University60 Nanyang Drive 637751Singapore

Revealing the localized corrosion process of Mg alloy is considered as one of the most significant ways for improving its corrosion resistance.The reliable monitor should be high distinguishability and real-time in liquid environment.Herein,Mg-9Al-1Fe and Mg-9Al-1Fe-1Gd alloys were designed to highlight the impact of intermetallic on the corrosion behaviour.In-situ AFM with a special electrolyte circulation system and quasi-in-situ SEM observation were used to monitor the corrosion process of the designed alloys.SEM-EDS and TEM-SAED were applied to identify the intermetallic in the designed alloys,and their volta potentials were measured by SKPFM.According to the real-time and real-space in-situ AFM monitor,the corrosion process consisted of dissolution of anodicα-Mg phase,accumulation of corrosion products around cathodic phase and shedding of some fine cathodic phase.Then,the localized corrosion process of Mg alloy was revealed combined with the results of the monitor of corrosion process and Volta potential difference.

关键词： Magnesium Localized corrosion In-situ AFM SKPFM Corrosion behaviour.

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Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate

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Defence Technology（防务技术） 2024年第2期32卷 222-231页

作者： Haotian Jian Guoqiang zheng Lejian Chen zheng Ning Guofu yin Peng Zhu Ruiqi Shen School of Chemistry and Chemical Engineering Nanjing University of Science and TechnologyNanjing 210094China Micro-Nano Energetic Devices Key Laboratory of MIIT Nanjing University of Science and TechnologyNanjing 210094China Anhui Province Key Laboratory of Microsystem the 43rd Research Institute of CETCHefei 230088China Science and Technology on Applied Physical and Chemistry Laboratory Shanxi Applied Physics and Chemistry Research Institute Xi'an 710061China

Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.

关键词： Exploding foil initiator PDV Plasma spectrum Ignition mechanism Boron potassium nitrate

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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-zhi Yu Man Liu zheng-Rui Bian Bei-Bei Zhang Qian Yu yin-Hai Xu Ren-Xian Tang Kui-Yang zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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Effect of solvent on the initiation mechanism of living anionic polymerization of styrene:A computational study

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Chinese Journal of Chemical Engineering 2024年第5期69卷 135-142页

作者： Shen Li yin-Ning Zhou Zhong-Xin Liu zheng-Hong Luo School of Chemical Engineering and Technology Hainan UniversityHaikou 570228China Department of Chemical Engineering School of Chemistry and Chemical EngineeringState Key Laboratory of Metal Matrix CompositesShanghai Jiao Tong UniversityShanghai 200240China

For living anionic polymerization(LAP),solvent has a great influence on both reaction mechanism and kinetics.In this work,by using the classical butyl lithium-styrene polymerization as a model system,the effect of solvent on the mechanism and kinetics of LAP was revealed through a strategy combining density functional theory(DFT)calculations and kinetic modeling.In terms of mechanism,it is found that the stronger the solvent polarity,the more electrons transfer from initiator to solvent through detailed energy decomposition analysis of electrostatic interactions between initiator and solvent molecules.Furthermore,we also found that the stronger the solvent polarity,the higher the monomer initiation energy barrier and the smaller the initiation rate coefficient.Counterintuitively,initiation is more favorable at lower temperatures based on the calculated results ofΔG_(TS).Finally,the kinetic characteristics in different solvents were further examined by kinetic modeling.It is found that in benzene and n-pentane,the polymerization rate exhibits first-order kinetics.While,slow initiation and fast propagation were observed in tetrahydrofuran(THF)due to the slow free ion formation rate,leading to a deviation from first-order kinetics.

关键词： Living anionic polymerization Solvent effect Reaction kinetics Computational chemistry Mathematical modeling Kinetic modeling

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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu yin Haiqing zheng Liying Zhang Xiquan Hu Department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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