Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. ...Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-β-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-β-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-β-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment.
Avian metapneumovirus causes acute respiratory tract infection and reductions in egg production in various avian species. We isolated and characterized an increasingly prevalent avian metapneumovirus ...subgroup C strain from meat-type commercial chickens with severe respiratory signs in China. Culling of infected flocks could lead to economic consequences.
in order to achieve more effective management and monitoring of water environment, an automatic monitoring system is designed for the water environment of Heihe River Basin in Zhangye through GIS ...(geographic information system). The EFDC (environmental fluid dynamics code) model is used to establish the automatic monitoring model of water environment, and the annual average data of permanganate index of Yingluoxia, Gaoya hydrological station, and Liubaqiao in Heihe River Basin from 2015 to 2019 are used to fit and verify the water quality model. The trend suggests that the simulated data of the three observation points are close to the measured data. The fitting degree reveals that the R index of fitting curve of Liubaqiao is 0.793, while that of Yingluoxia, and Gaoya hydrological station is higher than 0.8, with good fitting degree. The average relative error between the simulated value and the measured value of permanganate index (mg/L) is small, the change trend is basically consistent, and the prediction error is small. The model is successfully established and applied to the automatic monitoring and early warning system of total phosphorus index.
Historically, the majority of statistical association methods have been designed assuming availability of SNP-level information. However, modern genetic and sequencing data present new challenges to ...access and sharing of genotype-phenotype datasets, including cost of management, difficulties in consolidation of records across research groups, etc. These issues make methods based on SNP-level summary statistics particularly appealing. The most common form of combining statistics is a sum of SNP-level squared scores, possibly weighted, as in burden tests for rare variants. The overall significance of the resulting statistic is evaluated using its distribution under the null hypothesis. Here, we demonstrate that this basic approach can be substantially improved by decorrelating scores prior to their addition, resulting in remarkable power gains in situations that are most commonly encountered in practice; namely, under heterogeneity of effect sizes and diversity between pairwise LD. In these situations, the power of the traditional test, based on the added squared scores, quickly reaches a ceiling, as the number of variants increases. Thus, the traditional approach does not benefit from information potentially contained in any additional SNPs, while our decorrelation by orthogonal transformation (DOT) method yields steady gain in power. We present theoretical and computational analyses of both approaches, and reveal causes behind sometimes dramatic difference in their respective powers. We showcase DOT by analyzing breast cancer and cleft lip data, in which our method strengthened levels of previously reported associations and implied the possibility of multiple new alleles that jointly confer disease risk.
In the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling ...pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury.
We systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1.
Our findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.
Background Pathological cardiac hypertrophy is regarded as a critical precursor and independent risk factor of heart failure, and its inhibition prevents the progression of heart failure. ...Switch-associated protein 70 (SWAP70) is confirmed important in immunoregulation, cell maturation, and cell transformation. However, its role in pathological cardiac hypertrophy remains unclear. Methods and Results The effects of SWAP70 on pathological cardiac hypertrophy were investigated in
knockout mice and
overexpression/knockdown cardiomyocytes. Bioinformatic analysis combined with multiple molecular biological methodologies were adopted to elucidate the mechanisms underlying the effects of SWAP70 on pathological cardiac hypertrophy. Results showed that SWAP70 protein levels were significantly increased in failing human heart tissues, experimental transverse aortic constriction-induced mouse hypertrophic hearts, and phenylephrine-stimulated isolated primary cardiomyocytes. Intriguingly, phenylephrine treatment decreased the lysosomal degradation of SWAP70 by disrupting the interaction of SWAP70 with granulin precursor. In vitro and in vivo experiments revealed that
knockdown/knockout accelerated the progression of pathological cardiac hypertrophy, while
overexpression restrained the cardiomyocyte hypertrophy. SWAP70 restrained the binding of transforming growth factor β-activated kinase 1 (TAK1) and TAK1 binding protein 1, thus blocking the phosphorylation of TAK1 and downstream c-Jun N-terminal kinase/P38 signaling. TAK1 interacted with the N-terminals (1-192) of SWAP70.
