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Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

International Journal of Ophthalmology(English edition) 2024年第5期17卷 806-814页

作者： si-Rui Zhou Yu-Sheng Zhu Wen-Ting Yuan Xiao-yan Pan Tong Wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell ***:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in *** viability was detected by a Cell Counting Kit-8 *** proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,*** expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot *** MET and phosphorylated MET proteins were also determined by immunofluorescence ***:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT ***11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT ***11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 ***,SU11274 also blocked HGF-induced phosphorylation of MET and AKT ***:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor ***-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

关键词： hepatocyte growth factor mesenchymal epithelial transition factor SU11274 retinal pigment epithelial cells

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Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces

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Chinese Medical Sciences Journal 2024年第2期39卷 131-139页

作者： Xue-Qin Wang Hong-Qiang Sun Jia-Yue si Zi-yan Lin Xiao-Mei Zhai Lin Lu Peking University sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Chinese Academy of Medical Sciences Research Unit(No.2018RU006)Beijing 100191China Department of Psychology University of CaliforniaDavis 95616USA Department of Psychology University of TorontoToronto M5S 1A1Canada School of Population Medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Academy for Advanced Interdisciplinary Studies Peking-Tsinghua Centre for Life Sciences and Peking University-International Development Group/McGovern Institute for Brain ResearchPeking UniversityBeijing 100871China

Brain-computer interface(BCI)technology is rapidly advancing in medical research and *** an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental ***,BCI also raises several challenges and ethical concerns in clinical *** this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical *** the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in *** ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.

关键词： brain-computer interface clinical research bioethics ethical governance ethical review

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Universal paradigm of ternary metacomposites with tunable epsilon-negative and epsilon-near-zero response for perfect electromagnetic shielding

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Rare Metals 2024年第2期43卷 796-809页

作者： Yun-Peng Qu Yun-Lei Zhou yang Luo Yao Liu Jun-Fei Ding yan-Li Chen Xiu Gong Jing-Liang yang Qiong Peng Xiao-si Qi College of Physics Guizhou UniversityGuiyang550025China Hangzhou Institute of Technology Xidian UniversityHangzhou311231China Department of Materials ETH Zurich8093ZurichSwitzerland Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials(Ministry of Education) Shandong UniversityJinan250061China

CaCu_(3)Ti_(4)O_(12)(CCTO)ceramic nanocomposites incorporating graphene–carbon black(GRCB)fillers were fabricated by spark plasma sintering *** percolative effects of conductive GRCB fillers on dielectric response of GRCB/CCTO ternary metacomposites were systematically *** weakly real permittivity(ε′)-negative response(ε′~−1×10^(2))was achieved which originated from weakly low-frequency plasmonic state of free carriers within constructed GRCB *** enhancing three-dimensional GRCB network,the plasma frequency of metacomposites increased while the damping factor ***,theε′-negative values of metacomposites were tuned from−10^(2) to−10^(4) orders of magnitude andε′-near-zero(ENZ)frequencies from~142 to~340 MHz which substantially benefited from the moderate carrier concentration of GRCB dual *** Drude model and equivalent circuit models were adopted to demonstrate dielectric and electrical *** obtained metacomposites show strong EM shielding effect along with enhanced plasmonic oscillation and even better achieving perfect EM shielding effect in ENZ *** work achieves the tunableε′-negative andε′-near-zero response and more importantly clarifies its regulation mechanism in ceramic-based ternary metacomposites,which opens up the possibility of designing high-performance EM shielding materials based on metacomposites.

