Inflammation is the main contributor for the pathogenesis of nonalcoholic steatohepatitis (NASH). Src homology region 2 domain‐containing phosphatase 1 (SHP‐1, also known as PTPN6) is regarded as a ...negative regulator of inflammation, but its role in NASH remains unknown. Here, hepatocyte‐specific Ptpn6 knockout mice (Ptpn6HKO) and adenovirus vector‐mediated ectopic expression of SHP‐1 (AdSHP1) were used to evaluate the role of SHP‐1 in a methionine‐ and choline‐deficient diet‐induced NASH model. Compared with the control littermates, Ptpn6HKO mice show exacerbated hepatic steatosis, inflammation, and fibrosis. Additionally, administration of AdSHP1 significantly ameliorates steatohepatitis and inhibits the expression of proinflammatory cytokines, including transforming growth factor‐β, interleukin‐6, and tumor necrosis factor‐α. Our data indicate that SHP‐1 could be a potential therapeutic target for NASH.
A new LMS algorithm is proposed to improve the accuracy of the sparse system identification with impulse interference. The algorithm adopts a scaler to filter impulse interference, the scalar is also ...used for identifying sparse systems. The adaptive iteration can avoid significant changes since the abrupt impulsive interference in the channel estimation. Furthermore, the proposed method searches the sparse solution by considering the system sparsity and using an approximated
ℓ
0
norm constraint. Because the proposed method combines sparse constraint and impulse interference, it gradually adjusts the step size according to the gradient. The effectiveness and superiority of the proposed algorithm are confirmed for sparse system identification with impulse interference in simulations.
Exploring efficient and reliable catalysts to achieve gasification of biomass waste is a promising research endeavour. In this study solid waste red mud (RM, an inexpensive and efficient support) ...loaded Ni-Cu metals (Ni-Cu/RM) was used to catalyze hydrothermal gasification of cotton stalk at 340–400 ℃ and 16–30 MPa. In the presence of Ni-Cu/RM catalyst, 21.88 mmol/g H2 yield with 79.89% carbon balance was achieved, increased by 22.8 times under the optimized conditions (380 ℃ for 5 min) based on orthogonal experiments. Under the optimal conditions, H2 yield with neat Ni and Ni/RM loaded on RM is 0.96 and 12.94 mmol/g, respectively due to the specific surface area soaring by 72.0 times from 0.7 to 50.5 m2/g. With Ni-Cu/RM bimetallic catalyst, H2 yield jumped from 3.41 to 21.88 mmol/g, 6.7 times higher than that neat Ni, or reached 84% with Ni-Cu/Al2O3 if Al2O3 was as support. It is further found that Cu promoted the dispersion of Ni on red mud with surface area rising from 50.47 to 73.42 m2/g together with forming Ni-Cu alloy (alkalinity of Ni-Cu/RM rose to 285.65 from 172.21 μmol/g for Ni/RM) enhanced H2 generation. When temperature grew from 340 ℃ to 400 ℃ (supercritical), H2 yield improved by 3 times from 9.21 to 28.50 mmol/g. Red mud is an ideal candidate for replacing the commercial support Al2O3.
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•Red mud loaded Ni/Cu catalyst was used for hydrothermal gasification of cotton stalk.•H2 yield improved 3 times from 9.21 to 28.50 mmol/g with temperature from 340 to 400 ℃.•Under optimized conditions, H2 yield was 21.88 mmol/g and carbon balance reached 79.89%.•H2 yield using Ni-Cu/RM was 22.8 times greater than without catalyst (0.96 mmol/g).•Cu increased alkalinity of Ni/RM catalyst (285.65 μmol/g versus 172.21 μmol/g).
When it comes to the application of the photon data gathered by the Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2), accurately removing noise is crucial. In particular, conventional denoising ...algorithms based on local density are susceptible to missing some signal photons when there is uneven signal density distribution, as well as being susceptible to misclassifying noise photons near the signal photons; the application of deep learning remains untapped in this domain as well. To solve these problems, a method for extracting signal photons based on a GoogLeNet model fused with a Convolutional Block Attention Module (CBAM) is proposed. The network model can make good use of the distribution information of each photon’s neighborhood, and simultaneously extract signal photons with different photon densities to avoid misclassification of noise photons. The CBAM enhances the network to focus more on learning the crucial features and improves its discriminative ability. In the experiments, simulation photon data in different signal-to-noise ratios (SNR) levels are utilized to demonstrate the superiority and accuracy of the proposed method. The results from signal extraction using the proposed method in four experimental areas outperform the conventional methods, with overall accuracy exceeding 98%. In the real validation experiments, reference data from four experimental areas are collected, and the elevation of signal photons extracted by the proposed method is proven to be consistent with the reference elevation, with R2 exceeding 0.87. Both simulation and real validation experiments demonstrate that the proposed method is effective and accurate for extracting signal photons.
