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Effects of apical sodium-bile acid transporter inhibitor and obeticholic acid co-treatment in experimental non-alcoholic steatohepatitis

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Liver Research 2022年第4期6卷 276-283页

作者： David J.Matye Xuan Qin Mohammad Nazmul Hasan Lijie Gu yung dai clayton Feng Li Tiangang Li Harold Hamm Diabetes Center Department of PhysiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA Department of Pathology and Immunology Baylor College of MedicineHoustonTXUSA NMR and Drug Metabolism Core Baylor College of MedicineHoustonTXUSA

Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many ***,we have shown that combining a gut-restricted apical sodium-bile acid transporter(ASBT)inhibitor GSK2330672(GSK)with adeno-associated virus(AAV)-mediated liver fibroblast growth factor 15(FGF15)overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat,cholesterol,and fructose(HFCFr)diet-induced NASH mouse *** beneficial effects of the com-bined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid *** aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid(OCA),which induces endogenous FGF15 and inhibits hepatic bile acid synthesis,can achieve similar anti-NASH effect as the GSKþAAV-FGF15 co-treatment in HFCFr-diet-fed *** and methods:Male C57BL/6J mice were fed HFCFr diet to induce NASH and liver *** effect of GSK,OCA,and GSKþOCA treatments on NASH development was compared and contrasted among all ***:Findings from this study showed that the GSKþOCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment *** single treatment nor the GSKþOCA co-treatment reduce hepatic steatosis,but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar *** GSKþOCA co-treatment caused a higher degree of total bile acid pool reduction(~55%)than either GSK or OCA treatment ***,such bile acid pool reduction was insufficient to cause increased fecal lipid *** GSKþOCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression.

关键词： Bile acids Farnesoid X receptor(FXR) Fibroblast growth factor 15(FGF15) Apical sodium-bile acid transporter(ASBT) Non-alcoholic steatohepatitis(NASH) Liver fibrosis

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“If I Do not Go to Work, They Will Die!” Dual Roles of Older-Adult Personal Support Workers' Contributions During the COVID-19 Pandemic

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International Journal of Disaster Risk Science 2024年第2期15卷 226-238页

作者： Haorui Wu Mandy yung School of Social Work Faculty of HealthDalhousie UniversityHalifaxNS B3H 4R2Canada

When COVID-19 devastated older-adult organizations(long-term care homes and retirement homes), most public attention was directed toward the older-adult residents rather than their service providers. This was especially true in the case of personal support workers, some of whom are over the age of 55, putting them in two separate categories in the COVID-19 settings:(1) a vulnerable and marginalized group who are disproportionately impacted by COVID-19;and(2) essential healthcare workers. Since the current disaster-driven research, practice, and policy have primarily focused on generalized assumptions that older-adults are a vulnerable, passive, and dependent group rather than recognizing their diversity, expertise, assets, and experiences, this study aimed to identify their contributions from the perspective of older-adult personal support worker(OAPSW). This qualitative study conducted in-depth interviews, inviting 15 OAPSWs from the Greater Toronto Area, Canada. This study uncovered the OAPSWs' contribution at three levels: individual(enhancing physical health, mental health, and overall well-being), work(improving working environment and service and supporting co-workers), and family(protecting their nuclear and extended families). The outcomes inform the older-adult research, practice, policy, public discourse, and education by enhancing the appreciation of older-adults' diverse strengths and promoting their engagement and contributions in disaster settings.

关键词： Canada COVID-19 Individual-work-family triangulation Older-adult personal support workers

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Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 665-669页

作者： Wei-Yu Huang yung-Jen Chen Department of Ophthalmology Chi Mei Medical CenterTainan City 710TaiwanChina Department of Ophthalmology Chang Gung Memorial HospitalKaohsiung City 833TaiwanChina