关键词： Metacomposites Ceramic matrix composites Negative permittivity Epsilon-near-zero Electromagnetic shielding

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： si-yang Liu Song Dong Xue-Ning yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong yan Li-Xu yan Qiang Nie Hai-yan Tu Bin-Chao Wang Jin-Ji yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu si-yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Measurement of the high energyγ-rays from heavy ion reactions usingČerenkov detector

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Nuclear Science and Techniques 2024年第2期35卷 123-130页

作者： Da-Wei si yan Zhou Sheng Xiao Zhi Qin Dong Guo Yu-Hao Qin Yi-Jie Wang Bo-Yuan Zhang Bai-Ting Tian Zhi-Gang Xiao Department of Physics Tsinghua UniversityBeijing 100084China

The energetic bremsstrahlung photons up to 100 MeV produced in heavy ion collisions can be used as a sensitive probe for short-range correlation in atomic nuclei. The energy of the γ-rays can be measured by collecting the Čerenkov light in the medium induced by the fast electrons generated in the Compton scattering or electromagnetic shower of the incident γray. Two types of detectors based on pure water and lead glass as sensitive materials were designed for this purpose. The γresponse and optical photon propagation in the detectors were simulated based on electromagnetic and optical processes in Geant4. The inherent energy resolutions of 0.022(4) + 0.51(2)∕E^(1/2)_(γ) for water and 0.0026(3) + 0.446(3)∕E^(1/2)_(γ) for lead glass were obtained. The geometry sizes of the lead glass and water were optimized to 30 cm × 30 cm × 30 cm and 60 cm × 60 cm ×120 cm, respectively, to detect high-energy γ-rays at 160 MeV. The Hough transform method was applied to reconstruct the direction of the incident γ-rays, providing the ability to experimentally distinguish the high-energy γ-rays produced in the reactions on the target from random background cosmic-ray muons.

关键词： Bremsstrahlungγ-rays Čerenkov Geant4 Energy resolution Direction reconstruction Hough transform

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The role of botanical triterpenoids and steroids in bile acid metabolism,transport,and signaling:Pharmacological and toxicological implications

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Acta Pharmaceutica sinica B 2024年第8期14卷 3385-3415页

作者： Zichen Luo Wei Zhou Tong Xie Weichen Xu Chen Shi Zihan Xiao Yu si yan Ma Qingling Ren Liuqing Di Jinjun Shan Medical Metabolomics Center Institute of PediatricsJiangsu Key Laboratory of Children’s Health and Chinese MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu CM Clinical Medicine Innovation Center for Obstetrics Gynecologyand ReproductionAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210001China National Institute of Biological Sciences Beijing 102206China Jiangsu Engineering Research Center for Efficient Delivery System of TCM School of PharmacyNanjing University of Chinese MedicineNanjing 210023China

Bile acids(BAs)are synthesized by the host liver from cholesterol and are delivered to the intestine,where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various *** serve to emulsify dietary lipids and act as signaling molecules,regulating the host’s metabolism and immune homeostasis through specific ***,disruptions in BA metabolism,transport,and signaling are closely associated with cholestasis,metabolic disorders,autoimmune diseases,and *** triterpenoids and steroids share structural similarities with BAs,and they have been found to modulate BA metabolism,transport,and signaling,potentially exerting pharmacological ortoxicological ***,we have updated the research progress on BA,with a particular emphasis on new-found microbial ***,the latest advancements in targeting BA metabolism and signaling for disease treatment are ***,the roles of botanical triterpenoids in BA metabolism,transport,and signaling are examined,analyzing their potential pharmacological,toxicological,or drug interaction effects through these ***,a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

关键词： Bile acid Triterpenoid Phytosterol Saponin Gut microbes Cholestasis Metabolic disorders Rheumatoid arthritis

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Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

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World Journal of Gastroenterology 2024年第13期30卷 1911-1925页

作者： Fei-Lin Ge yan yang Lan-Lan si Yuan-Hua Li Meng-Zhen Cao Jun Wang Zhao-Fang Bai Zhi-Gang Ren Xiao-He Xiao yan Liu Department of Chinese Medicine State Key Laboratory of Antiviral DrugsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina The Fifth Medical Center of Chinese PLA General Hospital Beijing 100039China College of Traditional Chinese Medicine Chongqing Medical UniversityChongqing 400010China Beijing Key Laboratory of Emerging Infectious Diseases Peking University Ditan Teaching HospitalBeijing 100015China Department of Infectious Diseases State Key Laboratory of Antiviral Drugsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)*** studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains *** To investigate the potential mechanism of action of LWWL against *** In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell *** in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV *** and metabolomics were used to investigate the underlying mechanisms of action of *** In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,*** inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,*** of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,Psignificant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups

