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NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Zoological Research 2024年第4期45卷 857-874页

作者： Na Zhao Xiu Chen Qiu-gu Chen Xue-Ting Liu Fan Geng meng-meng Zhu Fu-Ling Yan Zhi-Jun Zhang Qing-guo Ren Department of Neurology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Neurology Affiliated Zhongda HospitalSoutheast UniversityNanjingJiangsu 210009China

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive ***,the underlying mechanisms remain *** the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic *** findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the *** with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived ***,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic ***,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau ***,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive ***,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

关键词： Chronic sleep deprivation Tau pathology NLRP3 inflammasome Autophagy GSK-3β Microbiota-gut-brain axis

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Effect of Mn addition on microstructure and mechanical properties of GX40CrNiSi25-12 austenitic heat resistant steel

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China Foundry 2024年第3期21卷 205-212页

作者： guan-yu Jiang meng-wu Wu xiao-guang Yang Hui Wang Yu-yuan Zhu Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China Hubei Longzhong Laboratory Xiangyang 441000HubeiChina Wescast Industries(China)Co. Ltd.Wuhan 430100China

Three types of steels were designed on the basis of GX40CrNiSi25-12 austenitic heat resistant steel by adding different Mn contents(2wt.%,6wt.%,and 12wt.%).Thermodynamic calculation,microstructure characterization and mechanical property tests were conducted to investigate the effect of Mn addition on the microstructure and mechanical properties of the austenitic heat resistant *** show that the matrix structure in all the three types of steels at room temperature is completely *** NbC and M_(23)C_(6)precipitate at grain boundaries of austenite *** the increase of Mn content,the number of carbides increases and their distribution becomes more *** the Mn content increases from 1.99%to 12.06%,the ultimate tensile strength,yield strength and elongation increase by 14.6%,8.0%and 46.3%,*** improvement of the mechanical properties of austenitic steels can be explained by utilizing classic theories of alloy strengthening,including solid solution strengthening,precipitation strengthening,and grain *** increase in alloy strength can be attributed to solid solution strengthening and precipitation strengthening caused by the addition of *** improvement of the plasticity of austenitic steels can be explained from two aspects:grain refinement and homogenization of precipitated phases.

关键词： austenitic heat resistant steel manganese microstructure mechanical properties

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Roles of transforming growth factor-βsignaling in liver disease

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World Journal of Hepatology 2024年第7期16卷 973-979页

作者： xiao-Ling Wang meng Yang Ying Wang Clinical Laboratory Shanxi Academy of Traditional Chinese MedicineTaiyuan 030012Shanxi ProvinceChina

In this editorial we expand the discussion on the article by Zhang et al published in the recent issue of the World Journal of *** focus on the diagnostic and therapeutic targets identified on the basis of the current understanding of the molecular mechanisms of liver *** growth factor-β(TGF-β)belongs to a structurally related cytokine super *** family members display different time-and tissue-specific expression patterns associated with autoimmunity,inflammation,fibrosis,and tumorigenesis;and,they participate in the pathogenesis of many ***-βand its related signaling pathways have been shown to participate in the progression of liver diseases,such as injury,inflammation,fibrosis,cirrhosis,and *** often studied TGF-β/Smad signaling pathway has been shown to promote or inhibit liver fibrosis under different ***,the early immature TGF-βmolecule functions as a tumor suppressor,inducing apoptosis;but,its interaction with the mitogenic molecule epidermal growth factor alters this effect,activating anti-apoptotic signals that promote liver cancer ***,TGF-βsignaling displays contradictory effects in different liver disease ***,the use of TGF-βand related signaling pathway molecules for diagnosis and treatment of liver diseases remains a challenge and needs further *** this editorial,we aim to review the evidence for the use of TGF-βsignaling pathway molecules as diagnostic or therapeutic targets for different liver disease stages.

关键词： Transforming growth factor-βsignaling Liver disease Molecular mechanism Targets Diagnosis

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The reservoir characteristics and their controlling factors of the sublacustrine fan in the Paleogene Dongying Formation, Bohai Sea,China

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Journal of Palaeogeography 2024年第1期13卷 127-148页

作者： xiao-Jun Pang guan-Min Wang meng Zhao Qing-Bin Wang Xue-Fang Zhang School of Geosciences China University of Petroleum(East China)QingdaoShandong 266580China Tianjin Branch of China National Offshore Oil Corporation Limited Tianjin 300459China

