PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway.

BACKGROUND: Mitochondrial dysregulation in skeletal myocytes is considered a major factor in aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target of rapamycin complex 1 (mTORC1) in aged skeletal muscles. METHODS: C2C12 myoblasts were stimulated by 50 µM 7ß-hydroxycholesterol (7ß-OHC) to observe the changes of DNA damage, mitochondrial membrane potential (Δψm), mitochondrial ROS and PGC-1α protein. The PGC-1α silence in the C2C12 cells was established by siRNA transfection. The levels of DNA damage, Δψm, mitochondrial ROS, Sestrin2 and p-S6K1/S6K1 proteins were observed after the PGC-1α silence in the C2C12 cells. Recombinant Sestrin2 treatment was used to observe the changes of DNA damage, Δψm, mitochondrial ROS and p-S6K1/S6K1 protein in the 7ß-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. Wild-type (WT) mice and muscle-specific PGC-1α conditional knockout (MKO) mice, including young and old, were used to analyse the effects of PGC-1α on muscle function and the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles. Recombinant Sestrin2 was administrated to analyse its effects on muscle function in the old WT mice and old MKO mice. RESULTS: 7ß-OHC treatment induced DNA damage, mitochondrial dysfunction and decrease of PGC-1α protein in the C2C12 cells. PGC-1α silence also induced DNA damage and mitochondrial dysfunction in the C2C12 cells. Additionally, PGC-1α silence or 7ß-OHC treatment decreased the levels of Sestrin2 and p-S6K1/S6K1 protein in the C2C12 cells. Recombinant Sestrin2 treatment significantly improved the DNA damage and mitochondrial dysfunction in the 7ß-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia and decreased the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles when compared to the WT mice. Recombinant Sestrin2 treatment improved muscle function and increased p-S6K1 levels in the old two genotypes. CONCLUSION: This research demonstrates that PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway.

Orientational Distribution Learning With Hierarchical Spatial Attention for Open Set Recognition.

Open set recognition (OSR) aims to correctly recognize the known classes and reject the unknown classes for increasing the reliability of the recognition system. The distance-based loss is often employed in deep neural networks-based OSR methods to constrain the latent representation of known classes. However, the optimization is usually conducted using the nondirectional euclidean distance in a single feature space without considering the potential impact of spatial distribution. To address this problem, we propose orientational distribution learning (ODL) with hierarchical spatial attention for OSR. In ODL, the spatial distribution of feature representation is optimized orientationally to increase the discriminability of decision boundaries for open set recognition. Then, a hierarchical spatial attention mechanism is proposed to assist ODL to capture the global distribution dependencies in the feature space based on spatial relationships. Moreover, a composite feature space is constructed to integrate the features from different layers and different mapping approaches, and it can well enrich the representation information. Finally, a decision-level fusion method is developed to combine the composite feature space and the naive feature space for producing a more comprehensive classification result. The effectiveness of ODL has been demonstrated on various benchmark datasets, and ODL achieves state-of-the-art performance.

Black corn (Zea mays L.) soluble extract showed anti-inflammatory effects and improved the intestinal barrier integrity in vivo (Gallus gallus).

Black corn (Zea mays L.) is a pigmented type of this cereal whose color of the kernels is attributed to the presence of the anthocyanins. In this study, we assessed the black corn soluble extract (BCSE) effects on the intestinal functionality, morphology, and microbiota composition using an in vivo model (Gallus gallus) by an intra-amniotic administration. The eggs were divided into four groups (n = 6-10): (1) No Injection; (2) 18 MΩ H2O/cm; (3) 5% (5 mg/mL) BCSE; (4) 15% (15 mg/mL) BCSE. The BCSE showed anti-inflammatory effects by down regulating the gene expression of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), and the transcriptional nuclear factor kappa beta (NF-κB). Further, the BCSE increased the relative abundance of E. coli and Clostridium. 5% and 15% BCSE increased the hepatic glycogen and upregulated the gene expression of sodium-glucose transport protein (SGLT1). In the morphology, 5% and 15% BCSE increased the goblet cell (GC) number on the crypt, the GC size on the villi, Paneth cell number on the crypt, and the acid GC. Further, the BCSE strengthened the epithelial physical barrier through upregulating the intestinal biomarkers AMP- activated protein kinase (AMPK) and caudal-related homeobox transcriptional factor 2 (CDX2). The overall result suggests that the BCSE promotes intestinal anti-inflammatory effects as well as enhances the intestinal barrier function.

