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Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1845-1863页

作者： Jie Zhou Binyang Gao Huan Zhang Rui yang Jianbo Huang Xin Li Yi zhong yan wang Xiaoxia Zhu yan Luo feng yan Ultrasound Department of West China Hospital Sichuan UniversityChengdu 610041China Laboratory of Ultrasound Imaging of West China Hospital Sichuan UniversityChengdu 610041China West China Washington Mitochondria and Metabolism Research Center West China HospitalSichuan UniversityChengdu 610041China Research Core Facilities of West China Hospital Sichuan UniversityChengdu 610041China

Lipid-coated perfluorocarbon nanodroplets(lp-NDs)hold great promise in bio-medicine as vehicles for drug delivery,molecular imaging and vaccine ***,their clinical utility is restricted by limited targeted accumulation,attributed to the innate immune system(IIS),which acts as the initial defense mechanism in *** study aimed to optimize lp-ND formulations to mini-mize non-specific clearance by the ***(Gs),the principal components of Panax ginseng,possessing complement inhibition ability,structural similarity to cholesterol,and comparable fat solubi-lity to phospholipids,were used as promising candidate IIS *** different types of ginsenoside-based Ip-NDs(Gs Ip-NDs)were created,and their efficacy in reducing IS recognition was *** Gs p-NDs were observed to inhibit the adsorption of C3 in the protein corona(PC)and the generation of *** Gs to Ip-NDs reduced complement adsorption and phagocytosis,resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain *** results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants,potentially reducing non-specific clear-ance by the IS and improving lifespan.

关键词： Lipid-coated perfluorocarbon nanodroplets Protein corona Complement C3 Phagocytosis Ginsenosidelipid-coated perfluorocarbon nanodroplets Innate immune system Complement system Mononuclear phagocytic system

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Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1613-1625页

作者： Xiao-Min Zhang Ting yang ying-ying Xu Bao-zhong Li Wei Shen Wen-qing Hu Cai-Wen yan Liang Zong Department of Central Laboratory Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastrointestinal Surgery Yizheng People’s HospitalThe Affiliated Hospital of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina Department of General Surgery Anyang Tumor HospitalAnyang 455000Henan ProvinceChina Department of General Surgery Wuxi People’s Hospital Affiliated to Nanjing Medical UniversityWuxi 214023Jiangsu ProvinceChina Department of Gastrointestinal Surgery Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastroenterology Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric ***,it is unclear whether this combination is superior to chemotherapy *** To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal *** We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric *** employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion *** meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were *** performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy ***

关键词： Programmed cell death protein-1 inhibitor Chemotherapy Oesophageal squamous cell carcinoma Gastric/gastroesophageal junction adenocarcinoma Overall survival Progression-free survival Objective response rate Adverse event

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Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3362-3384页

作者： Yu Fan Ruibing feng Xinya Zhang Zhen-Liang wang feng Xiong Shuihua Zhang Zhang-feng zhong Hua Yu qing-Wen Zhang Zhang Zhang Yitao wang Guodong Li Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of Education(MoE)of People’s Republic of ChinaCollege of PharmacyJinan UniversityGuangzhou 510632China Zhuhai UM Science and Technology Research Institute Zhuhai 519031China Department of Pharmacy Guangzhou Red Cross HospitalFaculty of Medical ScienceJinan UniversityGuangzhou 510632China Geriatric Medicine First People’s Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453100China Shenzhen Innovation Center for Small Molecule Drug Discovery Co. Ltd.Shenzhen 518000China

Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge *** to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource *** review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical *** discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to *** also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market *** review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

关键词： Drug screening Phage display DNA-encoded chemical libraries Peptide-encoded chemical libraries Clinical drugs

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Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

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World Journal of Gastroenterology 2024年第10期30卷 1346-1357页

作者： Jing-feng Chen Zhuo-qing Wu Hao-Shuang Liu Su yan You-Xiang wang Miao Xing Xiao-Qin Song Su-ying Ding Health Management Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Institute of Systems Engineering Dalian University of TechnologyDalian 116024Liaoning ProvinceChina College of Public Health Zhengzhou UniversityZhengzhou 450001Henan ProvinceChina School of Basic Medicine and Forensic Medicine Henan University of Science and TechnologyLuoyang 471003Henan ProvinceChina

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD *** A cohort of 3553 participants followed for four consecutive health examinations over 4 years was *** incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were *** proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset *** A total of 83.13%of participants with MAFLD had normal ALT *** incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT *** with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,*** Most participants with MAFLD had normal ALT ***-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Cumulative effect Cox proportional hazards regression Cohort study