AIM:To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses(IOLs).METHODS:This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June *** patients underwent comprehensive preoperative and postoperative ophthalmologic examination,and data were collected including age,sex,surgical indications,best-corrected visual acuity,refractive error,intraocular *** of intraoperative and postoperative surgical complications was ***:A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±*** acuity improved from a mean of 0.35(0.46±0.32 logMAR)preoperatively to 0.61(0.21±0.18 logMAR)at the 3-month follow-up(P=0.002).The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was-1.24±0.80 diopters(D)and-1.42±0.97 D,*** was no statistically significant difference between preoperative and postoperative astigmatism(P=0.156).The mean IOL-induced astigmatism was-0.23±0.53 *** mean spherical equivalent at the 3-month follow-up was-0.1±0.94 *** major complications were noted during the follow-up ***:Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

关键词： intraocular lens dislocation intraocular lens subluxation lens dislocation lens subluxation scleral fixation

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On the Specificity of Nanozymes: A Perspective

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Chinese Journal of Chemistry 2024年第13期42卷 1515-1522页

作者： Gen Wei Shuje Liu yung-Kang Peng Hui Wei Department of Biomedical Engineering College of Engineering and Applied SciencesNanjing National Laboratory of MicrostructuresJiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjingJiangsu 21023China Department of Chemistry.City University of Hong Kong Hong Kong 999077Hong Kong SARChina State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjingJiangsu 210023China NMPA Key Laboratory for Biomedical Optics HangzhouZhejiang 310018China

We have compiled eight promising strategies for enhancing the specificity and selectivity of nanozymes,as depicted in the comprehensive summary *** exhibit intricate and sophisticated structures,including substrate channels and active sites,which can inform the design of *** of these structural features and the application of facet engineering/doping techniques can significantly enhance the catalytic specificity of ***,the use of Molecularly Imprinted Polymers(MiPs)to coat nanozymes represents an effective approach to impart substrate ***,several straightforward stopgap strategies have been devised to improve nanozyme specificity for analytical applications,such as the integration of biorecognition elements and nanozyme sensor arrays through surface modification.

关键词： Nanozymes Enzymes Catalytic activity Specificity Perspective

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All-optical complex field imaging using diffractive processors

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Light(Science & Applications) 2024年第6期13卷 1122-1139页

作者： Jingxi Li Yuhang Li Tianyi Gan Che-yung Shen Mona Jarrahi Aydogan Ozcan Electrical and Computer Engineering Department University of CaliforniaLos AngelesCA90095USA Bioengineering Department University of CaliforniaLos AngelesCA90095USA California NanoSystems Institute(CNSI) University of CaliforniaLos AngelesCA90095USA

Complex field imaging,which captures both the amplitude and phase information of input optical fields or objects,can offer rich structural insights into samples,such as their absorption and refractive index ***,conventional image sensors are intensity-based and inherently lack the capability to directly measure the phase distribution of a *** limitation can be overcome using interferometric or holographic methods,often supplemented by iterative phase retrieval algorithms,leading to a considerable increase in hardware complexity and computational ***,we present a complex field imager design that enables snapshot imaging of both the amplitude and quantitative phase information of input fields using an intensity-based sensor array without any digital *** design utilizes successive deep learning-optimized diffractive surfaces that are structured to collectively modulate the input complex field,forming two independent imaging channels that perform amplitude-to-amplitude and phase-to-intensity transformations between the input and output planes within a compact optical design,axially spanning~100 *** intensity distributions of the output fields at these two channels on the sensor plane directly correspond to the amplitude and quantitative phase profiles of the input complex field,eliminating the need for any digital image reconstruction *** experimentally validated the efficacy of our complex field diffractive imager designs through 3D-printed prototypes operating at the terahertz spectrum,with the output amplitude and phase channel images closely aligning with our numerical *** envision that this complex field imager will have various applications in security,biomedical imaging,sensing and material science,among others.

