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PLAU plays a functional role in driving lung squamous cell carcinoma metastasis

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Genes & Diseases 2024年第2期11卷 554-557页

作者： Pengbo Ning Fuyu Du Xiaocheng Gong Jingtong Yuan Caixia Ding Xilian Zhao Wei Li School of Life Science and Technology Xidian UniversityXi'anShaanxi 710071China Engineering research Center of Molecular & Neuroimaging Ministry of EducationXi'anShaanxi 710071China Department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Pathology Shaanxi Provincial Tumor HospitalXi'an Jiaotong UniversityXi'anShaanxi 710061China

The high mortality of patients with lung squamous cell carcinoma(LUSC)results from metastasis rather than primary tumors,1 whereas the molecular pathogenesis of cancer metastasis remains poorly *** encodes urokinase-type plasminogen activator(uPA)which is closely related to tumor diagnosis,treatment target,and prognosis of patients.2.3 We previously predicted that PLAU is a key gene negatively associated with overall survival by integrated multidimensional analyses of The Cancer Genome Atlas(TCGA)datasets from 504 samples of LUSC tumor tissues and 46 samples of adjacent non-tumorous lung tissues.4 However,whether the role of PLAU contributes to the metastasis of LUC remains ***,we analyzed the association between uPA levels and LUSC and found that uPA levels were associated with pathological variations in LUSC patients.

关键词： metastasis lung squamous

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

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Cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： Ming Bai Yao Lu Chunmei Shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba Department of GI Medical Oncology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerTianjin 300060China Fujian Medical University Union hospital Fuzhou 350001China Fujian Provincial Cancer hospital Fuzhou 350014China Cancer Center The First Hospital of Jilin UniversityChangchun 130021China Department of Medical Oncology Gastroenterology and Urology Hunan Cancer HospitalAffiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Oncology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing)Peking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering research Center of Protein and Antibody Sinocelltech Ltd.Bejing 100176China Department of Cancer Center Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100010China

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical *** with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and *** primary endpoints were the objective response rate(ORR)and *** secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,*** ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,*** treatment-related adverse events(TRAEs)were ***,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination ***:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety *** head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration ***04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1

A Robust N-Terminal Pro-Brain Natriuretic Peptide Assay for Clinical Diagnosis of heart Failure in Elderly Patients

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Journal of Analysis and Testing 2024年第1期8卷 74-82页

作者： Xue Gong Jiangling Wu Jiajia Zhang Zhongwei Jiang Yi Wang Pu Zhang Engineering research Center for Biotechnology of Active Substances(Ministry of education) Chongqing Key Laboratory of Green Synthesis and ApplicationsCollege of ChemistryChongqing Normal UniversityChongqing 401331China Chongqing research Center for Pharmaceutical Engineering College of PharmacyChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory University Town Hospital of Chongqing Medical UniversityChongqing 401331China

heart failure(HF)is a clinical hallmark of cardiovascular syndrome leading to substantial morbidity,repeated hospitalization,and enormous healthcare *** elderly populations continue to increase,biomarker-guided diagnosis and treatment for age-related cardiac decline have become *** evidence demonstrates that N-terminal proBNP(NT-proBNP)can provide a unique window into the diagnosis and risk stratification with ***,a simple yet robust aptasensor is developed for on-site recognizing the NT-proBNP by its targeting aptamer,thus achieving the accurate diagnosis of *** aptasensing system is prepared by absorbing the fluorophore-labeled aptamer strand onto the graphene oxide(GO),leading to efficient quenching without possible off-site signal *** aptamer strand can specifically identify target NT-proBNP molecules via a versatile conformational transformation,resulting in the desorption of the aptamer-NTproBNP complexes from GO and re-generation fluorescence signal,thus allowing sensitive detection of NT-proBNP in 37 clinical blood *** advantage of the high specificity of aptamer-guaranteed recognitions of NT-proBNP,this aptasensor system readily achieves better diagnostic performance for HF than commercially adopted chemiluminescence immunoassay(Siemens,CLIA)in hospitals in terms of accuracy(89.2%vs 83.8%),specificity(89.5%vs 84.2%),and positive predictive value(88.9%vs 83.3%).This work provides a stable option for the diagnosis and treatment of elderly HF-related diseases inclinics.