Peritonitis caused by nontuberculous mycobacterium (NTM) is an important complication in peritoneal dialysis (PD) patients.
Cases of PD complicated by NTM peritonitis reported in the English language ...literature were identified in the PubMed database. The characteristics of these cases were reviewed.
In 41 articles, we identified 57 cases of PD-associated NTM peritonitis in patients ranging from 5 to 82 years. The prevalent clinical findings of these cases were fever, abdominal pain, cloudy fluid and an elevated leukocyte count in peritoneal fluid. These findings were non-specific and could not be differentiated from symptoms caused by Mycobacterium tuberculosis or other bacteria. The majority of these cases received empirical antibacterial therapy before diagnosis of NTM peritonitis. Isolates in more than half of the peritonitis cases were the rapidly growing Mycobacterium, Mycobacterium fortuitum (38.6%) and Mycobacterium chelonae (14.0%). In most cases, PD catheters were removed and experience with non-removal was limited.
Diagnosis of NTM infection should be considered in PD patients with peritonitis that are culture negative or refractory to empirical antibiotic therapy.
Oleanolic acid has previously been shown to possess PI3K inhibitory activity, thus, the purpose of this work was to generate a series of derivatives that improve the potency. Twenty rationally ...designed oleanolic acid derivatives were synthesized and tested the cytotoxicity and PI3K inhibitory activity. The results suggested that attachment of additional structural elements such as association of thiazole group to A ring and insertion of phenylurea group was important for increasing activities. The most active derivative was compound II
2
, which exhibited PI3K inhibitory activity (IC
50
= 58.42 nmol/l) and improved interaction with activity site of PI3K according with docking studies.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abundant in organic matter, the lower Silurian Longmaxi shale in the Upper Yangtze Platform, South China, has been demonstrated to play important roles in the petroleum system as both a good source ...rock and a shale gas reservoir. In order to better understand the heterogeneous organic matter accumulation of such shales in the southeastern Chongqing area, the vertical variations of total organic carbon (TOC) contents, mineral concentrations and biomarker distributions were systematically analyzed in this study. The Longmaxi Formation consists of fine-grained siliciclastic rocks deposited in a restricted marine shelf environment, and it can be further subdivided into two members. The lower member is enriched in TOC, whereas a diminished TOC content is documented in the upper member. Laterally, the TOC content gradually drops southeast-ward in the study area. The mineralogical compositions, dominated by quartz and clay, and, to a lesser extent, feldspar and carbonate, show good correlations with TOC contents vertically, especially in the lower member. Saturated and aromatic hydrocarbon biomarkers indicate a dominant organic matter origin from lower hydrobionts (algae and bacteria) in a reducing marine environment. Negative correlation relationships between TOC contents and terrigenous clastic minerals indicate the predominant role of dilution of terrigenous clastic materials in controlling the organic matter accumulation. The sea level drop combined with the continuously active Xuefeng Uplift contributed to more terrigenous clastic inputs into the study area, which resulted in a significant reduction of TOC content in the upper Longmaxi member.
•Characteristics of organic geochemistry and mineralogy of the Longmaxi Shale were analyzed.•The organic matter mainly originates from lower hydrobiont in a reducing marine environment.•Good correlations exist between TOC content and mineralogical compositions.•The organic matter accumulation is predominantly controlled by the dilution of terrestrial clastics.
Proteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval ...invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved.
