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Integrative analyses identified gap junction beta‐2 as a prognostic biomarker and therapeutic target for breast cancer

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Cancer Innovation 2024年第4期3卷 43-56页

作者： di Zhang Lixi Li Fei ma Department of Medical Oncology Qilu Hospital of Shandong UniversityJinanChina Department of Medical Oncology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background:Increasing evidence has shown that connexins are involved in the regulation of tumor development,immune escape,and drug *** study investigated the gene expression patterns,prognostic values,and potential mechanisms of connexins in breast ***:We conducted a comprehensive analysis of connexins using public gene and protein expression databases and clinical samples from our *** mRNA expressions in breast cancer and matched normal tissues were compared,and multiomics studies were ***:Gap junction beta‐2 mRNA was overexpressed in breast cancers of different pathological types and molecular subtypes,and its high expression was associated with poor *** tumor membrane of the gap junction beta‐2 mutated group was positive,and the corresponding protein was *** mutation and copy number variation of gap junction beta‐2 are rare in breast *** gap junction beta‐2 transcription level in the p110αsubunit of the phosphoinositide 3‐kinase mutant subgroup was higher than that in the wild‐type *** junction beta‐2 was associated with the phosphoinositide 3‐kinase‐Akt signaling pathway,extracellular matrix–receptor interaction,focal adhesion,and proteoglycans in ***,gap junction beta‐2 overexpression may be associated with phosphoinositide 3‐kinase and histone deacetylase inhibitor resistance,and its expression level correlated with infiltrating CD8+t cells,macrophages,neutrophils,and dendritic ***:Gap junction beta‐2 may be a promising therapeutic target for targeted therapy and immunotherapy and may be used to predict breast cancer prognosis.

关键词： breast cancer connexin gap junction beta‐2 phosphoinositide 3‐kinase‐Akt‐mtOR pathway prognosis

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Neural Network Robust Control Based on Computed torque for Lower Limb Exoskeleton

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 83-99页

作者： Yibo Han Hongtao ma Yapeng Wang di Shi Yanggang Feng Xianzhong Li Yanjun Shi Xilun ding Wuxiang Zhang School of Mechanical Engineering and Automation Beihang UniversityBeijing 100191China Beihang Goer(WeiFang)Intelligent Robot Co. Ltd.Beihang UniversityWeifangChina Research Center of Satellite technology Harbin Institute of TechnologyHarbinChina Beijing Xinfeng Aerospace Equipment Co. LtdBeijingChina

the lower limb exoskeletons are used to assist wearers in various scenarios such as medical and industrial *** modeling errors of the exoskeleton in different application scenarios pose challenges to the robustness and stability of its control *** Radial Basis Function(RBF)neural network is used widely to compensate for modeling *** order to solve the problem that the current RBF neural network controllers cannot guarantee the asymptotic stability,a neural network robust control algorithm based on computed torque method is proposed in this paper,focusing on trajectory *** innovatively incorporates the robust adaptive term while introducing the RBF neural network term,improving the compensation ability for modeling *** stability of the algorithm is proved by Lyapunov method,and the effectiveness of the robust adaptive term is verified by the *** wearing the exoskeleton under different walking speeds and scenarios were carried out,and the results show that the absolute value of tracking errors of the hip and knee joints of the exoskeleton are consistently less than 1.5°and 2.5°,*** proposed control algorithm effectively compensates for modeling errors and exhibits high robustness.

关键词： Lower limb exoskeleton Model compensation RBF neural network Computed torque method

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Role of toll-like receptor 4/mutant myeloid differentiation primary response 88/nuclear factor kappa-B mediated inflammation in diabetes mellitus with Northwest dryness syndrome

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Journal of traditional Chinese Medicine 2024年第5期44卷 963-973页

作者： DENG Deqiang XIAO Yan ma Dan QIU Jinling HAO Congli WANG di ZHANG Miao State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Medical University Department of Endocrinology Traditional Chinese Medicine Hospital of Urumqi