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High-efficiency crystalline white organic lightemitting diodes

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Light(Science & Applications) 2024年第4期13卷 747-759页

作者： Yijun Liu feng Zhu Yue wang Donghang yan State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China. School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China. State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun 130012China

Crystalline white organic light-emitting diodes(C-WOLEDs)are promising candidates for lighting and display *** is urgently necessary,however,to develop energy-saving and high-efficiency C-WOLEDs that have stable and powerful emission to meet commercial ***,we report a crystalline host matrix(CHM)with embedded nanoaggregates(NA)structure for developing high-performance C-WOLEDs by employing a thermally activated delayed fluorescence(TADF)material and orange phosphorescent dopants(Phos.-D).The CHM-TADFNA-D WOLED exhibit a remarkable EQE of 12.8%,which is the highest performance WOLEDs based on crystalline *** device has a quick formation of excitons and a well-designed energy transfer process,and possesses a fast ramping of luminance and current *** to recently reported high-performance WOLEDs based on amorphous material route,the C-WOLED achieves a low series-resistance Joule-heat loss ratio and an enhanced photon output,demonstrating its significant potential in developing the next-generation WOLEDs.

关键词： diodes dopant crystalline

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Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2113-2122页

作者： Jun-feng wang Xiao-Xia yang Jian Zhang yan Zheng Fu-qing Zhang Xiao-feng Shi Yu-Liang wang Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Neurology Tianjin First Center HospitalTianjin 300192China Prosthodontics Studio Tianjin Stomatological HospitalTianjin 300041China Department of Clinical Laboratory Medicine Tianjin Institute of UrologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Emergency Tianjin First Central HospitalTianjin 300192China

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of *** mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain *** supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent *** Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and ***,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release *** was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+*** The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg ***,ADSC-based cell therapy could be a beneficial approach for p

关键词： Colorectal cancer COVID-19 Adipose-derived mesenchymal stem cells T helper cell Immunomodulation

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Thermally modulated photoelectronic synaptic behavior in HfS_(2)/VO_(2) heterostructure

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Rare Metals 2024年第8期43卷 3798-3809页

作者： Le wang Lin wang Xiao-Yun Ye Xiong-Hu Xu Li-yan Shang Ya-Wei Li Jin-zhong Zhang Liang-qing Zhu Zhi-Gao Hu Technical Center for Multifunctional Magneto-Optical Spectroscopy(Shanghai) Engineering Research Center of Nanophotonics&Advanced Instrument(Ministry of Education)Department of PhysicsSchool of Physics and Electronic ScienceEast China Normal UniversityShanghai 200241China Collaborative Innovation Center of Extreme Optics Shanxi UniversityTaiyuan 030006China

Neuromorphic computing is known for its efficient computational speed,low latency,and reduced power consumption,which is considered a pivotal technology to overcome the von Neumann *** synapses are an indispensable component of neuromorphic computational artificial neural *** guarantee effective and precise processing of optical signals,it must have a high responsivity,detectivity,and the ability to adapt to various ***,a synaptic transistor based on the HfS_(2)/VO_(2) heterojunction with a responsivity of8.6×10^(3) A·W^(-1)and a detectivity of 1.26×10^(14)Jones at405 nm laser was ***,the typical synaptic behavior was successfully simulated,including postsynaptic currents(PSCs),the transition from shortterm plasticity(STP)to long-term plasticity(LTP).When VO_(2) converts from the semiconductor state to the metal state,the HfS_(2)/VO_(2) heterojunction transforms into a Schottky heterojunction from a TypeⅡheterojunction with ***'s important,the heterojunction still exhibits excellent responsivity and detectivity,as well as stability of synaptic *** addition,the classical Pavlovian conditioning experiment is simulated under different laser intensity to study the brain's associative learning *** results demonstrate that the HfS_(2)/VO_(2) heterojunction synapse exhibits significant responsivity and detectivity and is adaptable to high-temperature environments,showing great potential for neuromorphic computational applic ations.

