Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white ...fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.
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•The interactions between resveratrol and gut microbiota on hepatic steatosis are investigated.•The fecal microbiota transplantation is used to investigate the ...interactions.•Resveratrol can reverse high-fat-diet induced dysbiosis.•Resveratrol can ameliorate the hepatic steatosis by regulating gut microbiota.
To investigate whether resveratrol could ameliorate the hepatic steatosis in high-fat diet (HFD) fed mice by modulating gut microbiota composition, fecal microbiota transplantation (FMT) was utilized in this study. Our results showed that resveratrol significantly ameliorated hepatic steatosis in HFD mice, increased the gene expression of fasting-induced adipose factor, and decreased the expression of lipogenesis-related genes and proteins (SREBP-1, FAS and ACC). In addition, resveratrol reversed HFD-induced gut microbiota dysbiosis, with an increase in the relative abundance of Bacteroidetes and a decrease in that of Firmicutes and Proteobacteria. Subsequent results showed the gut microbiota compositions of FMT recipient groups were similar to those of corresponding donor groups. And the changes of state of hepatic steatosis and expression of SREBP-1, ACC and FAS were coordinated with the results of gut microbiota. In conclusion, these results provided evidence to support the resveratrol could ameliorate the hepatic steatosis by modulating the gut microbiota.
Browning of white adipose tissues (WAT) is recognized as a novel way to combat obesity and its related comorbidities. Thus, a lot of dietary agents contributing to browning of WAT have been ...identified.
In this study, we try to explore the mechanism of the browning of WAT induced by resveratrol (Res) in 3T3-L1 adipocytes.
The levels of cell viability and lipid accumulation were evaluated under different concentrations of Res. Cell signaling pathway analysis was performed to investigate the possible mechanisms of the WAT browning effect of Res in 3T3-L1 cells.
We found that Res induced the brown fat-like phenotype by activating protein expressions of brown adipocyte-specific markers, such as peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). Besides, Res reduced lipid accumulation, as shown by Oil Red O staining. The increased small lipid droplets implied that Res-treated 3T3-L1 adipocytes had some features of brown adipocytes. The brown fat-like phenotype in 3T3-L1 adipocytes induced by Res was possibly mediated by activation of mammalian target of rapamycin (mTOR), as brown adipocyte-specific markers were decreased by rapamycin, an inhibitor of mTOR and the MHY1485 treatment, an activator of mTOR, showed the similar effect of Res on browning markers.
Res induced brown-like adipocyte phenotype in 3T3-L1 adipocytes partly via mTOR pathway, which provided new insights into the utilization of Res to prevent obesity and related comorbidities.
Objectives:
To identify the differences of clinical characteristics and outcomes of severe pneumonia in children under 5 years old with and without adenovirus infection.
Methods:
A retrospective ...cohort study was conducted in three pediatric hospitals in Guangzhou, China. In total, 1,595 children under the age of 5 with WHO-defined severe pneumonia had adenovirus testing performed between January 1, 2009 and December 31, 2019. Demographics, complications, the first routine laboratory findings, therapeutic records, and clinical outcome were collected from electronic medical records. We compared characteristics of children with and without adenovirus infection.
Results:
Adenovirus was detected in 75 (4.7%) out of 1,595 children with severe pneumonia. Cases with adenovirus infection were more likely to be boys (74.7 vs. 63.0%), older than 1 year old (78.7 vs. 25.1%), but less likely to have mixed virus infections (25.3 vs. 92.9%) and combined with cardiovascular disease (12.0 vs. 39.7%), and had more abnormal laboratory results than cases without adenovirus infection. Antiviral therapy (4.9%) was rarely used in children with severe pneumonia, but antibiotic therapy (65.3%) was commonly used, especially in cases with adenovirus infection (91.9%). Children infected with adenovirus (9.3 vs. 2.5%) were also hospitalized longer and had a higher mortality within 30 days of hospitalization.
Conclusions:
Children with severe pneumonia under 5 years old with adenovirus infection had more abnormal laboratory findings and more severe clinical outcomes than cases without adenovirus infection. More attention should be focused on the harm caused by adenovirus infection.
Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate ...castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.
Single-cell sequencing datasets are key in biology and medicine for unraveling insights into heterogeneous cell populations with unprecedented resolution. Here, we construct a single-cell multi-omics ...map of human tissues through in-depth characterizations of datasets from five single-cell omics, spatial transcriptomics, and two bulk omics across 125 healthy adult and fetal tissues. We construct its complement web-based platform, the Single Cell Atlas (SCA, www.singlecellatlas.org ), to enable vast interactive data exploration of deep multi-omics signatures across human fetal and adult tissues. The atlas resources and database queries aspire to serve as a one-stop, comprehensive, and time-effective resource for various omics studies.
Hepatocellular carcinoma (HCC) remains a medical challenge due to its high proliferation and metastasis. Although deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation, ...their pathological roles in HCC have not been fully elucidated.
By using biomass spectrometry, co-immunoprecipitation, western blotting and immunofluorescence assays, we identify ribosomal protein S16 (RPS16) as a key substrate of ubiquitin-specific peptidase 1 (USP1). The role of USP1-RPS16 axis in the progression of HCC was evaluated in cell cultures, in xenograft mouse models, and in clinical observations.
We show that USP1 interacts with RPS16. The depletion of USP1 increases the level of K48-linked ubiquitinated-RPS16, leading to proteasome-dependent RPS16 degradation. In contrast, overexpression of USP1-WT instead of USP1-C90A (DUB inactivation mutant) reduces the level of K48-linked ubiquitinated RPS16, thereby stabilizing RPS16. Consequently, USP1 depletion mimics RPS16 deficiency with respect to the inhibition of growth and metastasis, whereas transfection-enforced re-expression of RPS16 restores oncogenic-like activity in USP1-deficient HCC cells. Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients.
These findings reveal a previously unrecognized role for the activation of USP1-RPS16 pathway in driving HCC, which may be further developed as a novel strategy for cancer treatment.
Barrel distortion rectification aims at removing the radial distortion in a distorted image captured by a wide-angle lens. Previous deep learning methods mainly solve this problem by learning the ...implicit distortion parameters or the nonlinear rectified mapping function in a direct manner. However, this type of manner results in an indistinct learning process of rectification and thus limits the deep perception of distortion. In this paper, inspired by the curriculum learning, we analyze the barrel distortion rectification task in a progressive and meaningful manner. By considering the relationship among different construction levels in an image, we design a multi-level curriculum that disassembles the rectification task into three levels, structure recovery, semantics embedding, and texture rendering. With the guidance of the curriculum that corresponds to the construction of images, the proposed hierarchical architecture enables a progressive rectification and achieves more accurate results. Moreover, we present a novel distortion-aware pre-training strategy to facilitate the initial learning of neural networks, promoting the model to converge faster and better. Experimental results on the synthesized and real-world distorted image datasets show that the proposed approach significantly outperforms other learning methods, both qualitatively and quantitatively.
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