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Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong Chen wei Yang Ligong Chen Jianping ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic Disease Research Center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Research Center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter *** transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and *** actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

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Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai ye Xin-Ni Li wei-Guang Li Department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

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A Video Captioning Method by Semantic Topic-Guided Generation

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Computers, Materials & Continua 2024年第1期78卷 1071-1093页

作者： Ou ye Xinli wei zhenhua Yu Yan Fu Ying Yang College of Computer Science and Technology Xi’an University of Science and TechnologyXi’an710054China

In the video captioning methods based on an encoder-decoder,limited visual features are extracted by an encoder,and a natural sentence of the video content is generated using a ***,this kind ofmethod is dependent on a single video input source and few visual labels,and there is a problem with semantic alignment between video contents and generated natural sentences,which are not suitable for accurately comprehending and describing the video *** address this issue,this paper proposes a video captioning method by semantic topic-guided ***,a 3D convolutional neural network is utilized to extract the spatiotemporal features of videos during the ***,the semantic topics of video data are extracted using the visual labels retrieved from similar video *** the decoding,a decoder is constructed by combining a novel Enhance-TopK sampling algorithm with a Generative Pre-trained Transformer-2 deep neural network,which decreases the influence of“deviation”in the semantic mapping process between videos and texts by jointly decoding a baseline and semantic topics of video *** this process,the designed Enhance-TopK sampling algorithm can alleviate a long-tail problem by dynamically adjusting the probability distribution of the predicted ***,the experiments are conducted on two publicly used Microsoft Research Video Description andMicrosoft Research-Video to Text *** experimental results demonstrate that the proposed method outperforms several state-of-art ***,the performance indicators Bilingual Evaluation Understudy,Metric for Evaluation of Translation with Explicit Ordering,Recall Oriented Understudy for Gisting Evaluation-longest common subsequence,and Consensus-based Image Description Evaluation of the proposed method are improved by 1.2%,0.1%,0.3%,and 2.4% on the Microsoft Research Video Description dataset,and 0.1%,1.0%,0.1%,and 2.8% on the Microsoft Research-Video to Text dataset

关键词： Video captioning encoder-decoder semantic topic jointly decoding Enhance-TopK sampling

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In-situ measurement via the flow-through method and numerical simulations for radon exhalation during measurements of the radon exhalation rate

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Nuclear Science and Techniques 2024年第7期35卷 192-207页

作者： Ming Xia Yong-Jun ye Shan-wei Shang Ting Yu Dai-Jia Chen School of Resources Environment and Safety Engineering University of South ChinaHengyang421001China Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy University of South ChinaHengyang421001China

Small-scale measurements of the radon exhalation rate using the flow-through and closed-loop methods were conducted on the surface of a uranium tailing pond to better understand the differences between the two *** abnormal radon exhalation behavior was observed,leading to computational fluid dynamics(CFD)-based simulations in which dynamic radon migration in a porous medium and accumulation chamber was *** on the in-situ experimental and numerical simulation results,variations in the radon exhalation rate subject to permeability,flow rate,and insertion depth were quantified and *** in-situ radon exhalation rates measured using the flow-through method were higher than those measured using the closed-loop method,which could be explained by the negative pressure difference between the inside and outside of the chamber during the *** consistency of the variations in the radon exhalation rate between the experiments and simulations suggests the reliability of CFD-based techniques in obtaining the dynamic evolution of transient radon exhalation rates for diffusion and convection at the porous medium-air *** synergistic effects of the three factors(insertion depth,flow rate,and permeability)on the negative pressure difference and measured exhalation rate were quantified,and multivariate regression models were established,with positive correlations in most cases;the exhalation rate decreased with increasing insertion depth at a permeability of 1×10^(−11) m^(2).CFD-based simulations can provide theoretical guidance for improving the flow-through method and thus achieve accurate measurements.