LncRNA RP5-857K21.7 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells through the miR-508-3p/PI3K/AKT/mTOR axis.

The continuous increase in the prevalence of asthma poses a threat to human health. Despites numerous researches, the understanding of asthma development still remain elusive, hindering the development of effective treatment. Here, we explored the role of lncRNA RP5-857K21.7 (RP5-857K21.7) in the development of asthma and its potential molecular mechanism of regulation. Airway smooth muscle cells (ASMCs) were isolated and cultured after which some of the cells were induced with PDGF-BB to build an asthma cell model, and then, qRT-PCR analysis was used to measure the expression level of RP5-857K21.7 in the cell model. Result shows that the RP5-857K21.7 is significantly downregulated in PDGF-BB-induced ASMCs cells. Through CCK-8, transwell, and flow cytometry assay, we examined the functional impact of RP5-857K21.7 on the proliferation, migration, and apoptosis of the ASMCs, respectively, and found that the overexpression of RP5-857K21.7 markedly inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. Bioinformatics analysis predicted that the RP5-857K21.7 could sponge miR-508-3p and result was validated through a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR analysis. Mechanistically, RP5-857K21.7 regulates the PI3K/AKT/mTOR pathway by endogenously sponging miR-508-3p to inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. The current research suggests that the RP5-857K21.7 and its associated molecular pathway (miR-508-3p/PI3K/AKT/mTOR axis) might be a useful therapeutic target for the treatment of asthma disease.

From State-controlled to Polycentric Governance in Forest Landscape Restoration: The Case of the Ecological Forest Purchase Program in Yong'an Municipality of China.

Forest landscape restoration is emerging as an effective approach to restore degraded forests for the provision of ecosystem services and to minimize trade-offs between conservation and rural livelihoods. Policy and institutional innovations in China illustrate the governance transformation of forest landscape restoration from state-controlled to polycentric governance. Based on a case study of the Ecological Forest Purchase Program in Yong'an municipality, China's Fujian Province, this paper explores how such forest governance transformation has evolved and how it has shaped the outcomes of forest landscape restoration in terms of multi-dimensionality and actor configurations. Our analysis indicates that accommodating the participation of multiple actors and market-based instruments facilitate a smoother transition from state-centered to polycentric governance in forest landscape restoration. Governance transitions for forest landscape restoration must overcome a number of challenges including ensurance of a formal participation forum, fair participation, and a sustainable legislative and financial system to enhance long-term effectiveness.

Effects of olmesartan on endothelial progenitor cell mobilization and function in carotid atherosclerosis.

BACKGROUND: Olmesartan is a type of angiotensin II receptor inhibitor that can reduce the incidence of cardiovascular events. However, its role in the function of endothelial progenitor cells in atherosclerosis patients is still unclear. Our study aimed to explore the effects and mechanism of olmesartan on endothelial progenitor cell mobilization and function in carotid atherosclerosis. MATERIAL/METHODS: Forty carotid atherosclerosis patients were enrolled. Patients were administrated olmesartan 20 mg/day for 3 months. Flow cytometry was used for counting circulating endothelial progenitor cells; colorimetric method was used to measure the serum levels of endothelial nitric oxide synthase and nitric oxide. Cell migration, adhesion, and proliferation capacity, and related signaling pathway were also analyzed. Spearman rank correlation analysis was used to investigate the influence of olmesartan on endothelial progenitor cells and clinical characteristics (e.g., sex, age, blood pressure). RESULTS: Compared with the control group, the number of circulating endothelial progenitor cells was significantly decreased. Olmesartan can increase circulating endothelial progenitor cells number and the serum levels of eNOS and NO. Furthermore, it can improve cell migration, adhesion, and proliferation capacities. Spearman rank correlation analysis showed there is no relationship between olmesartan promotion effects on endothelial progenitor cell mobilization and the clinical characteristics (P>0.05). P-eNOS and P-Akt expression can be unregulated by RNH-6270 treatment and blocked by LY294002. CONCLUSIONS: Olmesartan can effectively promote the endothelial progenitor cells mobilization and improve their function in patients with carotid atherosclerosis, independent of basic characteristics. This process relies on the PI3K/Akt/eNOS signaling pathway.