(193-585) overexpression failed to inhibit cardiac hypertrophy when the TAK1-SWAP70 interaction was disrupted. Either inhibiting the phosphorylation or suppressing the expression of TAK1 rescued the exaggerated cardiac hypertrophy induced by
knockdown. Conclusions SWAP70 suppressed the progression of cardiac hypertrophy, possibly by inhibiting the mitogen-activated protein kinases signaling pathway in a TAK1-dependent manner, and lysosomes are involved in the regulation of SWAP70 expression level.
We approach the problem of combining top-ranking association statistics or P-values from a new perspective which leads to a remarkably simple and powerful method. Statistical methods, such as the ...rank truncated product (RTP), have been developed for combining top-ranking associations, and this general strategy proved to be useful in applications for detecting combined effects of multiple disease components. To increase power, these methods aggregate signals across top ranking single nucleotide polymorphisms (SNPs), while adjusting for their total number assessed in a study. Analytic expressions for combined top statistics or P-values tend to be unwieldy, which complicates interpretation and practical implementation and hinders further developments. Here, we propose the augmented rank truncation (ART) method that retains main characteristics of the RTP but is substantially simpler to implement. ART leads to an efficient form of the adaptive algorithm, an approach where the number of top ranking SNPs is varied to optimize power. We illustrate our methods by strengthening previously reported associations of μ-opioid receptor variants with sensitivity to pain.
In order to further understand the impact of industrial mining on the environment, this study conducted environmental monitoring on the radionuclide thorium content in a water body in an industrial ...mining area in Gansu Province, aiming to fully understand the occurrence of radioactive map elements in the area and its impact on the local. The specific impact caused by the ecological environment. The results of this paper are as follows: In the water environment surveyed this time, surface water has the highest content of radioactive thorium at 0.2μg/L, and the lowest concentration of radioactive thorium in groundwater, with an average concentration of 0.04 μg/L. And with the depth of surface water sampling, there is a negative correlation between the content of thorium in the water. This research content can provide sufficient reference materials for the occurrence of thorium in the water in industrial mining areas, and is of great significance to the related research on radioactive elements in the water.
The highly ordered Ti O2nanotubes（NTs） were fabricated by the anodic oxidation method.Their morphology,structure and crystalline phase were characterized by scanning electron microscopy（SEM） and ...X-ray diffractometer（XRD）.The effects of morphology,specific surface area,pore structures and photocatalytic activity of the Ti O2 NTs were investigated.UV–vis spectra analysis showed that its light absorption had been extended to the visible light range.The photocatalytic activity of the as-prepared samples was evaluated by photocatalytic oxidation of gaseous HCHO and MB aqueous solution.The samples had better adhesion strength in the dark and showed a higher photocatalytic activity than nanoparticles.Especially,with ultraviolet light pretreatment,the nanotubes exhibited more stable active for photocatalytic decomposition and the photodecomposition rate remained at high level after 3 cycles of the photocatalysis experiment.Thus,how the number of surface active group ·OH increased and the mechanism for the great improvement for the photocatalytic activity are discussed.
Previous studies demonstrated that Mongolian gerbils can be infected by hepatitis E virus (HEV), which induces the hepatic injury. Here, the mitochondria in hepatocytes from HEV-infected gerbils were ...considerably swollen, thin cristae. After HEV infection, the activity of superoxide dismutase significantly decreased (
< 0.01), while malondialdehyde concentrations significantly increased, compared with those in the control group (
< 0.01). Adenosine triphosphatase levels decreased significantly in the hepatocyte of the inoculated groups, compared with those in control group (
< 0.05) at days 21, 28, 42 post-inoculation (dpi) as well. Furthermore, the levels of ATP synthetase ATP5A1 significantly decreased during HEV infection, compared with those in the control group (
< 0.05). According to the TdT mediated dUTP nick end labeling (TUNEL) detection, TUNEL positive hepatocytes increased in the inoculated group, compared with that in the control group (
< 0.05). Up-regulation of the mitochondrion-mediated apoptosis regulating proteins, Bax and Bcl-2, in the HEV-infected gerbils (
< 0.05) was observed. However, cytochrome c levels in mitochondria decreased, while this molecule was detected in the cytoplasm of the infected animals, in contrast to that in the control group. Apaf-1, and active caspase-9 and -3 levels were shown to be significantly higher in the inoculated group compared with those in the control group (
< 0.05). Taken together, our results demonstrated that HEV infection induces hepatocyte injuries and activity of the mitochondrial apoptotic pathway, which trigger the hepatocyte apoptosis in Mongolian gerbils.
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