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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 Ya.ian 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 investiga.ional 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 allevia.ion of metabolic dysfunction-associated steatohepa.itis(MASH),the advanced form of MAFLD,and liver fibrosis in phase-3 clinical *** hormone-based pharmacothera.ies not only exhibit va.ied degrees of therapeutic efficacy in mitiga.ing hepa.ic steatosis,inflamma.ion 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 thera.ies may yield synergistic therapeutic *** in-depth studies on the intricate interplay among these metabolic hormones are impera.ive for the development of more effica.ious combina.ion thera.ies,enabling precision management of MAFLD and its associated comorbidities.

关键词： metabolic hormones metabolic dysfunctionassociated steatohepa.itis(MASH) liver fibrosis biopharmaceutical development clinical trials

The earliest evidence for a microblade adapta.ion 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 waNG 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 Conserva.ion 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 migra.ion to and settlement of the *** microblade sites,however,have been systema.ically excavated,especially in the remotest,highest-eleva.ion 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,Loca.ity 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 orienta.ion and two types of microblade cores:wedge-shaped and semi-conical,which are similar to those found throughout North *** Optically Stimulated Luminescence(OSL)da.ing and AMS^(14)C da.ing,the age of ND3 ranges from 11 to 10 *** date range indicates ND3 is the oldest microblade site yet recorded in the remote,high-eleva.ion regions of the TP and thus provides important informa.ion 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 adapta.ion is associated with the first prolonged human occupa.ion of the plateau and that microblades played a significant role in media.ing the risks and fa.ilita.ing the mobility necessary to permanently inha.it the TP.

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

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

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Journal of iron and Steel Research interna.ional 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 Prepara.ion 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 mecha.ical properties are widely used in va.ious fields,and further improvement in their properties is essential to meet the requirements in new-genera.ion 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 ma.imize 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 summa.ized.A compara.ive analysis of the precipita.ion beha.ior of the reinforcing phases with different types as well as the risks and means of controlling their use in service,is *** parameters for the applica.ion of va.ious types of second-phase particles in heat-resistant alloys are provided to support the design and prepara.ion of new ultra.igh-performance heat-resistant alloys.

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

Deuterium distribution and beha.ior 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 Applica.ion Institute of Modern Physics Fudan University School of Mecha.ical Engineering Shanghai Jiao Tong University Department of Materials Science and Engineering University of Wisconsin

Tungsten(W),as a plasma-fa.ing material,is subjected to high fluence plasma,resulting in both ra.ia.ion damage and deuterium(D) *** study explores the blistering beha.ior and D supersaturated layers in both pre-damaged and undamaged W *** achieve a uniform damage profile similar to neutron irra.ia.ion,carbon(C) ions with multiple energies and angles were *** samples were further irra.iated with low-energy D ions under two fluences at temperatures from ～380 to 640 *** va.ious experimental techniques,we found that pre-damaged W samples can effectively suppress the forma.ion 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 correla.ion between blistering and the D supersatura.ion was *** results suggest that neutron irra.ia.ion in the fusion reactors could increase the critical D concentra.ion for blistering,while a greater depth of damage fa.ilitated the inward diffusion of D,thereby reducing the D concentra.ion gra.ient and allevia.ing surface blistering.

关键词： Tungsten Deuterium Supersaturated layer Blister ion irra.ia.ion Pre-damage

Supramolecular Ma.ipula.ion of intracellular a.idic 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 wang Chen Sun Yu Dong Yuan-Fu Ding Chen Zhao ian wa Ho Jiahong Lu Ruibing wang State Key Laboratory of Qua.ity Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 999078China

Lysosomes are the“cell stomach”that digests va.ious species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and ***,artificially ma.ipula.ing intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and ***,a supramolecular strategy to efficiently tether and fuse a.idic 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)deriva.ive dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADa.wa. designed to target intracellular a.idic vesicles via MOR and to decorate their surfaces with ***,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic a.id(Ha.induced supramolecular tethering and fusion of a.idic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of a.idic *** a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstra.ing that supramolecular regula.ion of the dyna.ics of intracellular a.idic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.