关键词： NT-proBNP Graphene oxide Aptamer heart failure Clinical diagnosis

Nanocomposite: Keggin-type Co_(4)-polyoxometalate@cobaltporphyrin linked graphdiyne for hydrogen evolution in seawater

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Nano research 2024年第3期17卷 1281-1287页

作者： Jiejie Ping Danyang He Fei Wang Nan Wang Yi-cheng Fu Zihao Xing Zhiyu Jia Guo-Yu Yang Key Laboratory of Cluster Science Ministry of EducationSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of education Facluty of Chmeistry Northeast Normal UniversityChangchun 130024China Peking University Third hospital Beijing 100190China

Polyoxometalate-based nanocomposites with electrocatalytic activity have been applied in hydrogen evolution reactions(HER).Seawater as the main water resource on the earth should be developed as the water electrolysis to prepare high-purity *** this paper,we used two synthesis strategies to prepare the nanocomposite Co_(4)-POM@Co-PGDY(Co_(4)-POM:the Kegging-type microcrystals of K_(10)[Co_(4)(PW_(9)O_(3)4)2]and Co-PGDY:cobalt-porphyrin linked graphdiyne)with excellent activity for ***-PGDY as the porous material is applied not only as the protection of microcrystals towards the metal ion in seawater but also as the co-electrocatalyst of Co_(4)-***_(4)-POM@Co-PGDY exhibits excellent HER performance in seawater electrolytes with low overpotential and high stability at high ***,we have observed a key H_(3)O+intermediate emergence on the surface of nanocomposite during hydrogen evolution process in seawater by Raman synchrotron radiation-based Fourier transform infrared(SR-FTIR).The results in this paper provide an effective strategy for preparing polyoxometalate-based electrocatalysts with high-performance toward hydrogen evolution reaction.

关键词： polyoxometalate graphdiyne seawater hydrogen evolution reaction

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

Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & Diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Gynecology and Obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and Gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological *** have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the ***-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid *** are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor ***,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian *** found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor *** by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in *** of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test:insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy

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Neural Regeneration research 2024年第5期19卷 1098-1104页

作者： Siyun Chen Mengchai Mao Guangyue Zhu Yufeng Chen Yuqi Qiu Bin Ye Dongsheng Xu The Second Rehabilitation hospital of Shanghai ShanghaiChina College of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina School of Statistics East China Normal UniversityShanghaiChina The Third Rehabilitation hospital of Shanghai ShanghaiChina Tongji University ShanghaiChina Shuguang hospital Affiliated to Shanghai University of Traditional Chinese Medicine ShanghaiChina

After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional *** arm training has been proposed as a promising intervention to address these ***,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted *** address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and ***-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand *** found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly ***,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test ***,the observed neural response patterns varied depending on the specific *** the unaffected hand task,the differences were primarily observed in the ipsilesional *** contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,*** significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual *** study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural resp

关键词： bilateral arm training bimanual coordination cortical activity fine motor dexterity functional near-infrared spectroscopy(fNIRS) high-functioning Purdue Pegboard Test stroke

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

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Neuroscience Bulletin 2024年第5期40卷 621-634页

作者： Xiuxiu Liu Ying Zhang Yanming Zhao Qian Zhang Feng Han Medical Basic research Innovation Center for Cardiovascular and Cerebrovascular Diseases Ministry of EducationNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China Institute of Brain Science The Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou210019China

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous *** pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous *** current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting *** this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic *** early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic *** this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

关键词： Epileptogenesis Neurovascular unit Molecular mechanisms Drug targets

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2885-2900页

作者： Porkizhi Arjunan Durga Kathirvelu Gokulnath Mahalingam Ashish Kumar Goel Uday George Zacharaiah Alok Srivastava Srujan Marepally Center for Stem Cell research(A Unit of inStem Bengaluru)Christian Medical College CampusBagayamVellore 632002Tamil NaduIndia Manipal academy for higher education Mangalore 576104KarnatakaIndia Department of Hematology Christian Medical College&HospitalVellore 632004Tamil NaduIndia Department of Hepatology Christian Medical College&HospitalVellore 632004Tamil NaduIndia

Inherited genetic disorders of the liver pose a significant public health *** transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive *** overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable *** viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their *** a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and ***,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

关键词： Lipid nanoparticle Liver disorders Gene therapy Gene editing Nucleic acid delivery pDNA mRNA siRNA ASO Clinical trials