OBJECtIVE: to investigate the role of toll-like receptor 4(tLR4)/mutant myeloid differentiation primary response 88(MyD88)/nuclear factor kappa-B(NF-κB) signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness ***: Rats were randomly divided into the normal control, type 2 diabetes(t2DM) model, Northwest dryness syndrome + t2DM(Northwest dryness), and simple internal dampness + t2DM(internal dampness)groups. Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory *** histopathological observation was *** real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels, ***: Compared with the t2DM group, the glycosylated hemoglobin A1c, insulin, glucose tolerance,the homeostasis model assessment of insulin resistance,tumor necrosis factor-α, interleukin 1β, interleukin 16,malondialdehyde, blood lipid, alanine aminotransferase,and aspartate aminotransferase were significantly elevated in the internal dampness group. their levels were significantly elevated in the Northwest dryness group than in the t2DM and internal dampness *** superoxide dismutase, glutathione peroxidase, liver glycogen, and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the t2DM ***, these levels were elevated in the Northwest dryness group than in the internal dampness ***, the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65, and the protein expression levels of tLR4, MyD88, and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the t2DM ***, the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness ***: Northwest dryness syndrome-mediated tLR4/MyD88/NF-κB pathway and chronic i

关键词： NF-kappa B Northwest dryness syndrome diabetes mellitus inflammation myeloid differentiation factor 88 toll-like receptor 4

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the Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory t Cells

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Research 2024年第2期2023卷 373-387页

作者： di Wu Yi Sun Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory t(t_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of t_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in t_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in t_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in t_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null t_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of t_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

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Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 273-286页

作者： di Pan Hao-Nan Liu Peng-Fei Qu Xiao ma Lu-Yao ma Xiao-Xiao Chen Yu-Qin Wang Xiao-Bing Qin Zheng-Xiang Han Department of Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina Department of Gastroenterology The Second Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina Department of General Surgery The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human *** to challenges in early diagnosis,most patients lose the opportunity for radical treatment when ***,recent advancements in cancer immunotherapy provide new directions for the treatment of *** instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with ***,tumor cells can evade the immune system through various *** the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor t cells,engineered cytokines,and certain cancer *** review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.

关键词： Hepatocellular carcinoma Immunotherapies Immune checkpoint inhibitor Clinical efficacy Adverse reactions

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Photoluminescence and ratiometric thermo-response of Eu^(2+)and Eu^(3+)in BaAl_(2)B_(2)O_(7):Eu^(2+),Eu^(3+)phosphor materials

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Journal of Rare Earths 2024年第7期42卷 1240-1249,I0002页

作者： Ziyao Wang Haitao Fu Xiufeng Zhan Bo tong Guofeng ma H.t.(Bert)Hintzen Institute of Innovative Science and technology Shenyang UniversityShenyang110044China College of Mechanical Engineering Shenyang UniversityShenyang110044China Faculty of Applied Sciences Delft University of Technology2629 JBDelftthe Netherlands

A novel Eu^(2+)-Eu^(3+)co-activated ratiometric thermo-sensitive phosphor was developed and synthesized by solid-state *** valence state of Eu,photoluminescence and thermo-sensitive performance of the phosphor prepared either in ambient air or carbothermally were investigated and *** phosphor shows high sensitivity(Sa=0.0173 K^(-1),S_(r)=0.461%/K)and superior signal discriminability(Δν∼10380 cm^(−1)).the thermo-sensitive performance is subject to the dual effects of different thermo-responses by Eu^(2+)versus Eu^(3+)combined with energy transfer from Eu^(2+)to Eu^(3+),so that the sensitivity of the phosphor in the temperature range presents a non-monotonic *** development of the BaAl_(2)B_(2)O_(7):Eu^(2+),Eu^(3+)phosphor is not only expected to be relevant for application in the field of temperature sensing,but also of reference significance for improving the sensitivity by means of energy transfer between co-activator ions over a wider temperature range of Eu^(2+)-Eu^(3+)co-activated ratiometric thermo-sensitive phosphors.

关键词： Photoluminescence Ratiometric thermo-response Phosphor Eu^(2+)/Eu^(3+) Rare earths

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Design method and experimental study of a cathode tool with an extremely high leveling ratio for electrochemical machining of blisk

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Chinese Journal of Aeronautics 2024年第4期37卷 593-608页