Sublacustrine fan is an important element in continental lacustrine basins and is significant for reservoir exploration. Oil and gas resources have been found in the sublacustrine fan sandstone reservoirs of the Paleogene Dongying Formation in the Bohai Sea. In this study, the characteristics of the sublacustrine fan reservoirs and the controlling factors are studied using information from logging, cores, physical properties,casting thin sections, X-ray diffraction of clay minerals, vitrinite reflectance, rock pyrolysis, manometry data,and 3D seismic data. The sublacustrine fans of the Dongying Formation in the LD10, QHD34, and BZ21 structures show high-quality reservoirs with porosity >15 % and permeability >5 m D. The main controlling factors of the high-quality reservoirs are attributed to the favorable sedimentary facies type and negligible compaction,and cementation, substantial dissolution of K-feldspar, overpressure, and the development of faults and fractures. A high-quality sublacustrine fan reservoir model has been established to explain how these factors affected the physical properties. The favorable targets for oil and gas exploration in the Dongying Formation of Bohai Sea include undercompacted sandy debris flow reservoirs showing the dissolution of K-feldspar, and the reservoirs which are connected to the source rocks by faults. This study provides insights to establish the relationship between sedimentology, diagenesis and reservoir quality. The results of this study are significant for the exploration and development of the sublacustrine fan sandstone reservoirs in the Bohai Sea and analogous sandstone reservoirs elsewhere.

关键词： Sublacustrine fan High-quality reservoir Dissolution Overpressure Fault Bohai Sea

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang gu Shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

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The influences of perforating phase and bedding planes on the fracture deflection in laminated shale

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Petroleum Science 2024年第2期21卷 1221-1230页

作者： Ming-Zhe gu Mao Sheng xiao-Ying Zhuang Xin-Yi Li Gen-Sheng Li National Key Laboratory of Petroleum Resources and Engineering China University of PetroleumBeijing102249China College of Petroleum Engineering China University of PetroleumBeijing102249China College of Civil Engineering Tongji UniversityShanghai200092China

The perforating phase leads to complex and diverse hydraulic fracture propagation behaviors in laminated shale formations. In this paper, a 2D high-speed imaging scheme which can capture the interaction between perforating phase and natural shale bedding planes was proposed. The phase field method was used to simulate the same conditions as in the experiment for verification and hydraulic fracture propagation mechanism under the competition of perforating phase and bedding planes was *** results indicate that the bedding planes appear to be no influence on fracture propagation while the perforating phase is perpendicular to the bedding planes, and the fracture propagates along the perforating phase without deflection. When the perforating phase algins with the bedding planes, the fracture initiation pressure reserves the lowest value, and no deflection occurs during fracture propagation. When the perforating phase is the angle 45°, 60°and 75°of bedding planes, the bedding planes begin to play a key role on the fracture deflection. The maximum deflection degree is reached at the perforating phase of75°. Numerical simulation provides evidence that the existence of shale bedding planes is not exactly equivalent to anisotropy for fracture propagation and the difference of mechanical properties between different shale layers is the fundamental reason for fracture deflection. The findings help to understand the intrinsic characteristics of shale and provide a theoretical basis for the optimization design of field perforation parameters.

关键词： Shale Propagation Perforating Bedding Structure

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Reduction behavior of iron ore powder by high-volatile coal in thermogravimetric-gas chromatographic and kinetic analysis

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Journal of Iron and Steel Research(International) 2024年第1期31卷 92-107页

作者： Rui-meng Shi Qi-yuan Mi Bin Li xiao Shi Chong Zou Jing guo Han-jie guo School of Metallurgical Engineering Xi’an University of Architecture and TechnologyXi’an710055ShaanxiChina China International Engineering Consulting Corporation Beijing100048China School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing100083China

The reduction behavior of iron ore powder by high-volatile coal was investigated,and its kinetic mechanism was *** effect of volatiles in coal on the reduction reaction of iron ore was compared by utilizing a Xinjiang lignite with a high volatile content and its pyrolysis carbon produced by high-temperature pyrolysis to remove volatiles,serving as a *** mass loss and gas composition of the samples during the reduction process were detected using thermo-gravimetric analysis and gas chromatography,and the morphological changes of iron ore powder were observed through scanning electron *** kinetic parameters of the iron oxide reduction reaction were calculated by the Flynn-Ozawa-Wall method,and the kinetic mechanism of volatile participation in the iron oxide reduction reaction was determined through the Coats-Redfern *** results indicate that the coupling effect between the high-volatile coal pyrolysis and reduction reactions occurs during the second stage of the entire coupling process,which corresponds to the late stage of coal pyrolysis with a substantial release of H_(2)and *** volatiles in coal actively participated in the reduction reaction,reducing the initiation temperature of the reaction by around 200℃.The reduction of iron oxides by high-volatile coal was jointly promoted by the"hydrogen cycle"and"carbon cycle",resulting in a higher reduction extent and metallization rate at the end of the *** high-volatile coal was used as the reductant,the average activation energy for the entire process was 76.5 kJ/mol,a significant decrease compared to the employment of pyrolysis carbon without volatiles as the reductant(1167 kJ/mol).