关键词： Radon exhalation Flow-through Numerical simulation Accumulation chamber Multivariate regression

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Carbon-based nanomaterials cause toxicity by oxidative stress to the liver and brain in Sprague-Dawley rats

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Nuclear Science and Techniques 2024年第6期35卷 54-64页

作者： Ying-Ying Xu Chan Jin Meng Wu Jian-ye Zhou Hui-Ling wei Department of Gastroenterology China-Japan Friendship HospitalBeijing 100029China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China Institute of Particle and Nuclear Physics College of PhysicsHenan Normal UniversityXinxiang 453007China

Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug ***,the human and ecological risks associated with carbon-based nanomaterials have received increasing ***,the biological safety of carbon based nanomaterials has not been systematically *** this study,we used different types of carbon materials,namely,graphene oxide(GO),single-walled carbon nanotubes(SWCNTs),and multiwalled carbon nanotubes(MWCNTs),as models to observe their distribution and oxidative damage in *** results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these ***-μ-XRF analysis revealed that SWCNTs and MWCNTs might be present in the *** shows that the three types of carbon-based nanomaterials could cross the gas-blood barrier and eventually reach the liver *** addition,SWCNTs and MWCNTs could cross the blood-brain barrier and accumulate in the cerebral *** increase in ROS and MDA levels and the decrease in GSH,SOD,and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the *** suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS *** addition,iron(Fe)contaminants in these nanomaterials were a definite source of free ***,these nanomaterials did not cause obvious damage to the rat brain *** deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe *** information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.

关键词： Carbon-based nanomaterials Oxidative stress Trace element distribution TEM SR-μ-XRF

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Shoulder hemiarthroplasty for the treatment of complex proximal humeral fractures

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Chinese Journal of Traumatology 2009年第1期12卷 -页

作者： YANG Shu-hua WANG Jing XU wei-hua LI Jin LIU Guo-hui YANG Can ye Shu-nan ye zhe-wei LIU Yong Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Objective: To investigate the indication, perioperative announcements, selection of prosthesis and clinical results of shoulder hemiarthroplasty for the treatment of complex proximal humeral ***: A total of 55 patients who suffered from com-plex proximal humeral fractures were treated by shoulder hemiarthroplasty. The mean age was 55.6 years and mean follow-up period was 25.1 months. The scoring system modi-fication for hemiarthroplasty (SSMH) had been adopted for evaluation at the latest ***: The pain was obviously relieved in all patients. Fifty patients were painless and 5 patients had slight pain. The mean range of motion was 100°(90°-110°) in abduction, 95°(80°-100°) in forward flexion, 35°(30°-40°) in extemal rotation and internal rotation was confined at L2 level (L1-L3). The mean SSMH score was 27.9 (24-29). Fifty patients (90.1%) were satisfied with the clinical ***: Shoulder hemiarthroplasty is an effective method to treat complex proximal humeral fractures. The proper selection of patients and prosthesis, good operation skill and enough functional exercise are the key points of successful treatment.

关键词： Shoulder Arthroplasty Humeral fractures Prosthesis implantation

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Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military Medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He ye-Hua Li Si-Cong Zhao zhe-Min Shi Li-Na zheng Tao Han wei Hong Department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

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Investigation on cavitating turbulent flow for the twisted NACA66 hydrofoil using a PANS model with helicity modification

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Journal of Hydrodynamics 2024年第2期36卷 219-231页

作者： Chen Geng Zhao-hui Qian Ke-xin zheng wei-xiang ye Xian-wu Luo State Key Laboratory of Hydroscience cand Engineering Deparment of Energy and Power EngineeringTsinghua UniversityBeijing 100084China Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084China