关键词： field. utilize collective

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High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

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Journal of Magnesium and Alloys 2024年第1期12卷 295-315页

作者： Xuan He Ye Li Hongwei Miao Jiankun Xu Michael Tim-yun Ong Chenmin Wang Lizhen Zheng Jiali Wang Le Huang Haiyue Zu Zhi Yao Jie Mi Bingyang dai Xu Li Patrick Shu-hang yung Guangyin Yuan Ling Qin Musculoskeletal Research Laboratory of Department of Orthopaedics&Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongHong KongChina National Engineering Research Center of Light Alloy Net Forming School of Materials Science&EngineeringShanghai Jiao Tong UniversityShanghaiChina Department of Orthopaedics and Traumatology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Orthopaedic Department Peking University Third HospitalBeijingChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong KongChina

After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing *** good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during ***,tensile strength,degradation,and cytotoxicity of ZG21 wire are *** rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical *** SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying *** tests demonstrate the high formability of ZG21 wire as surgical ***-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing *** mechanical test shows higher ultimate load in the ZG21 *** SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)*** results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of *** vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate *** vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon *** conclusion,the ZG21 wire is feasible for tendon graft *** degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

关键词： Magnesium wire ACL reconstruction Magnesium alloy Biomaterials Endochondral ossification

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Regulation of PM_(2.5)on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol

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Journal of Environmental Sciences 2024年第4期138卷 288-300页

作者： Shanshan Chen Wenqi Chen Zhiping Li Jianwei Yue Ken Kin Lam yung Ruijin Li Institute of Environmental Science Shanxi UniversityTaiyuan 030006China Institute of Judicial Identification Techniques for Environmental Damage Shanxi University and Shanxi Unisdom Testing Technology Co.Ltd.Taiyuan 030006China Department of Biology Hong Kong Baptist UniversityHong KongChina Shanxi Yellow River Laboratory Taiyuan 030006China

Fine particulate matter(PM_(2.5))exposure is associated with cardiovascular disease(CVD)morbidity and *** are sensitive targets of PM_(2.5),and mitochondrial dysfunction is closely related to the occurrence of *** epigenetic mechanism of PM_(2.5)-triggered mitochondrial injury of cardiomyocytes is *** study focused on the mi R-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM_(2.5).Results illustrated that PM_(2.5)impaired mitochondrial function and caused dynamics homeostasis ***,PM_(2.5)up-regulated mi R-421 and down-regulated SIRT3 gene expression,along with decreasing p-FOXO3a(SIRT3 downstream target gene)and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene ***,mi R-421 inhibitor(mi R-421i)and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM_(2.5)exposure and mediated the expression of SOD2,OPA1 and Drp1,restoring the mitochondrial morphology and *** suggests that mi R-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM_(2.5)and that mi R-421i and resveratrol exert protective effects against PM_(2.5)-incurred cardiotoxicity.

关键词： Fine particulate matter Rat H9c2 cells Mitochondrial damage MiR-421 SIRT3 Resveratrol

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Highly Accurate Golden Section Search Algorithms and Fictitious Time Integration Method for Solving Nonlinear Eigenvalue Problems

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1317-1335页

作者： Chein-Shan Liu Jian-Hung Shen Chung-Lun Kuo yung-Wei Chen Center of Excellence for Ocean Engineering Taiwan Ocean UniversityKeelung202301TaiwanChina Department of Marine Engineering Taiwan Ocean UniversityKeelung202301TaiwanChina

This study sets up two new merit functions,which are minimized for the detection of real eigenvalue and complex eigenvalue to address nonlinear eigenvalue *** each eigen-parameter the vector variable is solved from a nonhomogeneous linear system obtained by reducing the number of eigen-equation one less,where one of the nonzero components of the eigenvector is normalized to the unit and moves the column containing that component to the right-hand side as a nonzero input vector.1D and 2D golden section search algorithms are employed to minimize the merit functions to locate real and complex ***,the real and complex eigenvectors can be computed very accurately.A simpler approach to the nonlinear eigenvalue problems is proposed,which implements a normalization condition for the uniqueness of the eigenvector into the eigenequation *** real eigenvalues can be computed by the fictitious time integration method(FTIM),which saves computational costs compared to the one-dimensional golden section search algorithm(1D GSSA).The simpler method is also combined with the Newton iterationmethod,which is convergent very *** the proposed methods are easily programmed to compute the eigenvalue and eigenvector with high accuracy and efficiency.

