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Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease

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Medical Review 2024年第2期4卷 158-168页

作者： Zara Siu wa Chui Yaqian Xue Aimin Xu State Key Laboratory of Pharmaceutical Biotechnology The University of Hong KongHong Kong SARChina Department of Medicine The University of Hong KongHong Kong SARChina School of Biomedical Sciences The University of Hong KongHong Kong SARChina State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong999077Hong Kong SARChina Department of Medicine The University of Hong Kong999077Hong Kong SARChina Department of Pharmacology and Pharmacy The University of Hong Kong999077Hong Kong SARChina

Metabolic dysfunction-associated fatty liver disease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of *** its significant burden,there is no approved pharmacotherapy specifically tailored for this *** potential drug candidates for MAFLD have encountered setbacks in clinical trials,due to safety concerns or/and insufficient therapeutic ***,several investigational drugs that mimic the actions of endogenous metabolic hormones,including thyroid hormone receptorβ(THRβ)agonists,fibroblast growth factor 21(FgF21)analogues,and glucagon-like peptide-1 receptor agonists(gLP-1RAs),showed promising therapeutic efficacy and excellent safety *** them,resmetirom,a liver-targeted THRβ-selective agonist,has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis(MASH),the advanced form of MAFLD,and liver fibrosis in phase-3 clinical *** hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic ***more,these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects,suggesting their combined therapies may yield synergistic therapeutic *** in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies,enabling precision management of MAFLD and its associated comorbidities.

关键词： metabolic hormones metabolic dysfunctionassociated steatohepatitis(MASH) liver fibrosis biopharmaceutical development clinical trials

The earliest evidence for a microblade adaptation in the remote,high altitude regions of the Tibetan Plateau

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Science China Earth Sciences 2024年第5期67卷 1561-1573页

作者： Yingshuai JIN Xiaoling ZHANg Shejiang wa.g Junyi gE Wei HE wa DA Yunyao TAN Ziyi YANg Christopher MORgAN Xing gAO Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of SciencesBeijing 100044China University of the Chinese Academy of Sciences Beijing 100049China Cultural Relics Conservation Institute of the Xizang Autonomous Region Lhasa 850000China Nagqu Culture and Tourism Bureau Nagqu 852000China University of Nevada Reno 89557USA

Microblade assemblages are among the most common prehistoric archaeological materials found on the Tibetan Plateau(TP)and are thought to indicate large scale migration to and settlement of the *** microblade sites,however,have been systematically excavated,especially in the remotest,highest-elevation regions of the *** timing of the large-scale arrival,spread,and permanent settlement of people on the TP therefore remains *** this paper,we report on a recently excavated site,Locality 3 of the Nwya Devu Site(ND3),located at 4600 meters above sea level(masl),near the shore of Ngoin Lake,on the interior *** analyses reveal a fairly typical microblade technological orientation and two types of microblade cores:wedge-shaped and semi-conical,which are similar to those found throughout North *** Optically Stimulated Luminescence(OSL)dating and AMS^(14)C dating,the age of ND3 ranges from 11 to 10 *** date range indicates ND3 is the oldest microblade site yet recorded in the remote,high-elevation regions of the TP and thus provides important information about when and how hunter-gatherers using microblades began exploiting the higher altitudes of the *** together,studies at ND3 and throughout the TP suggest that a microblade adaptation is associated with the first prolonged human occupation of the plateau and that microblades played a significant role in mediating the risks and facilitating the mobility necessary to permanently inhabit the TP.

关键词： The interior of Tibetan Plateau Nwya Devu locality 3 Microblade Early Holocene High altitude adaption

Strengthening and control of second-phase particle precipitation in ferritic/austenitic/martensitic heat-resistant alloys:a review

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Journal of Iron and Steel Research International 2024年第1期31卷 3-23页

作者： Xue-cheng Peng Han-jie guo Xin-fang Zhang Yi-wa Luo Ye Sun Jing guo Rong-guang Yang Xiao-dan Zheng School of Metallurgical and Ecological Engineering University of Science and Technology Beijing(USTB)Beijing100083China Beijing Key Laboratory of Special Melting and Preparation of High-End Metal Materials University of Science and Technology Beijing(USTB)Beijing100083China Beijing Shougang gitane New MATERIALS Co. Ltd.Beijing102206China

Heat-resistant alloys with excellent mechanical properties are widely used in various fields,and further improvement in their properties is essential to meet the requirements in new-generation advanced supercritical boilers,nuclear reactors,superheaters,and other new materials *** effectively enhance the comprehensive performance of heat-resistant alloys,second-phase particle strengthening has been widely studied,and in the face of different service envi-ronments of advanced heat-resistant steels,the selection of suitable second-phase particles is essential to maximize the performance of these *** this end,three major types of reinforcing phases in heat-resistant alloys such as carbides,rare earth oxides,and intermetallic compounds are summarized.A comparative analysis of the precipitation behavior of the reinforcing phases with different types as well as the risks and means of controlling their use in service,is *** parameters for the application of various types of second-phase particles in heat-resistant alloys are provided to support the design and preparation of new ultrahigh-performance heat-resistant alloys.