关键词： supramolecular chemistry organelle regula.ion intracellular a.idic vesicles lysosomes selfdefense self-repair

Heavy Metal Remedia.ion in AgoèNyivéLandfill Soils: Enhancing Sta.ility through Orga.ic 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 conta.ina.ion 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 loca.ions 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 determina.ion 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, ca.ion exchange capa.ity and orga.ic 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

Physico-Chemical Characteriza.ion of Wood Ash for Agronomic Purposes

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Journal of Agricultural Chemistry and Environment 2024年第2期13卷 235-250页

作者： a.i Kévin Ajavon Bassaï Magnoudéwa Bodjona Diyakadola Dihéénane Bafai Laboratory waste Management Treatment and Recovery (GTVD) Faculty of Sciences University of Lome Lome Togo

The oil refinery of the food products company SOPAL, located in the port area of TOGO, produces an average of 200 kg of eucalyptus wood ash per day. This ash is stored in large quantities within the premises of the refinery, without any disposal solution. The aim of this study is to identify the physico-chemical properties of SOPAL’s wood ash for agronomic valoriza.ion. Physico-chemical analyses reveal the presence of major and secondary elements such as potassium (15.71 g/kg DM), phosphorus (27.90 g/kg DM), calcium (9.76 g/kg DM), magnesium (0.03 g/kg DM), sodium (1.24 g/kg DM), iron (1.49 g/kg DM) and manganese (7.82 g/kg DM). The pH is alka.ine (12.97) with fairly high conductivity (24.10 mS/Cm). Heavy metals identified are cobalt (0.19 mg/kg DM), cadmium (0.10 mg/kg DM), lead (1.14 mg/kg DM), copper (19.77 mg/kg DM) and nickel (12.82 mg/kg DM). The results show that the ash contains considerable amount of major and secondary elements for agronomic uses.

关键词： industry Wood Ash Heavy Metals Valoriza.ion

Comprehensive Overview of Populus simonii Research in the Recent Years

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Open Journal of Ecology 2024年第5期14卷 419-434页

作者： Dandan Zhang Faujiah Nurhasanah Ritonga Tuya Siqin Runxian Song Zicheng Zhang Mingwei Tang Peilin Sun wa Gao Heilongjiang institute of Atomic Energy Harbin China Graduate School Padjadjaran University Bandung Indonesia Key Laboratory of Molecular Epigenetics of the Ministry of Educa.ion Northeast Normal University Changchun China

As an important ecological tree species in northern China, Populus simonii plays a crucial role in maintaining ecological balance and promoting environmental sustaina.ility. The academic community has conducted a series of in-depth studies on this species, covering key areas such as genomics, survival mecha.isms, and genetic breeding. Through the analysis of the genomic structure and function of P. simonii, we have not only revealed the molecular ba.is for its adapta.ion to harsh environments but also identified key genes that promote its growth and resistance to pests and diseases. Furthermore, exploring the survival mecha.isms of P. simonii has deepened our understanding of its stress resistance traits, including how it effectively copes with a.iotic stresses such as drought, sa.iniza.ion, and heavy metal pollution. in genetic breeding, significant progress has been made through the applica.ion of modern biotechnology, improving the growth rate and wood qua.ity of P. simonii and enhancing its environmental adapta.ility and disease resistance. These research findings have not only enriched our knowledge of the biological characteristics of P. simonii but also provided a solid scientific founda.ion for its applica.ion in ecological restora.ion, forestry production, and environmental management.

关键词： Breeding Ecological Restora.ion Genomics Populus simonii Resistance Mecha.isms

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玉米野生种基因组研究进展及应用

生物技术通报 2024年第3期40卷 14-24页

作者：胡伊娃陈露浙江大学农业与生物技术学院作物科学研究所杭州310058

气候变化为粮食生产、生态系统的稳定性带来了重要的挑战。在极端气候变化下,发展适应性物种是作物遗传育种的重要目标之一。作为重要的作物之一,玉米在经历强烈的驯化瓶颈之后,已经丢失了大量的遗传多样性,特别是一些与生物和非生物胁... 详细信息

气候变化为粮食生产、生态系统的稳定性带来了重要的挑战。在极端气候变化下,发展适应性物种是作物遗传育种的重要目标之一。作为重要的作物之一,玉米在经历强烈的驯化瓶颈之后,已经丢失了大量的遗传多样性,特别是一些与生物和非生物胁迫相关的位点。在野生种和农家种中寻找玉米驯化过程中丢失的遗传多样性,并将其应用于现代遗传育种中,将为适应性新品种的创制提供新的契机。本文在对大刍草(玉米野生近亲)的发现及分类研究进行介绍之后,进一步总结了大刍草和玉米的性状与基因组差异,并综述了目前基于遗传学、群体遗传学、分子生物学等对大刍草和玉米之间差异遗传机理剖析的进展,多角度表明了大刍草在玉米遗传学研究中的重要性。最后,对未来气候变化下大刍草在玉米育种中的重要性提出了展望。

关键词：气候变化玉米适应性野生种