TsTryp with C-terminal domain was cloned and expressed in Escherichia coli BL21 (DE3), and the rTsTryp had the enzymatic activity of natural trypsin, but it could not directly degrade gut tight junctions (TJs) proteins. qPCR and western blotting showed that TsTryp was highly expressed at the invasive IIL stage. Immunofluorescence assay (IFA), ELISA and Far Western blotting revealed that rTsTryp specifically bound to IECs, and confocal microscopy showed that the binding of rTsTryp with IECs was mainly localized in the cytomembrane. Co-immunoprecipitation (Co-IP) confirmed that rTsTryp bound to protease activated receptors 2 (PAR2) in Caco-2 cells. rTsTryp binding to PAR2 resulted in decreased expression levels of ZO-1 and occludin and increased paracellular permeability in Caco-2 monolayers by activating the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. rTsTryp decreased TJs expression and increased epithelial permeability, which could be abrogated by the PAR2 antagonist AZ3451 and ERK1/2 inhibitor PD98059. rTsTryp facilitated larval invasion of IECs, and anti-rTsTryp antibodies inhibited invasion. Both inhibitors impeded larval invasion and alleviated intestinal inflammation in vitro and in vivo.
TsTryp binding to PAR2 activated the ERK1/2 pathway, decreased the expression of gut TJs proteins, disrupted epithelial integrity and barrier function, and consequently mediated larval invasion of the gut mucosa. Therefore, rTsTryp could be regarded as a potential vaccine target for blocking T. spiralis invasion and infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•We model a dynamic game demonstrating the price war in industrial land transfer.•Inter-regional competition has resulted in low industrial land price strategy.•The low industrial land price policy ...results in urban sprawl.•To establish a cooperative partnership between the inter-regions is necessary.
China is experiencing rapid progress in industrialization, with its own rationale toward industrial land development based on a deliberate change from an extensive to intensive form of urban land use. One result has been concerted attempts by local government to attract foreign investment by a low industrial land price strategy, which has resulted in a disproportionally large amount of industrial land within the total urban land use structure at the expense of the urban sprawl of many cities. This paper first examines “Comparable Benchmark Price as Residential land use” (CBPR) as the theoretical basis of the low industrial land price phenomenon. Empirical findings are presented from a case study based on data from Jinyun County, China. These data are analyzed to reveal the rationale of industrial land price from 2000 to 2010 concerning the CBPR model. We then explore the causes of low industrial land prices in the form of a “Centipede Game Model”, involving two neighborhood regions as “major players” to make a set of moves (or strategies). When one of the players unilaterally reduces the land price to attract investment with the aim to maximize profits arising from the revenues generated from foreign investment and land premiums, a two-player price war begins in the form of a dynamic game, the effect of which is to produce a downward spiral of prices. In this context, the paradox of maximizing profits for each of the two players are not accomplished due to the inter-regional competition of attracted investment leading to a lose-lose situation for both sides’ in competing for land premium revenues. A short-term solution to the problem is offered involving the establishment of inter-regional cooperative partnerships. For the longer term, however, a comprehensive reform of the local financial system, more adroit regional planning and an improved means of evaluating government performance is needed to ensure the government's role in securing pubic goods is not abandoned in favor of one solely concerned with revenue generation.
In this work, the fatigue crack growth (FCG) behavior and fatigue damage mechanism of the 2.25Cr1Mo0.25V steel welded joint used in hydrogenation reactors were investigated. The multi-pass welding ...was carried out to manufacture the welded joint using the combined shielded metal arc welding (SMAW) and submerged automatic arc welding (SAAW) processes. The FCG behavior of different zones in the welded joint, including the base metal (BM), the heat-affected zone (HAZ) and the weld metal (WM), were studied by compact tension tests. Moreover, the acoustic emission (AE) technique was used to monitor AE signals generated from FCG process for further understanding FCG behavior and fatigue mechanisms. Additionally, the microstructures and fracture surfaces of different specimens were observed by optical microscopy (OM) and scanning electron microscopy (SEM). The results revealed that the microstructure of BM is fine granular bainite, while the WM shows coarser bainite grains. The HAZ exhibits the most significant inhomogeneity with large dispersion of grain size. FCG results showed that the HAZ exhibits much higher fatigue crack growth rate (FCGR) at low Δ
values, while the BM shows the most superior fatigue resistance. The AE technique is successful in monitoring and identifying damage evolutions during the FCG process. Moreover, an enhanced AE activity is observed in FCG of the WM specimen, which is attributed to the combined influence of the formation of numerous secondary cracks and coarse-grained microstructures.
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