关键词： Heat-resistant alloy Second-phase particle Carbide Rare earth oxide Intermetallic compound Strengthening

Deuterium distribution and behavior of blisters in pre-damaged and undamaged tungsten

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Tungsten 2024年第3期6卷 647-656页

作者： Cong Li Xiao-wa wa.g Ran-Ran Su Xuan-Xin Hu Shu-guang Wei Han-Jun Tu Li-Qun Shi Hong-Liang Zhang Key Laboratory of Nuclear Physics and Ion-Beam Application Institute of Modern Physics Fudan University School of Mechanical Engineering Shanghai Jiao Tong University Department of Materials Science and Engineering University of Wisconsin

Tungsten(W),as a plasma-facing material,is subjected to high fluence plasma,resulting in both radiation damage and deuterium(D) *** study explores the blistering behavior and D supersaturated layers in both pre-damaged and undamaged W *** achieve a uniform damage profile similar to neutron irradiation,carbon(C) ions with multiple energies and angles were *** samples were further irradiated with low-energy D ions under two fluences at temperatures from ～380 to 640 *** various experimental techniques,we found that pre-damaged W samples can effectively suppress the formation of blistering and lower the threshold temperature at which the surface remains free of *** also observed the prominent D supersaturated peaks within the depth of 20 nm in both pre-damaged and undamaged ***,a close correlation between blistering and the D supersaturation was *** results suggest that neutron irradiation in the fusion reactors could increase the critical D concentration for blistering,while a greater depth of damage facilitated the inward diffusion of D,thereby reducing the D concentration gradient and alleviating surface blistering.

关键词： Tungsten Deuterium Supersaturated layer Blister Ion irradiation Pre-damage

Supramolecular Manipulation of Intracellular Acidic Vesicles to Improve Cellular Self-Repair and Self-Defense

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CCS Chemistry 2024年第6期6卷 1487-1498页

作者： Ziyi wa.g Chen Sun Yu Dong Yuan-Fu Ding Chen Zhao Ian wa Ho Jiahong Lu Ruibing wa.g State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 999078China

Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and ***,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and ***,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEg)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEg-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ***,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic *** a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.

关键词： supramolecular chemistry organelle regulation intracellular acidic vesicles lysosomes selfdefense self-repair

Challenges and opportunities in the production of magnesium parts by directed energy deposition processes

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Journal of Magnesium and Alloys 2024年第5期12卷 1663-1686页

作者： gürel Cam Ali günen Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Mechanical Engineering31200 Iskenderun-HatayTurkey Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Metallurgy and Materials Engineering31200 Iskenderun-HatayTurkey

Mg-alloys have gained considerable attention in recent years for their outstanding properties such as lightweight,high specific strength,and corrosion resistance,making them attractive for applications in medical,aerospace,automotive,and other transport ***,their widespread application is hindered by their low formability at room temperature due to limited slip *** Mg-alloys have low mechanical properties due to the presence of casting defects such as porosity and anisotropy in addition to the high *** casting methods benefit from established process optimization techniques for these problems,additive manufacturing methods are increasingly replacing casting methods in Mg alloys as they provide more precise control over the microstructure and allow specific grain orientations,potentially enabling easier optimization of anisotropy properties in certain *** metal additive manufacturing(MAM)technology also results in some manufacturing defects such as inhomogeneous microstructural evolution and porosity and additively manufactured Mg alloy parts exhibit lower properties than the wrought parts,they in general exhibit superior properties than the cast ***,MAM is a promising technique to produce Mg alloy *** energy deposition processes,particularly wire arc directed energy deposition(wa-DED),have emerged as an advantageous additive manufacturing(AM)technique for metallic materials including magnesium alloys,offering advantages such as high deposition rates,improved material efficiency,and reduced production costs compared to subtractive ***,the inherent challenges associated with magnesium,such as its high reactivity and susceptibility to oxidation,pose unique hurdles in the application of this *** review paper delves into the progress made in the application of DED technology to Mg-alloys,its challenges,and ***,the predominant imperfections,notably inhomo

关键词： Additive manufacturing DED processes Arc-DED Wire arc additive manufacturing(waAM) 3-D printing High deposition rate

Recent research in mechanical properties of geopolymer-based ultrahigh-performance concrete:A review

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Defence Technology（防务技术） 2024年第2期32卷 67-88页

作者： g.Murali Division of Research&Innovation Uttaranchal UniversityDehradun 248007India