In the present paper,the unsteady cavitating turbulent flow over the twisted NACA66 hydrofoil is investigated based on an modified shear stress transfer k-ωpartially averaged Navier-Stokes(MSST PANS)model,i.e.,new MSST PANS(NMSST PANS)model,where the production term of kinetic energy in the turbulence model is modified with *** with the experimental data,cavitation evolution and its characteristic frequency are satisfactorily predicted by the proposed NMSST PANS *** is revealed that the interaction among the main flow,the reentrant jets,and sheet cavitation causes the formation of the primary shedding cavity near the mid-span and the secondary shedding cavity at each side of the twisted hydrofoil,and further induces the remarkable pressure gradient around shedding *** with the development of the primary and the secondary shedding cavities,the great pressure gradient associated with large cavity volume variation promotes the vortical flow generation and the spatial deformation of vortex structure during cavitation evolution,and results in the primary and the secondary U-type ***,dynamic mode decomposition(DMD)analysis is utilized to confirm the interaction among the main flow,the main reentrant jet and two side reentrant jets,and *** results indicate that the proposed NMSST PANS model is suitable to simulate the complicated cavitating turbulent flow for various engineering applications.

关键词： Cavitating turbulent flow partially averaged Navier-Stokes(PANS)model hydrofoil numerical simulation

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Investigation of the block toppling evolution of a layered model slope by centrifuge test and discrete element modeling

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第1期16卷 112-122页

作者： Leilei Jin Hongkai Dong Fei ye Yufeng wei Jianfeng Liu Changkui Wang State Key Laboratory of Hydraulic and Mountain River Engineering College of Water Resource and HydropowerSichuan UniversityChengdu610065China State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Chengdu University of TechnologyChengdu610059China

Primary toppling usually occurs in layered rock slopes with large anti-dip *** this paper,the block toppling evolution was explored using a large-scale centrifuge *** block column in the layered model slope was made of cement *** artificial cracks perpendicular to the block column were *** gages,displacement gages,and high-speed camera measurements were employed to monitor the deformation and failure processes of the model *** centrifuge test results show that the block toppling evolution can be divided into seven stages,*** compression,formation of major tensile crack,reverse bending of the block column,closure of major tensile crack,strong bending of the block column,formation of failure zone,and complete *** toppling is characterized by sudden large deformation and occurs in *** wedge-shaped cracks in the model incline towards the *** observations show that block toppling is mainly caused by bending failure rather than by shear *** tensile strength also plays a key factor in the evolution of block *** simulation results from discrete element method(DEM)is in line with the testing *** stress exists at the backside of rock column during toppling *** concentration results in the fragmented rock column and its degree is the most significant at the slope toe.

关键词： Block toppling Centrifuge Anti-dip slope Failure mechanism Discrete element method

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Advances in Polymeric Carbon Nitride Photocatalysts for Enhanced CO_(2)Reduction

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China Petroleum Processing & Petrochemical Technology 2024年第2期26卷 1-12页

作者： Liu Bing Sun Shangcong Song ye Peng Bo Lin wei SINOPEC Research Institute of Petroleum Processing Co. Ltd.Beijing100083China

Photocatalysis has emerged as a promising alternative for converting and utilizing CO_(2).Polymeric carbon nitride(PCN),typically synthesized through the one-step thermal polycondensation of nitrogen-rich precursors,has shown considerable promise due to its adjustable band structure and inherent *** the past five years,significant literature in this field has identified five primary methods for modifying PCN:morphology modulation,element doping,defect induction,co-catalyst loading,and heterojunction construction.A detailed discussion on how each modification method influences light absorption,charge separation,and surface reaction efficiencies in photocatalysis is *** on these findings,several future directions for the development of PCN-based materials are proposed,such as designing tailored PCN structures for specific photocatalytic reactions and using theoretical calculations to verify and correct results from current characterization *** the challenges associated with the large-scale synthesis of PCN materials with controllable structures and satisfactory performance,this work offers valuable insights for advancing photocatalytic PCN-based systems for large-scale solar fuel production.

关键词： carbon nitride photocatalysis CO_(2)reduction modification

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