关键词： Direct reduction High-volatile coal Volatile Kinetics Reduction mechanism

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Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors

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Nano Research 2024年第2期17卷 836-847页

作者： Shuping Li Xin Li Jiaqi meng Weier Bao Shuang Wang Peng Ye xiao-Dong Gao Wei Wei Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of BiotechnologyJiangnan UniversityWuxi 214122China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China

Bacterial outer membrane vesicles(OMVs)are potent immunostimulants of regulating the tumor microenvironment(TME)for immunotherapy,and can be used to deliver ***,the severe systemic inflammatory response triggered by OMVs upon intravenous(i.v.)injection has limited their ***,we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin(SA-DOX,AD)onto the surface of OMVs using a matrix metalloproteinase(MMP)-cleavable peptide linker(cL).This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through ***,the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after ***,facilitated by the SA decoration on the OMVs ***,the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME,leading to the release of both OMVs and *** process provided OMV-induced immunotherapy and DOX-induced chemotherapy,resulting in synergistic tumor *** conclusion,our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.

关键词： outer membrane vesicles doxorubicin tumor microenvironment immunotherapy chemotherapy

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Construction of a Cu@hollow TS-1 nanoreactor based on a hierarchical full-spectrum solar light utilization strategy for photothermal synergistic artificial photosynthesis

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Carbon Energy 2024年第2期6卷 25-36页

作者： Sixian Zhu Qiao Zhao Hongxia guo Li Liu xiao Wang Xiwei Qi Xianguang meng Wenquan Cui Hebei Key Laboratory for Environment Photocatalytic and Electrocatalytic Materials College of Chemical EngineeringNorth China University of Science and TechnologyTangshanChina School of Materials Science and Engineering National Institute for Advanced MaterialsTKL of Metal and Molecule-Based Material ChemistryNankai UniversityTianjinChina Hebei Iron and Steel Laboratory TangshanChina

The artificial photosynthesis technology has been recognized as a promising solution for CO_(2) *** catalysis has been proposed as a novel strategy to promote the efficiency of artificial photosynthesis by coupling both photochemistry and ***,strategies for maximizing the use of solar spectra with different frequencies in photothermal catalysis are urgently ***,a hierarchical full-spectrum solar light utilization strategy is *** on this strategy,a Cu@hollow titanium silicalite-1 zeolite(TS-1)nanoreactor with spatially separated photo/thermal catalytic sites is designed to realize high-efficiency photothermal catalytic artificial *** space-time yield of alcohol products over the optimal catalyst reached 64.4μmol g−1 h−1,with the selectivity of CH3CH2OH of 69.5%.This rationally designed hierarchical utilization strategy for solar light can be summarized as follows:(1)high-energy ultraviolet light is utilized to drive the initial and difficult CO_(2) activation step on the TS-1 shell;(2)visible light can induce the localized surface plasmon resonance effect on plasmonic Cu to generate hot electrons for H2O dissociation and subsequent reaction steps;and(3)low-energy near-infrared light is converted into heat by the simulated greenhouse effect by cavities to accelerate the carrier *** work provides some scientific and experimental bases for research on novel,highly efficient photothermal catalysts for artificial photosynthesis.

关键词： artificial photosynthesis full spectrum nanoreactors photothermal catalysis

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Method for rapid warning and activity concentration estimates in online waterγ-spectrometry systems

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Nuclear Science and Techniques 2024年第3期35卷 1-12页

作者： meng Wang Yi gu Mao-Lin Xiong Liang-Quan Ge Qing-Xian Zhang guo-Qiang Zeng Heng Lu Sheng-Liang guo College of Nuclear Technology and Automation Engineering Chengdu University of TechnologyChengdu 610059China Applied Nuclear Technology in Geosciences Key Laboratory of Sichuan Province (Chengdu University of Technology)Chengdu 610059China Chengdu New Ray Technology Co.Ltd Chengdu 610052China

Onlineγ-spectrometry systems for inland waters,most of which extract samples in situ and in real time,are able to produce reliable activity concentration measurements for waterborne radionuclides only when they are distributed relatively uniformly and enter into a steady-state diffusion regime in the measurement *** protect residents’health and ensure the safety of the living environment,better timeliness is required for this measurement *** address this issue,this study established a mathematical model of the online waterγ-spectrometry system so that rapid warning and activity estimates can be obtained for water under non-steady-state(NSS)*** addition,the detection efficiency of the detector for radionuclides during the NSS diffusion process was determined by applying the computational fluid dynamics technique in conjunction with Monte Carlo *** this basis,a method was developed that allowed the online waterγ-spectrometry system to provide rapid warning and activity concentration estimates for radionuclides in *** analysis of the NSS-mode measurements of^(40)K radioactive solutions with different activity concentrations determined the optimum warning threshold and measurement time for producing accurate activity concentration estimates for *** experimental results show that the proposed NSS measurement method is able to give warning and yield accurate activity concentration estimates for radionuclides 55.42 and 69.42 min after the entry of a 10 Bq/L^(40)K radioactive solution into the measurement chamber,*** times are much shorter than the 90 min required by the conventional measurement ***,the NSS measurement method allows the measurement system to give rapid(within approximately 15 min)warning when the activity concentrations of some radionuclides reach their respective limits stipulated in the guidelines for Drinking-water Quality of the WHO,suggesting that this method con

关键词： Water radioactivity monitoring Dynamic detection efficiency Rapid warning Activity estimation

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