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With the popularization of natural gas and the requirements for environmental protection, the development and utilization of natural gas is particularly important. The status of natural gas in China’s oil and gas exploration and development is constantly improving, and the country is paying more and more attention to the exploitation and utilization of natural gas. The Upper Paleozoic tight sandstone in the Ordos Basin is characterized by low porosity, low permeability and a large area of concealed gas reservoirs. By injecting carbon dioxide into the formation, the recovery rate of natural gas can be improved, and carbon neutrality can be realized by carbon sequestration. Injecting greenhouse gases into gas reservoirs for storage and improving recovery has also become a hot research issue. In order to improve the recovery efficiency of tight sandstone gas reservoirs, this paper takes the complex tight sandstone of the Upper Paleozoic in the Ordos Basin as the research object; through indoor physical simulation experiments, carried out the influence of displacement rate, fracture dip angle, core permeability, core dryness and wetness on CO2 gas displacement efficiency and storage efficiency; and analyzed the influence of different factors on gas displacement efficiency and storage efficiency to improve the recovery and storage efficiency. The research results show that under different conditions, when the injection pore volume is less than 1 PV, the relationship between the CH4 recovery rate and the CO2 injection pore volume is linear, and the tilt angle is 45°. When the injection pore volume exceeds 1 PV, the CH4 recovery rate increases slightly with the increase in displacement speed, the recovery rate of CO2 displacement CH4 is between 87–97% and the CO2 breakthrough time is 0.7 PV–0.9 PV. In low-permeability and low-speed displacement cores, the diffusion of carbon dioxide molecules is more significant. The lower the displacement speed is, the earlier the breakthrough time is, and the final recovery of CH4 slightly decreases. Gravity has a great impact on carbon sequestration and enhanced recovery. The breakthrough of high injection and low recovery is earlier, and the recovery of CH4 is about 3.3% lower than that of low injection and high recovery. The bound water causes the displacement phase CO2 to be partially dissolved in the formation water, and the breakthrough lags about 0.1 PV. Ultimately, the CH4 recovery factor and CO2 storage rate are higher than those of dry-core displacement. The research results provide theoretical data support for CO2 injection to improve recovery and storage efficiency in complex tight sandstone gas reservoirs.

Liver fibrosis is a key transformation stage and also a reversible pathological process in various types of chronic liver diseases. However, the pathogenesis of liver fibrosis still remains elusive. Here, we report that the calcium binding protein A11 (S100A11) is consistently upregulated in the integrated data from GSE liver fibrosis and tree shrew liver proteomics. S100A11 is also experimentally activated in liver fibrosis in mouse, rat, tree shrew, and human with liver fibrosis. While overexpression of S100A11 in vivo and in vitro exacerbates liver fibrosis, the inhibition of S100A11 improves liver fibrosis. Mechanistically, S100A11 activates hepatic stellate cells (HSCs) and the fibrogenesis process via the regulation of the deacetylation of Smad3 in the TGF-β signaling pathway. S100A11 physically interacts with SIRT6, a deacetylase of Smad2/3, which may competitively inhibit the interaction between SIRT6 and Smad2/3. The subsequent release and activation of Smad2/3 promote the activation of HSCs and fibrogenesis. Additionally, a significant elevation of S100A11 in serum is observed in clinical patients. Our study uncovers S100A11 as a novel profibrogenic factor in liver fibrosis, which may represent both a potential biomarker and a promising therapy target for treating liver fibrosis and fibrosis-related liver diseases.

In this paper, the day-ahead optimal dispatching model of power system that is combined by wind-photovoltaic-hydropower-thermal-pumped storage is established. Firstly, according to the characteristics of the short-term hydropower system dispatching problem, a new mathematical model of the cascade hydropower group system with pumped storage power stations is proposed. The coordinated optimized dispatching model of the hydropower group system formed by the cascading of pumped storage power plants and conventional hydropower in the power system is studied. Secondly, the opportunity constraint programming model of forecast error reserve is used to deal with the output uncertainty of wind power and photovoltaic. The randomness and intermittency of renewable energy on the stability of the power system are overcame by the combination of wind-photovoltaic-pumped storage. Thirdly, the model for the joint optimal dispatch of short-term wind, photovoltaic, hydropower and thermal power systems with pumped storage is developed with system economics as the goal. Fourthly, the operation volatility coefficient of thermal power units is proposed to study the impact of renewable energy on the operation of thermal power. Finally, an example system is used to verify the correctness of the proposed dispatching optimal scheduling model, and the results prove that the daily dispatch optimization model proposed in this paper can increase the economic efficiency of the power system by 5%, reduce the start-stop times of thermal power units by 36.55%, and reduce the fluctuation coefficient of the unit by 2.8.

