Selenogenome and AMPK signal insight into the protective effect of dietary selenium on chronic heat stress-induced hepatic metabolic disorder in growing pigs

Background:Chronic heat stress(CHS)disrupts hepatic metabolic homeostasis and jeopardizes product quality of pigs.Selenium(Se)may regulate the metabolic state through affect selenoprotein.Thus,we investigate the protective effect of dietary hydroxy-4-methylselenobutanoic acid(HMSeBA)on CHS induced hepatic metabolic disorder in growing pigs,and the corresponding response of selenoprotein.Methods:Forty crossbreed growing pigs were randomly assigned to five groups:control group raised in the thermoneutral environment(22±2℃)with basal diet;four CHS groups raised in hyperthermal condition(33±2℃)with basal diet and supplied with 0.0,0.2,0.4,and 0.6 mg Se/kg HMSeBA,respectively.The trial lasted 28 d.The serum biochemical,hepatic metabolism related enzyme,protein and gene expression and 25 selenoproteins in liver tissue were determined by real-time PCR,ELISA and western blot.Results:CHS significantly increased the rectal temperature,respiration rate,serum aspartate aminotransferase(AST)and low-density lipoprotein cholesterol(LDL-C)of pigs,up-regulated hepatic heat shock protein 70(HSP70)and induced lower liver weight,glycogen content,hepatic glucokinase and glutathione peroxidase(GSH-Px).The CHSinduced liver metabolic disorder was associated with the aberrant expression of 6 metabolism-related gene and 11 selenoprotein encoding genes,and decreased the protein abundance of GCK,GPX4 and SELENOS.HMSeBA improved anti-oxidative capacity of liver.0.4 or 0.6 mg Se/kg HMSeBA supplementation recovered the liver weight,glycogen content and rescue of mRNA abundance of genes related to metabolism and protein levels of GCK.HMSeBA supplementation changed expressions of 15 selenoprotein encoding genes,and enhanced protein expression of GPX1,GPX4 and SELENOS in the liver affected by CHS.CHS alone showed no impact while HMSeBA supplementation increased protein levels of p-AMPKαin the liver.Conclusions:In summary,HMSeBA supplementation beyond nutrient requirement mitigates CHS-induced hepatic metabolic disorder,recovered the liver glycogen content and the processes that are associated with the activation of AMPK signal and regulation of selenoproteins in the liver of growing pigs.

Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress

Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by dietary selenium(Se)level.Here,we developed the dietary oxidative stress(DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation,which is accompanied by mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and protein and lipid metabolism disorders.Supplementation with Se(0.3,0.6 or 0.9 mg Se/kg)in form of hydroxy selenomethionine(OH-SeMet)linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins,which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle,and the mitigation of mitochondrial dysfunction and ER stress.What’s more,selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle.However,several parameters such as the activity of GSH-Px and T-SOD,the protein abundance of JNK2,CLPP,SELENOS and SELENOF did not show dose-dependent changes.Notably,several key selenoproteins such as MSRB1,SELENOW,SELENOM,SELENON and SELENOS play the unique roles during this protection.Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress,recover protein and lipid biosynthesis,thus alleviate skeletal muscle growth retardation.Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.

Simulation of the Production Performances of Horizontal Wells with a Fractured Shale Gas Reservoir

The production performances of a well with a shale gas reservoir displaying a complex fracture network are simulated.In particular,a micro-seismic cloud diagram is used to describe the fracture network,and accordingly,a production model is introduced based on a multi-scale flow mechanism.A finite volume method is then exploited for the integration of the model equations.The effects of apparent permeability,conductivity,Langmuir volume,and bottom hole pressure on gas well production are studied accordingly.The simulation results show that ignoring the micro-scale flow mechanism of the shale gas leads to underestimating the well gas production.It is shown that after ten years of production,the cumulative gas production difference between the two scenarios with and without considering the micro-scale flow mechanisms is 19.5%.The greater the fracture conductivity,the higher the initial gas production of the gas well and the cumulative gas production.The larger the Langmuir volume,the higher the gas production rate and the cumulative gas production.With the reduction of the bottom hole pressure,the cumulative gas production increases,but the growth rate gradually decreases.

MKL1基因多态性与高原环境适应性的遗传关联研究

高原环境适应性与遗传因素密切相关,已有多个基因被报道与高原环境适应性显著相关。巨核细胞白血病因子1(megakaryoblastic leukemia 1,MKL1)是一种转录调节因子,在平滑肌细胞的表型调变中发挥重要作用。为探讨MKL1基因是否与高原环境适应性相关,本研究进行了MKL1基因多态性与高原环境适应性的遗传关联分析。本研究招募了世居青藏高原的藏族人群(n=595)和世居平原地区的汉族人群(n=442),并采用MassARRAY阵列图谱技术对MKL1基因的多态性位点rs59098711进行基因分型,比较了其基因型及等位基因型在两组人群中的分布是否存在显著差异。结果发现,在藏、汉两组人群间rs59098711位点的基因型和等位基因型频率存在显著差异(P<0.05)。进一步通过与公共数据库比较发现,藏族人群中rs59098711的基因型及等位基因型的频率分布与其他人种存在显著差异(P<0.05)。生物信息学分析表明,rs59098711位点位于MKL1基因增强子区域,与MKL1基因表达的调控密切相关。同时,基于公共数据集进行的基因差异表达分析发现,MKL1基因在低压性缺氧环境中显著上调。以上研究结果表明,MKL1基因的多态性位点rs59098711与人类的高原适应能力存在相关性。

