Cardiac fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Cardiac fibroblast activation is a key effector of cells resulting in diabetic cardiac fibrosis. ...However, the underlying mechanism of cardiac fibroblast activation and diabetic cardiac fibrosis remains unclear. Accumulating evidence suggests that DNA methylation alterations play a central role in cardiac fibroblast activation. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1)‐mediated suppression of cytokine signaling 3 (SOCS3) promoter hypermethylation leads to downregulation of SOCS3 expression in diabetic cardiac fibrosis. High glucose‐induced expression of DNMT1 was increased in cardiac fibroblasts, while the expression of SOCS3 was decreased. Downregulation of SOCS3 facilitated activation of STAT3 to promote cardiac fibroblast activation and collagen deposition. Genetic or pharmacological inactivation of DNMT1 reversed the activated phenotype of cardiac fibroblasts. Clinically, we observed a significant inverse correlation between DNMT1 and SOCS3 expression levels, and loss of SOCS3 expression or increased expression of DNMT1. Taken together, these findings identify DNMT1 silencing of SOCS3 axis as a driver of cardiac fibroblast activation in diabetic cardiac fibrosis. These results provide a scientific and new explanation of the underlying mechanism of diabetic cardiac fibrosis.
1.DNA methyltransferase 1 (DNMT1) deregulation of suppression of cytokine signaling 3 (SOCS3) axis drivers cardiac fibroblasts activation in diabetic cardiac fibrosis.
2.Downregulation of SOCS3 facilitated activation of STAT3 to promote cardiac fibroblast activation and collagen deposition.
Human actions are often captured by multiple cameras (or sensors) to overcome the significant variations in viewpoints, background clutter, object speed, and motion patterns in video surveillance, ...and action recognition systems often benefit from fusing multiple types of cameras (sensors). Therefore, adaptive fusion of the information from multiple domains is mandatory for multiview human action recognition. Two widely applied fusion schemes are feature-level fusion and score-level fusion. We point out that limitations still exist and there is tremendous room for improvement, including the separate computation of feature fusion and action recognition, or the fixed weights for each action and each camera. However, previous fusion methods cannot accomplish them. In this paper, inspired by nature, the above limitations are addressed for multiview action recognition by developing a novel adaptive fusion and category-level dictionary learning model (abbreviated to AFCDL). It can jointly learn the adaptive weight for each camera and optimize the reconstruction of samples toward the action recognition task. To induce the dictionary learning and the reconstruction of query set (or test samples), the induced set for each category is built, and the corresponding induced regularization term is designed for the objective function. Extensive experiments on four public multiview action benchmarks show that AFCDL can significantly outperforms the state-of-the-art methods with 3% to 10% improvement in recognition accuracy.
Diabetic cardiac fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Cardiac fibroblast autophagy plays critical roles in diabetic cardiac fibrosis, however, the ...underlying mechanism of cardiac fibroblast autophagy and diabetic cardiac fibrosis still largely unknown. The aim of the study was to investigate the mechanism of DNMT1 mediated DNA methylation alterations control cardiac fibroblast autophagy in diabetic cardiac fibrosis. We employed streptozotocin (STZ)-induced rats DCM, DCM patient and Hcy induced cardiac fibroblast autophagy. Heart tissue sections were stained with H&E, Sirius Red and Masson's trichrome stain. The expression of DNMT1, AR, Collagen genes mRNA was detected by qRT-PCR. MSP and BSP detected the methylation status of the AR promoter. The expression of DNMT1, AR, Collagen and autophagy-related proteins were detected by Western blotting, Immunofluorescence, Immunohistochemistry. Gain and loss function of AR and DNMT1 in cardiac fibroblast was analyzed. DNMT1 inhibition or knockdown elevated the expression of AR in cardiac fibroblast. Furthermore, we found that AR negatively regulation of Hcy induced cardiac fibroblast autophagy. We demonstrated that DNMT1 enhances cardiac fibroblast autophagy in diabetic cardiac fibrosis through inhibiting AR axis. In conclusion, our results provide new insight into the DNMT1 inactivation of AR axis triggers cardiac fibroblast autophagy in diabetic cardiac fibrosis.
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•DNMT1 up regulation in Hcy induced CFs and diabetic cardiac fibrosis.•AR negatively regulation of Hcy induced CFs autophagy.•DNMT1 inactivation of AR axis triggers CFs autophagy in diabetic cardiac fibrosis.
In this paper, a new adaptive hierarchical sliding mode control scheme for a 3D overhead crane system is proposed. A controller is first designed by the use of a hierarchical structure of two ...first-order sliding surfaces represented by two actuated and un-actuated subsystems in the bridge crane. Parameters of the controller are then intelligently estimated, where uncertain parameters due to disturbances in the 3D overhead crane dynamic model are proposed to be represented by radial basis function networks whose weights are derived from a Lyapunov function. The proposed approach allows the crane system to be robust under uncertainty conditions in which some uncertain and unknown parameters are highly difficult to determine. Moreover, stability of the sliding surfaces is proved to be guaranteed. Effectiveness of the proposed approach is then demonstrated by implementing the algorithm in both synthetic and real-life systems, where the results obtained by our method are highly promising.