关键词： Nonlinear eigenvalue problem quadratic eigenvalue problem two new merit functions golden section search algorithm fictitious time integration method

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Sampling-efficient path planning and improved actor-critic-based obstacle avoidance for autonomous robots

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Science China(Information Sciences) 2024年第5期67卷 197-214页

作者： Yefeng YANG Tao HUANG Tianqi WANG Wenyu YANG Han CHEN Boyang LI Chih-yung WEN Department of Aeronautical and Aviation Engineering The Hong Kong Polytechnic University Center for Control Theory and Guidance Technology Harbin Institute of Technology School of Engineering The University of Newcastle Research Center for Unmanned Autonomous Systems The Hong Kong Polytechnic University

Autonomous robots have garnered extensive utilization in diverse fields. Among the critical concerns for autonomous systems, path planning holds paramount importance. Notwithstanding considerable efforts in its development over the years, path planning for autonomous systems continues to grapple with challenges related to low planning efficiency and inadequate obstacle avoidance response in a timely *** study proposes a novel and systematic solution to the path planning problem within intricate office buildings. The solution consists of a global planner and a local planner. To handle the global planning aspect, an adaptive clustering-based dynamic programming rapidly exploring random tree(ACDP-RRT) algorithm is proposed. ACDP-RRT effectively identifies obstacles on the map by leveraging geometric *** obstacles are then represented as a collection of sequentially arranged convex polygons, optimizing the sampling region and significantly enhancing sampling efficiency. For local planning, a network decoupling actor-critic(ND-AC) algorithm is employed. The proposed ND-AC simplifies the local planner design process by integrating planning and control loops into a neural network(NN) trained via an end-to-end model-free deep reinforcement learning(DRL) framework. Moreover, the adoption of network decoupling(ND) techniques leads to an improved obstacle avoidance success rate when compared to conventional actor-critic(AC)-based methods. Extensive simulations and experiments are conducted to demonstrate the effectiveness and robustness of the proposed approach.

关键词： rapidly exploring random tree (RRT) adaptive clustering network decoupling actor critic (AC) path planning

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Highly conductive and tough double-network hydrogels for smart electronics

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SmartMat 2024年第2期5卷 54-66页

作者： Dong Zhang Yijing Tang Xiong Gong yung Chang Jie Zheng Department of Chemical Biomolecularand Corrosion EngineeringThe University of AkronAkronOhioUSA School of Polymer Science and Polymer Engineering The University of AkronAkronOhioUSA R&D Center for Membrane Technology and Department of Chemical Engineering Chung Yuan Christian UniversityTaiwanChina

Development and understanding of highly mechanically robust and electronically conducting hydrogels are extremely important for ever-increasing energy-based *** mixing/blending of conductive additives with hydrophilic polymer network prevents both high mechanical strength and electronic conductivity to be presented in polymer ***,we proposed a double-network(DN)engineering strategy to fabricate PVA/PPy DN hydrogels,consisting of a conductive PPy-PA network via in-situ ultrafast gelation and a tough PVA network via a subsequent freezing/thawing *** resultant PVA/PPy hydrogels exhibited superior mechanical and electrochemical properties,including electrical conductivity of~6.8 S/m,mechanical strength of~0.39 MPa,and elastic moduli of~0.1 *** further transformation of PVA/PPy hydrogels into supercapacitors,they demonstrated a high capacitance of~280.7 F/g and a cycle life of 2000 galvanostatic charge/discharge cycles with over 94.3%capacity retention at the current density of 2 mA/cm2 and even subzero temperatures of−20℃.Such enhanced mechanical performance and electronic conductivity of hydrogels are mainly stemmed from a synergistic combination of continuous electrically conductive PPy-PA network and the two interpenetrating DN *** in-situ gelation strategy is applicable to the integration of ionic-/electrical-conductive materials into DN hydrogels for smart-soft electronics,beyond the most commonly used PEDOT:PSS-based hydrogels.

关键词： conducting polymers double-network hydrogels smart electronics supercapacitors

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