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Formation pressure gradually decreases with fracturing fluid flowback and gas production. Due to the stress sensitivity of the fractures, the permeability of the artificial fractures after fracturing becomes lower, which significantly affects gas well productivity. This paper focuses on two questions: (1) the stress sensitivity of proppant-containing fractures with different roughness and (2) tight gas well productivity considering stress sensitivity. Two types of artificial fracture samples, smooth and rough, are prepared and filled with different proppant concentrations. Then, the changing confining pressure method is used to quantify sample stress sensitivity. On this basis, the productivity equation for the fractured well with finite conductivity that considers fracture and matrix stress sensitivity is derived, and the influence of stress sensitivity on productivity is discussed. The results show that proppant concentration and fracture surface roughness will significantly affect fracture permeability and stress sensitivity; with increasing proppant concentration, fracture permeability increases, stress sensitivity decreases, and well productivity increases; under the same proppant concentration, the stress sensitivity is lower and the gas production is higher for smooth fracture; and when the artificial fracture changes from no proppant to proppant, the productivity of the fracturing well is improved the most.

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.

The calcium binding protein S100 family in humans contains 21 known members, with each possessing a molecular weight between 10 and 14 kDa. These proteins are characterized by a unique helix-loop-helix EF hand motif, and often form dimers and multimers. The S100 family mainly exists in vertebrates and exerts its biological functions both inside cells as a calcium sensor/binding protein, as well as outside cells. S100A11, a member of the S100 family, may mediate signal transduction in response to internal or external stimuli and it plays various roles in different diseases such as cancers, metabolic disease, neurological diseases, and vascular calcification. In addition, it can function as chemotactic agent in inflammatory disease. In this review, we first detail the discovery of S100 proteins and their structural features, and then specifically focus on the tissue and organ expression of S100A11. We also summarize its biological activities and roles in different disease and signaling pathways, providing an overview of S100A11 research thus far.

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.

Background Obesity plays crucial roles in the pathogenesis of metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes (T2D). The underlying mechanisms linking obesity to metabolic diseases are still less understandable. Methods Previously, we screened a group of spontaneously obese rhesus monkeys. Here, we performed a plasma lipidomic analysis of normal and obese monkeys using gas chromatography/mass spectroscopy (GC/MS) and ultra-high performance liquid chromatography/mass spectroscopy (UPLC/MS). Results In total, 143 lipid species were identified, quantified, and classified into free fatty acids (FFA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), and sphingomyelin (SM). Data analysis showed that the obese monkeys had increased levels of fatty acids palmitoleic acid (C16:1) and arachidonic acid (C20:4), FFA especially palmitic acid (C16:0), as well as certain PC species and SM species. Surprisingly, the plasma level of LPA-C16:0 was approximately four-fold greater in the obese monkeys. Conversely, the levels of most PE species were obviously reduced in the obese monkeys. Conclusion Collectively, our work suggests that lipids such as FFA C16:0 and 16:0-LPA may be potential candidates for the diagnosis and study of obesity-related diseases.

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.

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.

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。