Type 2 diabetes mellitus (T2DM) is a severe metabolic disorder that affects more than 10% of the population worldwide. Obesity is a major cause of insulin resistance and contributes to the development of T2DM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. The nonhuman primate rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individuals of spontaneously diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with a high body mass index at the beginning, but gradually lost their body weight during one year of observation. Furthermore, we performed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. In total, 3,509 proteins were identified and quantified, of which 185 proteins displayed an altered expression level. Gene ontology analysis revealed that the expression of proteins involved in fatty acids β-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation and branched chain amino acid (BCAA) degradation were upregulated in diabetic monkeys. In addition, we observed mild apoptosis in the liver of diabetic monkeys, suggesting liver injury at the late onset of diabetes. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids β-oxidation in obese monkey to BCAA degradation in diabetic monkeys.

The primary function of the nucleolus is ribosome biogenesis, which is an extremely energetically expensive process. Failures in ribosome biogenesis cause nucleolar stress with an altered energy status. However, little is known about the underlying mechanism linking nucleolar stress to energy metabolism. Here we show that nucleolar stress is triggered by inactivation of RSKS-1 (ribosomal protein S6 kinase), RRP-8 (ribosomal RNA processing 8), and PRO-2/3 (proximal proliferation), all of which are involved in ribosomal RNA processing or inhibition of rDNA transcription by actinomycin D (AD), leading to excessive lipid accumulation in Caenorhabditis elegans. The transcription factor PHA-4/FoxA acts as a sensor of nucleolar stress to bind to and transactivate the expression of the lipogenic genes pod-2 (acetyl-CoA carboxylase), fasn-1 (fatty acid synthase), and dgat-2 (diacylglycerol O-acyltransferase 2), consequently promoting lipid accumulation. Importantly, inactivation of pha-4 or dgat-2 is sufficient to abolish nucleolar stress-induced lipid accumulation and prolonged starvation survival. The results revealed a distinct PHA-4-mediated lipogenesis pathway that senses nucleolar stress and shifts excessive energy for storage as fat., Nucleolar stress can disrupt ribosome biogenesis and in turn energy metabolism and lipid storage, but how this is regulated is unclear. Here, the authors show in C. elegans that the transcription factor PHA-4/FOXA acts as a sensor for nucleolar stress and can regulate expression of lipogenic genes

Non-alcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR) and type 2 diabetes (T2D), for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4) corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD., Summary: This study suggests that the tree shrew (Tupaia belangeri chinensis) may be useful as a novel animal model for the research of human non-obese non-alcoholic fatty liver disease (NAFLD).

Steroid hormones play essential roles for living organisms. It has been long and well established that the endoplasmic reticulum (ER) and mitochondria are essential sites for steroid hormone biosynthesis because several steroidogenic enzymes are located in these organelles. The adrenal gland lipid droplet (LD) proteomes from human, macaque monkey, and rodent are analyzed, revealing that steroidogenic enzymes are also present in abundance on LDs. The enzymes found include 3β-hydroxysteroid dehydrogenase (HSD3B) and estradiol 17β-dehydrogenase 11 (HSD17B11). Analyses by Western blot and subcellular localization consistently demonstrate that HSD3B2 is localized on LDs. Furthermore, in vitro experiments confirm that the isolated LDs from HeLa cell stably expressing HSD3B2 or from rat adrenal glands have the capacity to convert pregnenolone to progesterone. Collectively, these data suggest that LDs may be important sites of steroid hormone metabolism. These findings may bring novel insights into the biosynthesis and metabolism of steroid hormones and the development of treatments for adrenal disorders.