作者： Moqi SHEN Jia LIU Jingtao WANG di ZHU College of Mechanical and Electrical Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210016China

to obtain final parts with the desired dimensional accuracy and repeatability via electrochemical machining(ECM), the machining process must enter an ECM balanced state. However,for the ECM processing of blisk, a key component of aerospace engines, the surface of the blade blank often has an uneven allowance distribution due to the narrow passage of the cascade. It is difficult to remedy this issue in subsequent processing steps, which is necessary to ensure the dimensional accuracy and repeatability of the final blade profile. to solve this problem, electrolytic machining must be preceded by electrolytic shaping, which requires cathode tools with large leveling ratios to quickly homogenize the blank surface of the blade. In this study, to obtain a cathode tool with an extremely high leveling ratio, a design method based on the variation in the electrode gap in the non-equilibrium electrolytic state is proposed, and a dissolution model based on the nonequilibrium state is established. In this design method, the allowance on the blank to be machined is first divided into many discrete allowances with the normal direction. the initial machining clearance, feed rate, and total machining time are then calculated using classical ECM equilibrium state theory based on the maximum allowance. Meanwhile, the point coordinates of the cathode tool at maximum allowance can be determined. the non-equilibrium model can then be used to calculate the relative coordinate positions corresponding to the remaining discrete allowances. Finally, the entire cathode tool profile is designed. Simulations, fundamental experiments, and blisk unit workpiece experiments were carried out to validate the design approach. In the simulated processing of the plane workpiece, the leveling ratio of the cathode tool designed by the proposed method(0.77)was 83% higher than that of the cathode tool designed using the traditional method. the simulation results were confirmed by processing experiments. In t

关键词： Electrochemical machining(ECM) Non-equilibrium machining Large leveling ratios Cathode design Finite element simulation Blisk

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A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification

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traditional Medicine Research 2024年第2期9卷 27-41页

作者： Peng-Yu Wang Jian-Fen Shen Shuo Zhang Qing Lan Guan-di ma tong Wang You-Zhi Zhang School of Pharmacy Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei ProvinceXianning Medical CollegeHubei University of Science and TechnologyXianning 437100China Department of Central Laboratory The First Affiliated Hospital of Jiaxing UniversityJiaxing 314000China

Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(the clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized ***,the mechanism of EZECD on damp-heat internalized type 2 diabetes(t2D)remains *** employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized ***:the main compounds or genes of EZECD and damp-heat internalized t2D were obtained from the pharmacology ***,the overlapped targets of EZECD and damp-heat internalized t2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes *** the compound-disease targets-pathway network were constructed to obtain the hub ***,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock ***,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized ***,the interactions of hub compound and genes were explored using Comparative toxicogenomics Database and quantitative polymerase chain ***:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized t2D could be ***,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network *** docking showed that quercetin could bind with the hub ***,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the tNF or lipopolysaccharide process,and AHR or CCL2 positively regulated li

关键词： data mining damp-heat internalized type 2 diabetes Erzhu Erchen decoction network pharmacology bioinformatics

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Supported Recyclable Metal-free Frustrated Lewis Pair Catalyst for Catalytic Hydrogenation of Substituted Pyridines to Piperidines

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Chemical Research in Chinese Universities 2024年第4期40卷 682-689页

作者： ma Shaohua tANG Zhiyong CAS Key Laboratory for Nanosystem and Hierarchical Fabrication CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing100190P.R.China University of Chinese Academy of Sciences Beijing100049P.R.China

the construction of heterogeneous frustrated Lewis pairs(FLPs)catalysts is crucial for realizing highly efficient and recyclable pyridines catalytic *** this work,we prepared a recyclable heterogenous FLPs catalyst CMP-BF with conjugated microporous polymer CMP-ethynyl as the support via self-catalyzed 1,1-carboboration reaction with commercial Lewis acid B(C_(6)F_(5))_(3).the as-synthesized CMP-BF demonstrates superior heterogenous catalytic hydrogenation performance(conversion>99%),and considerable stability(84%conversion after three cycles)in recyclable hydrogenation of 2,*** work provides insights into the fabrication and catalytic application of recyclable heterogenous FLP catalysts.

关键词： Pyridine hydrogenation Frustrated Lewis pair Conjugated microporous polymer

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Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

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World Journal of Gastroenterology 2024年第17期30卷 2294-2297页

作者： Fabiola di Dato Raffaele Iorio Department of translational Medical Science Section of PediatricsUniversity of Naples Federico IINaples 80131Italy

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular *** the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis ***,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the *** are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment *** editorial addresses key questions about the topic and whether indications for treatment should be expanded.

关键词： Hepatitis B virus Interferon Nucleos(t)ide analogues Functional cure Children

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