关键词： Hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis

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SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong yang Yongsheng Wang Hong Jian Zibin Liang Sheng Hu Min Peng yan Yu yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses

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Procyanidin Aand its digestive products inhibit acrylamide-induced IPEC-J2 cell damage: apoptosis and cell cycle arrest

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Food Science and Human Wellness 2024年

作者： Fangfang yan si Qin Chengming Wang Wolfram Weckwerth Qun Lu Rui Liu Lab of Food Function and Nutrigenomics， College of Food Science and Technology， Hunan Agricultural University College of Food Science and Technology， Huazhong Agricultural University Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University)， Ministry of Education Molecular Systems Biology， Department of Functional and Evolutionary Ecology， University of Vienna

Our previous study has demonstrated that procyanidin A1(A1) and its simulated digestive product (D-A1) can prevent acrylamide （ACR）-induced cytotoxicity in small intestine cells. However， the potential mechanism remains poorly understood. In this study， ACR treatment was found to increase the levels of 8-hydroxy-deoxyguanine （8-OHdG） and phosphorated histone H2AX (γH2AX)， two DNA damage markers， thereby resulting in cell cycle arrest in the G2/M phase; whereas both A1and D-A1could prevent the phosphorylation of ataxia telangiectasia mutated （ATM） and checkpoint kinase 2 （Chk2）， and then regulate the expression of G2/M phase-related proteins， finally maintaining normal cell cycle progression. Moreover， A1and D-A1could increase the B cell lymphoma 2 （Bcl-2）/Bcl2-associated X （Bax） ratio and decrease the expression of cleaved caspase-3 and cleaved caspase-9 proteins to alleviate ACR-induced cell apoptosis， which might be related to the inhibition of the mitogen-activated protein kinase （MAPK） pathway. More importantly， A1showed no remarkable variation in inhibitory effect before and after digestion， indicating that it can endure gastrointestinal digestion and may be a promising phytochemical to alleviate ACR-induced intestinal cell damage.

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Light-induced stepped thermal relaxation in a Hofmann-type metal-organic framework

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Science China Chemistry 2024年第6期67卷 1983-1989页

作者： Wen Cui Wei-Wei Wu Ze-Yu Ruan yan-Cong Chen Guang-Jun Zeng Guan-Xi Chen si-Guo Wu Zhao-Ping Ni Ming-Liang Tong Key Laboratory of Bioinorganic and Synthetic Chemistry of Ministry of Education School of ChemistryInstitute of Green Chemistry and Molecular EngineeringGuangdong Basic Research Center of Excellence for Functional Molecular EngineeringSun Yat-sen UniversityGuangzhou510275China

Spin-crossover(SCO)materials with light-induced multistability have potential applications in multi-addressable opto-magnetic memory devices and multiple ***,we reported a three-dimensional Hofmann-type metal-organic framework(MOF)[Fe(bpy){Pt(CN)_(4)}]·coumarin(1·coumarin,bpy=4,4′-bipyridine),which exhibits an incomplete and hysteretic SCO *** importantly,the light-induced stepped thermal relaxation(LISTR)with obvious magnetic plateau for a hidden intermediate spin state is firstly *** hidden spin state is also observed for the first time in the thermal relaxation after light-assisted spin state annealing(LASSA).Meanwhile,an extremely rare bi-directional light-induced excited spin-state trapping(LIESST)with the highest reverse-LIESST temperature is ***,five spin states can be captured in 1·coumarin and the tristability can be modulated below 102 K through the excitation-relaxation ***,the light-and temperatureinduced multistability provides a new strategy for developing multistable materials.

关键词： light magnetic multistability iron metal-organic framework spin-crossover

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