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The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

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Genes & Diseases 2024年第3期11卷 452-467页

作者： Min wang Yixue Gu Qiubo li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang Department of Neurology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Department of Pediatrics Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Neurosurgery Affliated Hospital of Jining Medical UniversityJiningShandong 272000China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent *** lobe epilepsy(TLE)is one of the most common medically intractable seizure ***2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains *** this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of ***(Co-IP)/mass spectrometry(MS)was used to identify the potential *** Co-IP,we detected and confirmed the main potential TNIK *** fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)*** found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with ***-0846 delayed kindling progression and decreased seizure ***-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably ***-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and *** addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ *** results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

关键词： Epilepsy NCB-0846 Rat TLE TNIK Traf2-and NcK-interacting kinase

Synergistic Effect of Nitrogen/Phosphorus Co-Doping and Molybdenum Carbide Induced Electron Redistribution of Carbon Layer to Boost Hydrogen Evolution Reaction

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Chinese Journal of Chemistry 2024年第1期42卷 55-60页

作者： Jiamin Xiao Peng li Yanyan Sun Heng liu Javid Khan Handong Zhang Han Zhou Yaqiong Su Shuangyin wang Lei Han College of Materials Science and Engineering Hunan Joint International Laboratory of Advanced Materials and Technology for Clean EnergyHunan UniversityChangshaHunan 410082China School of Chemistry Engineering Research Center of Energy Storage Materials and Devices Ministry of EducationXi'an Key Laboratory of Sustainable Energy Materials ChemistryState Key Laboratory of Electrical Insulation and Power EquipmentXi'an Jiaotong UniversityXi'anShaanxi 710049China School of Materials Science and Engineering Central South UniversityChangshaHunan 410083China state Key Laboratory of Chem/Bio-Sensingand Chemometrics College of Chemistry and Chemical EngineeringHunan University ChangshaHunan 410082China Laboratory of Inorganic Materials and Catalysis Department of Chemical Engineering and ChemistryEindhoven University of Technology P.O.Box5135600 MB EindhovenThe Netherlands

The development of highly efficient non-precious-metal-based electrocatalysts for the hydrogen evolution reaction is imperative for promoting the large-scale application of electrochemical water ***,nitrogen/phosphorus co-doped carbon nanorods encapsulated Mo_(2)C nanoparticles(Mo_(2)C@PNc)have been prepared by pre-phosphating treatment in combination of the coordination with polydopamine and the subsequent *** phosphating temperature has a significant effect on the content of phosphorus within the resultant Mo_(2)C@PNC,and the optimal catalyst delivers superior HER activity with the low overpotential of 104 mV at a current density of 10 mAcm^(-2) and good stability for 8 h,which has been theoretically demonstrated to originate from the synergistic effect between P doping and Mo_(2)C induced electron redistribution of nitrogen-doped carbon layer.

关键词： Molybdenum carbide N/P co-doped carbon Hydrogen evolution Synergistic effect Electron redistribution Comprehensive

Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2999-3014页

作者： Yun Yang Qingya liu Meng wang Lang li Yan Yu Meng Pan Danrong Hu Bingyang Chu Ying Qu Zhiyong Qian Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens,including prolonged circulation in the bloodstream,specific cell recognition and targeting capabilities,and potential for ***,we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM *** microporous Prussian blue nanoparticles(MPB NPs)serving as both a photothermal sensitizer and carrier for 3-bromopyruvate(3BP),these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory proteinα(SIRPα)with enhanced affinity to *** a result,MPB-3BP@CM NPs inherit the characteristics of the original cell membrane,exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer(CRC)***,blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by ***,3BP,an inhibitor of hexokinase II(HK2),suppresses glycolysis,leading to a reduction in adenosine triphosphate(ATP)levels and lactate ***,it promotes the polarization of tumor-associated macrophages(TAMs)towards an anti-tumor M1 ***,integration with MPB NPs-mediated photothermal therapy(PTT)enhances the therapeutic efficacy against *** advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for ***,it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.

关键词： CD47 colorectal cancer

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Protein & Cell 2024年第7期15卷 530-546页

作者： Tao Chen Yiliang Xu Xiaocui Xu Jianzhang wang Zhiruo Qiu Yayuan Yu Xiaohong Jiang Wanqi Shao Dandan Bai Mingzhu wang Shuyan Mei Tao Cheng li Wu Shaorong Gao Xuan Che Department of Obstetrics and Gynecology Affiliated Women and Children Hospital of Jiaxing UniversityJiaxing 314000China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310013China Postgraduate training base Alliance of wenzhou Medical University Wenzhou Medical UniversityWenzhou 325035China Jiaxing University Master Degree Cultivation Base Zhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyClinical and Translational Research CenterShanghai First Maternity and Infant HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Adenomyosis is a poorly understood gynecological disorder lacking effective *** persists regarding“invagination”and“metaplasia”*** endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just *** single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and *** lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of ***,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin ***-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT *** study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

关键词： adenomyosis single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells

Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi wang Yaqi Zhang Danhua Zhu Lanjuan li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

Mg/Fe site-specific dual-doping to boost the performance of cobalt-free nickle-rich layered oxide cathode for high-energy lithium-ion batteries

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Journal of Energy Chemistry 2024年第4期91卷 670-679页