Due to the growing need for sustainable and ultra-high-strength construction materials,scientists have created an innovative ultra-high-performance concrete called geopolymer based ultra-highperformance concrete(gUHPC).Besides,in the last few decades,there have been a lot of explosions and ballistic attacks around the world,which have killed many civilians and fighters in border *** this context,this article reviews the fresh state and mechanical properties of ***,the ingredients of gUHPC and fresh properties such as setting time and flowability are briefly ***,the review of compressive strength,flexure strength,tensile strength and modulus of elasticity of fibrous ***,the blast and projectile impact resistance performance was ***,the microstructural characteristics were reviewed using the scanning electron microscope and X-ray Powder *** review outcome reveals that the mechanical properties were increased when 30%silica fume was added to a higher dose of steel fibre to improve the microstructure of *** is hypothesized that the brittleness of gUHPC was mitigated by adding 1.5%steel fibre reinforcement,which played a role in the decrease of contact explosion cratering and *** the need for cement in gUHPC was a key factor in the review,indicating a promising potential for lowering carbon ***,gUHPC research is still in its early stages,so more study is required before its full potential can be utilized.

关键词： Mechanical properties Blast Projectile impact Fibre geopolymer Silica fume Alkaline activators

Heavy Metal Remediation in AgoèNyivéLandfill Soils: Enhancing Stability through Organic Amendments

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Open Journal of Applied Sciences 2024年第4期14卷 961-975页

作者： Bassaï Magnoudéwa Bodjona Diyakadola Dihéénane Bafai gado Tchangbedji waste Management Treatment and Valorization Laboratory (GTVD) Faculty of Sciences University of Lom&#233 Lom&#233 Togo

The burial of waste in developing countries, which is often carried out without respect for environmental standards, constitutes a risk of contamination of soils and even groundwater given the toxic elements they contain. The objective of this work is to carry out a study of the retention of heavy metals through the contribution of cattle manure to soil samples from the final Agoè Nyivé landfill in Lomé, Togo. Soil samples from the final landfill were taken from the surface and depth at several locations to form a composite sample. The amendment of the composite sample was carried out with bovine manure on the mock-up in the Laboratory for six months. The determination of the total contents of heavy metals by the atomic absorption spectrophotometer (SAA) on the composite sample showed high contents exceeding the thresholds recommended by the AFNOR NF U 44-041 standard. Sequential extraction on these composite samples showed that the mobile portions of lead, cadmium, copper and zinc are respectively estimated at 78.06%, 50%, 28.89% and 91.59%. The bovine manure used to amend the landfill samples presents physicochemical parameters that can contribute to rendering heavy metals immobile in the soil matrix under natural conditions. The addition of manure initially made it possible to increase the values of pH, electrical conductivity, cation exchange capacity and organic matter, which promote the retention of heavy metals. Secondly, the addition of manure made it possible to reduce the mobile portion of the heavy metals studied;from 78.06% to 14.39% for lead, from 50% to 11.52% for cadmium, from 28.89% to almost 0% for copper and from 91.15% to 80.58% for zinc. The use of cattle manure as an amendment on the composite sample was decisive in reducing the mobility of heavy metals in the polluted soils of the final landfill.

关键词： Pollution Heavy Metals Soil Sequential Extraction Discharge

Nitrogen mineralization in the oldest climax communities in the eastern Mediterranean region

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Journal of Forestry Research 2024年第1期35卷 213-228页

作者： Fatma Selcen Sakar gürcan güleryüz Department of Biology Section Ecology GörükleGraduate School of Natural and Applied ScienceUniversity of Bursa Uludağ16059 NilüferBursaTurkey Department of Biology Section Ecology GörükleFaculty of Science and ArtsUniversity of Bursa Uludağ16059 NilüferBursaTurkey

In this study,we investigated how tree species affect N mineralization in connection to some soil properties and seconder metabolite levels of litter,in the soil of the old-est native forest *** the oldest pure communi-ties of Pinus nigra(PN),Fagus orientalis(FO),and Abies bornmuelleriana(AB)in the mountain range of Mount Uludağ,Bursa,Turkey,annual net yield and N mineraliza-tion in the 0-5-and 5-20-cm soil layers were determined in a field incubation study over 1 *** locations were chosen from 1300 to 1600 m a.s.l.,and moisture content(%),pH,water-holding capacity(%),organic C,total N,and C/N ratio,and annual net mineral N yield of the soil and hydro-lyzed tannic acid and total phenolic compounds in litter were compared for these forest *** had the highest annual net Nmin yield(43.9±4.8 kg ha^(-1) a^(-1)),*** the lowest(30.5±4.2 kg ha^(-1) a^(-1)).Our findings show that in the oldest forest ecosystems,the seasonal soil moisture content and tree species play an essential role in N cycling and that hydrolyzed tannic acids and total phenolic compounds effectively control N *** acid and total phenolics in the litter were found to inhibit nitrification,but total phenolics were found to stimulate ammonification.

关键词： Oldest forest communities Nitrogen mineralization Nitrification Tannic acid Total phenolic Litter