Herein, a divergent synthesis of a variety of 2α‐ and 5α‐substituted furan derivatives from 2‐hydroxy‐1,4‐diones is reported. By using appropriate substrates and an acid catalyst, the reactions ...occurred selectively through cyclization/1,6‐conjugate addition or cyclization/Friedel–Crafts‐type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6‐conjugate addition for 5α substitution and >20 types for the Friedel–Crafts‐type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity‐oriented synthesis of α‐substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4‐hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.
Great selection! We present herein a de novo and divergent synthesis of 2α‐ and 5α‐substituted furans from 2‐hydroxy‐1,4‐diones and a variety of nucleophiles with good regio‐ and chemoselectivity, as well as a very broad substrate scope (>10 types of nucleophiles for the 5α functionalization and >20 types of nucleophiles for the 2α functionalization; see scheme). The products show good potential as antifungal agents.
Objective: To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund's adjuvant-induced arthritis rat models. Methods: We isolated and identified five ...compounds in the ethanol-soluble Solanum procumbens extract (SP) with anti-inflammatory effects, including ursolic acid, β-sitosterol, hexadecanoic acid, cis-vaccenic acid, and vanillic acid. Additionally, we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms, including paw volumes, local temperatures, withdrawal latency, and mechanical withdrawal threshold at the hind paw and white blood cell (WBC) number from complete Freund's adjuvant-induced arthritis rat models. Results: We have successfully established a complete Freund's adjuvant-induced arthritis rat model at a low dose (1 mg/mL). SP extract significantly reduced paw volumes (P<0.05), prolonged withdrawal latencies (P<0.05), decreased local temperature, and increased the mechanical withdrawal threshold (P<0.05), but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers. Conclusions: SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis, but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.
Long non coding RNA growth arrest-specific transcript 5 (LncRNA GAS5) participate in the formation of fibrosis diseases. However, the key role of LncRNA GAS5 in the development of cardiac fibrosis ...remains unclear. Accumulating evidence suggests that DNA methylation alterations play a central role in cardiac fibroblast activation. In this study, we explored MeCP2 inactivation of LncRNA GAS5 leads to down regulation of LncRNA GAS5 expression in cardiac fibrosis. Gain and loss function of LncRNA GAS5 and MeCP2 was analyzed. The expression of LncRNA GAS5 was significantly decreased in cardiac fibrosis tissues, while MeCP2 was significantly increased. Moreover, the expression of MeCP2 was increased in TGF-β1 induced cardiac fibroblasts, while the expression of LncRNA GAS5 was decreased. Down regulation of LncRNA GAS5 resulted in increasing cellular proliferation. In contrast, exogenous over expression of LncRNA GAS5 in cardiac fibroblasts inhibited cell proliferation. 5-AzadC or knockdown of MeCP2 treatment significantly restored LncRNA GAS5 expression in cardiac fibroblasts, while over expression of MeCP2 treatment significantly inhibited LncRNA GAS5 expression in cardiac fibroblasts. In summary, these results suggested that MeCP2 silencing of LncRNA GAS5 triggers cardiac fibroblasts activation in cardiac fibrosis.
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•LncRNA GAS5 controls cardiac fibroblast activation and fibrosis.•MeCP2 inactivation of LncRNA GAS5 in activated cardiac fibroblast.•MeCP2 and GAS5 regulate cardiac fibroblast activation via Smad3 axis.
In this paper, we investigate maximal subgroups of an almost subnormal subgroup
G
in a division ring
D
whose center is infinite. Among results, we prove that if
M
is such a maximal subgroup, then
M
...is abelian provided
M
is either locally finite or
FC
-group, and
D
is weakly locally finite. Also, we prove a theorem on the existence of non-cyclic free subgroups of a maximal subgroup
M
in such a
G
.
Although curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models ...is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.
This paper analyzes the optimal regulation for “Too Big to Fail” (TBTF) in a simple model. As the government cannot credibly commit to no bail-out during crises, banks have an incentive to become ...excessively large ex-ante. In this case, no single policy can fully eliminate the inefficiencies from TBTF. The optimal regulation for the first-best allocation features a capital requirement and an issuance of Contingent Convertible Bonds (CoCos) where the former addresses the moral hazard issue from government bailouts and the latter improves risk-sharing. Moreover, a combination of the capital requirement and size regulation can implement a second-best allocation where the government has to bail out the banking sector but the social cost of bail-out is internalized by the banks. In this case, the capital requirement forces banks to internalize the bailout cost while the size regulation directly discourages banks to become large.
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