作者： Yunting wang Gaohui Du Di Han wenhao Shi Jiahao Deng Huayu li wenqi Zhao Shukai Ding Qingmei Su Bingshe Xu Materials Institute of Atomic and Molecular Science Shaanxi University of Science and TechnologyXi'an 710021ShanxiChina Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan 030024ShanxiChina Key Laboratory of Interface Science and Engineering in Advanced Materials Taiyuan University of TechnologyTaiyuan 030024ShanxiChina

Layer-type liNi0.9Mn0.1O2is promising to be the primary cathode material for lithium-ion batteries(liBs)due to its excellent electrochemical ***,the cathode with high nickel content suffers from severely detrimental structural transformation that causes rapid capacity ***,site-specific dual-doping with Fe and Mg ions is proposed to enhance the structural stability of *** Fe3+dopants are inserted into transition metal sites(3b)and can favorably provide additional redox potential to compensate for charge and enhance the reversibility of anionic *** Mg ions are doped into the li sites(3a)and serve as O_(2)^(-)-Mg^(2+)-O_(2)^(-)pillar to reinforce the electrostatic cohesion between the two adjacent transition-metal layers,which further suppress the cracking and the generation of harmful phase transitions,ultimately improving the *** theoretical calculations,including Bader charge and crystal orbital Hamilton populations(COHP)analyses,confirm that the doped Fe and Mg can form stable bonds with oxygen and the electrostatic repulsion of O_(2)^(-)-O_(2)^(-)can be effectively suppressed,which effectively mitigates oxygen anion loss at the high delithiation *** dual-site doping strategy offers new avenues for understanding and regulating the crystalline oxygen redox and demonstrates significant potential for designing high-performance cobalt-free nickel-rich cathodes.

关键词： Cobalt-free Layered oxide Cathode Dual dopants Density functional theory calculation

A novel cabazitaxel liposomes modified with ginsenoside Rk1 for cancer targeted therapy

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Acupuncture and Herbal Medicine 2024年第1期4卷 113-121页

作者： Dandan Huang Zhongjie Tang Xiao Pu Tianqi wang Feiyan Gao Chong li Medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqingChina Department of Pharmacy National University of SingaporeSingapore 117545Singapore

Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-lip).Methods:Physical and chemical properties of Rk1/CTX-lip were *** evaluated the biological functions of Rk1/CTXlip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-lip inhibition in ***,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/***,biocompatibility and in vivo safety of Rk1/CTX-lip were ***:We successfully prepared Rk1/CTX-lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical ***1/CTX-lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/***,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior ***:Rk1/CTX-lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.

关键词： Cabazitaxel Fungal infection Ginsenoside Rk1 liposome-drug delivery system Prostate cancer

Surface doping effect on the optoelectronic performance of 2D organic crystals based on cyano-substituted perylene diimides

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Chinese Chemical Letters 2024年第9期35卷 193-197页

作者： Jaeyong Ahn Zhenping li Zhiwei wang Ke Gao Huagui Zhuo Wanuk Choi Gang Chang Xiaobo Shang Joon Hak Oh School of Chemical and Biological Engineering Institute of Chemical ProcessesSeoul National UniversitySeoul 08826South Korea State Key Laboratory for Mechanical Behavior of Materials Shaanxi International Research Center for Soft MatterSchool of Materials Science and EngineeringXi’an Jiaotong UniversityXi’an 710049China Center for Ordered Nanoporous Materials Synthesis School of Environmental Science and EngineeringPohang University of Science and TechnologyGyeongbuk 37673South Korea Instrumental Analysis Center of Xi’an Jiaotong University Xi’an 710049China

Compared to organic thin films,organic single crystals offer significant potential in organic phototransistors(OPTs)due to their enhanced charge transport,large surface area,and defect-free ***,the development of n-type semiconductors has lagged behind p-type *** enhance semiconductor device performance,a doping process can be employed,which typically involves the introduction of charged impurities into the crystalline semiconducting *** aim is to reduce the Ohmic losses,increase carrier density,improve transport capabilities,and facilitate effective carrier injection,ultimately enhancing the electrical properties of the *** doping processes,however,often pose a risk of damaging the structure of single *** this study,we have synthesized novel cyanosubstituted chiral perylene diimides,which self-assemble into two-dimensional single crystals that can be used for n-type semiconductor *** have employed a surface doping strategy using diethylamine vapor without disrupting the crystal *** fabricated devices exhibit significantly higher charge transport properties after doping,achieving a maximum electron mobility of 0.14 cm^(2)V^(-1)s^(-1),representing an improvement of over ***,the optoelectronic performance of the doped devices has significantly improved,with the external quantum efficiency increased by over 9 times and the significantly improved response *** results suggest that our surface doping technology is a promising way for enhancing the performance of 2D organic single-crystal OPTs.

关键词： Doping effect Phototransistors Perylene diimides Organic crystals Cyano substitution

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

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Chinese Journal of Cancer Research 2024年第3期36卷 270-281页

作者： Guojie Feng Jiao li Nuo Yu Ziyu Zheng Xiongtao Yang Lei Deng Tao Zhang wenqing wang wenyang liu Jianyang wang Qinfu Feng Jima Lyu Zefen Xiao Zongmei Zhou Nan Bi Jianjun Qin Xin wang Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal ***,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this ***,there is a need for a more suitable radiotherapy combination regimen for this *** study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)***:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were *** were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive *** primary endpoint was the locoregional control(LRC)***:A total of 55 patients who met the study criteria were *** completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 *** median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]*** LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire *** overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,*** was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events ***:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

关键词： Esophageal carcinoma squamous cell carcinoma nutritional risk score nimotuzumab S-1 definitive chemoradiotherapy