After decades of research, pancreatic cancer is still a devastating disease. The aim of this article was to assess the efficacy and safety of combination chemotherapy with gemcitabine (GEM) and S-1 (GS) therapy compared with GEM alone therapy in patients with locally advanced or metastatic pancreatic cancer.Relevant trials were identified by searching databases. Five trials were selected in this article. The indicators we used were overall response rate, disease control rate, 1-year survival rate and haematological toxicities.Meta-analysis of the pooled data demonstrated that the overall response rate (risk ratio, RR = 2.52, 95% confidence interval, CI: 1.85-3.42, P 0.00001) and disease control rate (RR = 1.24, 95% CI: 1.12-1.37, P 0.0001) were significantly different for the GS and GEM alone chemotherapies. Among the group of patients, 43.4% in the GS group and 31.4% in the GEM group survived more than a year. According to this, patients who use the GS regiment may have a better prognosis than the GEM regiment (RR = 1.62, 95% CI: 1.12-2.33, P = 0.04). The combination chemotherapy with GEM and S-1 group had higher haematological toxicities including neutropaenia (RR = 1.58, 95% CI: 1.17-2.14, P = 0.003) and thrombocytopaenia (RR = 1.85, 95% CI: 1.28-2.67, P = 0.001). The incidence of anaemia was much the same in the two groups (RR = 1.22, 95% CI: 0.87-1.70, P = 0.24).Overall response rate and disease control rate as well as 1-year survival rate in patients who received GS were superior to those treated with GEM alone. Combination chemotherapy with GEM and S-1 may offer greater benefits in the treatment of pancreatic cancer than GEM alone, although the GS group had higher haematological toxicities. Combination chemotherapy with GEM and S-1 might be an option of first-line chemotherapy for pancreatic cancer patients, at least in Asia. Mini Abstract: This systematic review analysing randomized controlled trials (RCTs) comparing S-1 combination chemotherapy versus GEM alone for locally advanced and metastatic pancreatic cancer demonstrated greater efficacy for S-1 combination in term of response, disease control and 1-year survival proportion.

The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.

Determining the liver changes during the early stages of diabetes is critical to understand the nature of the disease and development of novel treatments for it. Advances in the use of animal models and next-generation sequencing technologies offer a powerful tool in connection between liver changes and the diabetes. Here, we created a tree shrew diabetes model akin to type 1 diabetes by using streptozotocin to induce hyperglycemia and hyperlipidemia. Using RNA-seq, we compiled liver transcriptome profiles to determine the differentially expressed genes and to explore the role of hyperglycemia in liver changes. Our results, respectively, identified 14,060 and 14,335 genes in healthy tree shrews and those with diabetes, with 70 genes differentially expressed between the two groups. Gene orthology and KEGG annotation revealed that several of the main biological processes of these genes were related to translational processes, steroid metabolic processes, oxidative stress, inflammation, and hypertension, all of which are highly associated with diabetes and its complications. These results collectively suggest that STZ induces hyperglycemia in tree shrew and that hyperglycemia induced oxidative stress led to high expression of aldose reductase, inflammation, and even cell death in liver tissues during the early stage of diabetes.

Animal models are indispensible to investigate the pathogenesis and treatments of non-alcoholic fatty liver diseases (NAFLD). Altered cholesterol metabolism has been implicated into the pathogenesis of NAFLD. Here, using high fat, cholesterol and cholate diet (HFHC), we generated a novel tree shrew (Tupaia belangeri chinensis) model of NAFLD, which displayed dyslipidemia with increased levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and high density lipoprotein-cholesterol (HDL-c), but decreased level of triglycerides (TG). Liver histopathology and genes expression indicated that HFHC diet successfully induced liver steatosis to inflammation and fibrosis progressively within 10 weeks. Moreover, HFHC induced the transcriptional expression of lipoprotein lipase (lpl) in the liver, but repressed the expression of LDL receptor and the endogenous synthesis pathway and excretion of cholesterol. Notably, Poloxamer 407 (P-407) inhibition of LPL improved the severity of steatosis and reduced inflammation. These results illustrated that LPL plays an important role in cholesterol metabolism in NAFLD and the tree shrew may be a valuable animal model for further research into NAFLD.

Multi-point disturbance detection is always challenging in polarization-sensitive optical time domain reflectometry (POTDR). In this paper, we propose a novel method to solve such a challenging problem by accumulating the temporally differentiated OTDR traces and building up a two-dimensional temporally-spatially evolving graph, and then using edge detection and automatic-clustering, adopted from imaging processing techniques, to discriminate different disturbance points and find out their locations. Many multi-point disturbance cases are tested and the results show that the method proposed has better performance than the conventional direct differentiation method and the Fast Fourier Transform (FFT) spectrum analysis. In particular, the location accuracy has been improved significantly.

Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi-enzyme system works for distinct desaturases. The model organism Caenorhabditis elegans contains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductases hpo-19 and T05H4.4 led to increased levels of C18:1n-9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs in C. elegans.

Phase-( Φ -) and Polarization- sensitive (P-) Optical-Time-Domain Reflectometries (OTDRs) are both representative optical fiber fence technologies, which have promising applications in long or ultra-long perimeter security with precise location ability. However, the challenge is that they are liable to be interfered by environmental influences due to their high sensitivity feature. Real human intrusions are always buried in the environmental noises and interferences, which lead to poor detection results. Thus it is proposed in this paper to extract human intrusion signals and separate the complicated noisy backgrounds by using a multi-scale Wavelet decomposition method. Practical test results prove its effectiveness.

With the growing demand for monitoring length and channel number of the fully distributed optical fiber sensors (DOFSs), the amount of sensing data is increasing rapidly, and there will be a heavy pressure for the massive data storage and transmission. In this paper, two lossless compression algorithms of Lempel-Ziv-Welch (LZW) and Huffman are comparatively studied to effectively compress the huge amount of data of typical DOFSs, e.g. Φ -OTDR, POTDR, and BOTDA systems. The comparison results show that the LZW based on dictionary has a better performance in the consuming time and compression ratio for the DOFS data.

Stearoyl-CoA desaturase (SCD) is a key enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs) in the biosynthesis of fat. To date, two isoforms ofscdgene (scd1andscd5) have been found widely existent in most of the vertebrate animals. However, the evolutionary patterns of both isofoms and the function ofscd5are poorly understandable. Herein, we aim to characterize the evolutionary pattern ofscdgenes and further predict the function differentiation ofscdgenes. The sequences ofscdgenes were highly conserved among eukaryote. Phylogenetic analysis identified two duplications ofscdgene early in vertebrate evolution. The relative rate ratio test, branch-specificdN/dSratio tests, and branch-sitedN/dSratio tests all suggested that thescdgenes were evolved at a similar rate. The evolution ofscdgenes among eukaryote was under strictly purifying selection though several sites inscd1andscd5were undergone a relaxed selection pressure. The variable binding sites by transcriptional factors at the 5′-UTR and by miRNAs at 3′-UTR ofscdgenes suggested that the regulators ofscd5may be different from that ofscd1. This study promotes our understanding of the evolutionary patterns and function of SCD genes in eukaryote.

The aim of this study was to induce type 2 diabetes in tree shrew (Tupaia belangeri chinensis). Streptozotocin (STZ), a glucosamine derivative of nitrosourea and preferentially toxic to pancreatic beta cells, has been commonly used to induce type 1 and 2 diabetes in experimental animals. Tree shrews were treated with different low doses of STZ (60, 70, and 80 mg/kg), with six control tree shrews receiving citrate buffer. After STZ injection, tree shrews displayed increased fasting blood and urine glucose, impaired oral glucose tolerance test, and disturbed lipids metabolism and renal function. However, STZ induced tree shrews showed no diabetic complications such as diabetic lactic acidosis and hyperglycemic hyperosmolar. Animals with the above type 2 diabetic-like symptoms were variable across the three groups from 66.7% to 100%, and mortality ranged from 16.7% to 33.3%. Thus, two 80 mg/kg STZ dose injections were appeared more appropriate than other doses to induce tree shrew model of type 2 diabetes. Our results demonstrated that type 2 diabetes could be induced with favorable STZ application in tree shrew.链脲佐菌素 (streptozotocin, STZ)是链球菌产生的天然化合物, 对哺乳动物的胰岛B细胞有特异毒性, 被广泛用于诱导1型和2型糖尿病。该研究通过多次小剂量注射STZ来建立树鼩2型糖尿病动物模型。24只树鼩被分为对照组以及60、70和80 mg/kg剂量STZ诱导组。注射STZ后, 成模树鼩出现明显的多饮、多食和多尿症状, 平均体重未减轻, 高血糖症状持续8～16周, 尿糖显著阳性, 肾功能及糖耐受明显受损, 糖脂代谢紊乱, 但未出现糖尿病乳酸中毒和高血糖高渗等并发症。该结果表明, 多次小剂量STZ注射可诱导树鼩出现类似2型糖尿病症状和糖尿病肾脏损伤, 且综合考虑STZ注射次数、成模率以及成模稳定性, 两次注射80 mg/kg剂量的STZ较适合用于创建树鼩2型糖尿病模型。