关键词： HfS_(2) VO_(2) Phase transition Photoelectric synapse Heterojunction

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Root cause of corrosion failure of tin coating on wire clamp in marine atmosphere

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Journal of Iron and Steel Research International 2024年第4期31卷 998-1014页

作者： Zhen zhong wang-yan Ly Teng-yuan Liu Yi Xie yang yang Zhen-zhu wang Deng-ke Li Xiao-bo Li Tang-qing Wu School of Materials Science and Engineering Xiangtan UniversityXiangtan 411105HunanChina Electric Power Research Institute of Guangdong Power Grid Co. Ltd.Guangzhou 510080GuangdongChina Shenyang National L aboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016LiaoningChina School of Materials Science and Engineering.University of Science and Technology of China Shenyang 110016LiaoningChina Electric Power Research Institute State Grid Hunan Electric Power CompanyChangsha 410007HunanChina School of Mechanical Engineering and Mechanics Xiangtan UniversityXiangtan 411105HunanChina School of Information Science and Engineering Changsha Normal UniversityChangsha 410199HunanChina

The failure cause of a tinned copper wire clamp in marine atmosphere was studied systematically by X-ray photoelectron spectroscopy,scanning electron microscopy with energy dispersive spectroscopy and electrochemical *** main components of the green rust on the surface of the damaged wire clamp are SnO_(2),CuO,Cu_(2)Cl(OH)_(3) and CuCO(OH)_(2).Much of green rust distributes at the platform edge along the axial direction on the crimp connection,and severe corrosion and corrosion pits occur at the platform edge zone along the axial *** enriching Cl-at the marine atmosphere and the existing O_(2) in air collectively enhance the corrosion process of the tin coating and the copper *** element model results show that the residual stress and strain of the tin coating are the largest at the platform edge along the axial direction on the crimp connection,and the corresponding electrode potential of the tin coating at this zone drops *** above results indicate that the residual strain increases the driving force of the corrosion electrochemical reactions and accelerates the corrosion rate and the pit corrosion of the tin coating at this zone.

关键词： Tin coating Marine atmosphere Residual strain-Chloride ion Corrosion failure

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Cut-off value of glycated hemoglobin A1c for detecting diabetic retinopathy in the Chinese population

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World Journal of Diabetes 2024年第7期15卷 1531-1536页

作者： yan Wen qing wang Department of Endocrinology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina

BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and ***,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean populations in Jilin,China,remains *** To determine the best cut-off of HbA1c for diagnosing DR among the *** This cross-sectional study included 1933 participants from the yanbian area of Jilin Province,*** investigators employed a questionnaire-based survey,physical examination,laboratory tests,and fundus photography for the *** best cut-off value for HbA1c was established via the receiver operating characteristic *** factors associated with HbA1c-associated risk factors were determined via linear *** The analysis included 887 eligible Chinese Han and Korean participants,591 of whom were assigned randomly to the training set and 296 to the validation *** prevalence of DR was 3.27% in the total ***1c of 6.2% was the best cut-off value in the training set,while it was 5.9% in the validation *** both Chinese Han and Korean populations,an HbA1c level of 6.2% was the best cut-off *** optimal cut-off values of fasting blood glucose(FBG)≥7 mmol/L and<7 mmol/L were 8.1% and 6.2% respectively in Han populations,while those in Korean populations were 6.9%and 5.3%,***,body mass index,and FBG were determined as the risk factors impacting HbA1c *** HbA1c may serve as a useful diagnostic indicator for *** HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.

关键词： Diabetic retinopathy Glycated hemoglobin A1c Cut-off value Age Body mass index Fasting blood glucose

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Model Parameters Identification and Backstepping Control of Lower Limb Exoskeleton Based on Enhanced Whale Algorithm

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 100-114页

作者： yan Shi Jiange Kou Zhenlei Chen Yixuan wang qing Guo School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China School of Aeronautics and Astronautics University of Electronic Science and Technology of ChinaChengdu 611731China

Exoskeletons generally require accurate dynamic models to design the model-based controller conveniently under the human-robot interaction ***,due to unknown model parameters such as the mass,moment of inertia and mechanical size,the dynamic model of exoskeletons is difficult to ***,an enhanced whale optimization algorithm(EWOA)is proposed to identify the exoskeleton model ***,the periodic excitation trajectories are designed by finite Fourier series to input the desired position demand of exoskeletons with mechanical physical *** a backstepping controller based on the identified model is adopted to improve the human-robot wearable comfortable performance under cooperative ***,the proposed Model parameters identification and control are verified by a two-DOF exoskeletons *** knee joint motion achieves a steady-state response after 0.5 ***,the position error of hip joint response is less than 0.03 rad after 0.9 *** addition,the steady-state human-robot interaction torque of the two joints is constrained within 15 N·*** research proposes a whale optimization algorithm to optimize the excitation trajectory and identify model ***,an enhanced mutation strategy is adopted to avoid whale evolution’s unsatisfactory local optimal value.

关键词： Parameter identification Enhanced whale optimization algorithm(EWOA) Backstepping Human-robot interaction Lower limb exoskeleton

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