甲烷氧化菌素研究进展

甲烷氧化菌素(methanobactin,Mbn)最早发现于甲烷氧化菌,是一类由核糖体合成的翻译后修饰肽,其特征是特定的半胱氨酸残基被修饰成恶唑酮-硫代酰胺基团.Mbn对铜离子具有高度亲和性,在甲烷氧化菌的铜稳态生理调控中发挥了重要的作用.近年,在其他种属的细菌中也发现了Mbn操纵子的存在,并根据系统发育分析将其分为五大类(groupsⅠ–Ⅴ).目前已经分离鉴定的Mbn既有结构的保守性,也有序列的特异性.除了铜螯合特性,Mbn还被证明具有氧化酶活性、解汞毒能力以及抑菌作用等,尤其在治疗铜代谢相关疾病、细菌感染性疾病等方面具有潜在的开发价值.本文对Mbn的种类、结构、生物合成机制和生物学功能等方面的研究成果进行综述,并展望其应用前景,旨在为Mbn的开发应用提供理论指导和科学支撑.

Toward atomistic models of intact severe acute respiratory syndrome coronavirus 2 via Martini coarsegrained molecular dynamics simulations

The causative pathogen of coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an enveloped virus assembled by a lipid envelope and multiple structural proteins.In this study,by integrating experimental data,structural modeling,as well as coarse-grained and all-atom molecular dynamics simulations,we constructed multiscale models of SARS-CoV-2.Our 500-ns coarse-grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane-embedded proteins and the surrounding lipid molecules in situ.Our results indicated that the membrane-embedded proteins are highly dynamic,and certain types of lipids exhibit various binding preferences to specific sites of the membrane-embedded proteins.The equilibrated virion model was transformed into atomic resolution,which provided a 3D structure for scientific demonstration and can serve as a framework forfuture exascale allatom molecular dynamics(MD)simulations.A short all-atom molecular dynamics simulation of 255 ps was conducted as a preliminary test for largescale simulationsofthis complexsystem.

Evolution of dielectric loss-dominated electromagnetic patterns in magnetic absorbers for enhanced microwave absorption performances

As the growing criterion of electromagnetic wave (EMW) absorption materials, micro/nano-scale magnetic materials are drawing more and more attention for their unique features compared to bulky absorbers. Generally, the complex permeability of micro/nano-scale magnetic absorbers varies in a relatively narrow range, whatever for the storage of magnetic energy or the dissipation of magnetic energy. If so, how the small variation of permeability affects the ultimate performances is still unclear. Here, a strategy of electromagnetic parameters regulation for the magnetic materials is applied to understand the loss contribution in micro/nanoscale magnetic absorbers. After analyzing the evolution of electromagnetic maps of ten ferrosoferric oxide samples, it can be found that the dissipation contribution of permeability for magnetic materials is weaker than that of permittivity, in spite of its significant role in determining the impedance matching characteristics. In summary, this work systematically explores the loss contribution in micro/nano-magnetic absorbers for the first time, which is of great importance in designing and optimizing the microwave absorption properties of magnetic absorbers.

Numerical Approach for Thermal History Modelling in Multi-Episodic Rifting Basins

Pre-existing models for thermal history modelling have shown deficiency in explicit algorithms to establish the quantitative relationship between maturity indices and thermal gradients in some sedimentary basins that experienced multi-episodic rifting evolution. In this study, a forward and inverse combination model(FICM) is proposed to estimate the vitrinite reflectance(Ro) and thermal gradients. The forward module is used to calculate Ro values. It couples the EASY%Ro model with burial history reconstruction with consideration of thermal gradient variations during basin evolution. The inverse module reconstructs histoical thermal gradients by calibrating cmputed Ro against measured Ro data. The time-temperature series is a necessary input for both forward and inverse modules. Sample density is a profound factor influencing the accuracy of modelling results. In order to obtain satisfying outputs, a sufficient sample density is required. Thermal gradients are assumed to vary linearly between two given samples. Modelling results of case studies indicate that the sensitivity of heating time to Ro evlution is differnt with thermal gradients depending on geolgoical setting. Three difffernt districts, which include the time-sensitive area, the temperature-sensitive area and the non-sensitive area, can be recognized on the the relationship map among Ro variations, heating time and geothermal gradients. This model can be applied to reconstruct the thermal history and maturation evolution in a basin that has undergone complex multi-episodic rifting.

Strategic Thinking on Shallow-water Oil and Gas Exploration in Offshore China

The oil and gas exploration in offshore China has made great achievements,and as the important areas of offshore exploration,the shallow waters contribute most of the oil and gas reserves and production.However,the available area for exploration is diminishing and the cost of exploration is rising.The field changes and ever increasing difficulties of exploration bring new challenges technically and economically.Therefore,for effective exploration of shallow-water oil and gas in offshore China,it is necessary to center on the general requirements of becoming a powerful marine country and the ideas of value exploration,initiate key research projects in the fields of China's offshore stratigraphic-lithologic reserves,Paleogene reserves,buried-hill reserves,high temperature and pressure reserves and hydrocarbon-rich sags,and form geological theories and explorative technologies of large and medium size oil and gas field in offshore China.The measures regarding the challenges include:(1) Innovating theoretical understanding and optimizing new exploration fields,(2) developing technical capabilities and improving the success rate of exploration,and(3) enhancing management level and deepening value exploration.