Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in skeletal myocytes contributes to hyperglycemia in diabetes. Although glucose is known to stimulate ...insulin secretion by β cells, whether it directly engages nutrient signaling pathways in skeletal muscle to maintain systemic glucose homeostasis remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. Mechanistically, glucose triggers KATP channel-dependent calcium signaling, which promotes HDAC5 phosphorylation and nuclear exclusion, leading to Baf60c induction and insulin-independent AKT activation. This pathway is engaged by the anti-diabetic sulfonylurea drugs to exert their full glucose-lowering effects. These findings uncover an unexpected mechanism of glucose sensing in skeletal myocytes that contributes to homeostasis and therapeutic action.
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•Skeletal myocytes engage in physiological glucose sensing via the KATP channel•Glucose stimulates insulin-independent AKT activation through HDAC5/Baf60c•Muscle glucose sensing is required for postprandial glucose homeostasis•Sulfonylureas lower blood glucose in part through the Baf60c-Deptor-AKT axis
Skeletal myocytes directly sense extracellular glucose concentrations and activate a signaling pathway to drive hormone-independent AKT activation. This glucose-sensing pathway acts in concert with insulin to promote muscle glucose utilization and maintain systemic glucose homeostasis.
NAC (NAM, ATAF1,2, and CUC2) transcription factors play an important role in the responses of plants to various environmental stresses. To investigate the function of SlNAC1, which was found to be a ...member of the ATAF subfamily in tomato (Solanum lycopersicum L.) plants under heat stress conditions, transgenic tomato plants were generated using an antisense technology. After a treatment at 40 °C for 48 h, in comparison with wild-type (WT) plants, the transgenic plants were severely wilted and exhibited a lower net photosynthetic rate and a maximal photochemical efficiency of photosystem II. Moreover, the transgenic plants displayed a higher ion leakage and malondialdehyde content and a lower proline content. The content of reactive oxygen species (superoxide anion radicals and hydrogen peroxide) were higher, and activities of ascorbate peroxidase and superoxide dismutase lower in the transgenic plants than in the WT plants. The transgenic plants also exhibited a lower accumulation of the transcripts of some heat shock protein genes (Hsp70, Hsp90, sHsp17.4, and sHsp17.6). All of these results suggest that the suppression of SlNAC1 could obviously reduce heat resistance in the tomato plants, and this indicates that SlNAC1 played an important role in the thermal tolerance of the tomato plants.
Abstract
This paper focuses on the modification technologies of Poly (p-phenylene benzobisoxazole) (PBO) fibers and their research progress. It is found that the modification of compression ...resistance, surface inertia, and ultraviolet (UV) aging resistance of PBO fibers can greatly promote the wide application of PBO fibers in advanced composites. More researches are yet to be done on the new modification technologies of PBO fibers in compression resistance, and the future development direction of surface modification and UV aging resistance modification is towards realizing non-destructive modification and large-scale and industrialized online treatment.
The aim of this study was to determine the effect of calcium propionate (CaP) on rumen microbiota, fermentation indicators, and weight gain in calves both pre- and postweaning. Twenty-four newborn ...calves were randomly divided into 4 groups (2 × 2 factorial treatment arrangement): either pre- (90 d) or postweaning (160 d), and either without or with dietary CaP supplementation (5% dry matter). The CaP supplementation increased the body weight and rumen weight of the calves and lowered NH3-N concentration in the rumen. Microbiota composition was characterized by sequencing the amplicons of the bacterial and archaeal 16S rRNA genes. The CaP supplementation decreased the relative abundance of the phylum Bacteroidetes but tended to increase that of Proteobacteria. In addition, CaP supplementation decreased the diversity of bacteria and archaea in the rumen compared with the calves fed the control diet. Linear discriminant analysis of the rumen microbiota revealed that Succinivibrionaceae and Methanobrevibacter were enriched in the CaP group postweaning. A correlation was also present between the acetate to propionate ratio and the species that acted as co-occurrence network hubs, including Succiniclasticum, Treponema, and Megasphaera. In conclusion, CaP supplementation can improve body weight gain and rumen growth and alter the ruminal microbiota in calves both pre- and postweaning.
The metal hydride reactors are widely used in many industrial applications, for example, hydrogen storage, heat pump, thermal compression, gas separation, etc. The performance of the reactor is ...greatly affected by its design, which deserves careful study. Given the complicated nature of the hydride formation/decomposition processes, a series of technical issues are involved in the design of metal hydride reactors, such as primary configuration, thermal management, hydrogen transfer and mechanistic strength. These issues should be well addressed to fulfil the requirement of specific application. In this paper, the representative achievements with regards to the design issues so far were reviewed in detail, and some comments were made accordingly. It was concluded that an optimized reactor design comes from integrated considerations of numerous factors, particularly requirements for the applications and characteristics of the metal hydride system. The analytic hierarchy process was recommended for use in the selection of the optimum reactor scheme.
•Curve channel with periodical wave structure is proposed to enhance heat transfer.•Secondary flow in curve-wave channel generates more vortices disturbing main flow stream.•Thermal boundary layer in ...curve-wave channel redevelops periodically along main flow direction.•Heat transfer enhanced by curve-wave channel outweighs its pressure penalty.•The optimum wave amplitude can be obtained by evaluating the dimensionless performance factor.
Flow and heat transfer in curve channel have been studied extensively due to the presence of the secondary flow induced by the centrifugal force. However, for the curved channel with small curvature, weakened centrifugal force reduces the intensity of secondary flow and heat transfer enhancement is attenuated accordingly. For sake of maintaining high heat transfer efficiency in curve channel with a wide range of curvature, periodical wave structure was introduced into the smooth-curve channel by this study. A three-dimensional model of the curve-wave structure was established and numerical simulation was carried out to explore the flow characteristics and heat transfer performance in the proposed channel. In addition, the effects of the wave amplitude on the channel performance were analyzed. The results showed that the heat transfer of smooth-curve channel can be enhanced remarkably by applying wave structure on the channel wall, and the overall performance factor indicates that the heat transfer argumentation outweighs the pressure loss penalty. It was also found that the heat transfer in the curve-wave channel can be further enhanced by increasing wave amplitude. The most effective heat transfer enhancement can be achieved based on the evaluation of the overall performance factor.
Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged ...betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options.
A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy.
A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19
MIF
epithelial cells and via epithelial-stromal crosstalk.
Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
In the present study, calcium propionate (CaP) was used as feed additive in the diet of calves to investigate their effects on rumen fermentation and the development of rumen epithelium in calves. To ...elucidate the mechanism in which CaP improves development of calf rumen epithelium via stimulating the messenger RNA (mRNA) expression of G protein-coupled receptors, a total of 54 male Jersey calves (age=7±1 days, BW=23.1±1.2 kg) were randomly divided into three treatment groups: control without CaP supplementation (Con), 5% CaP supplementation (5% CaP) and 10% CaP supplementation (10% CaP). The experiment lasted 160 days and was divided into three feeding stages: Stage 1 (days 0 to 30), Stage 2 (days 31 to 90) and Stage 3 (days 91 to 160). Calcium propionate supplementation percentages were calculated on a dry matter basis. In total, six calves from each group were randomly selected and slaughtered on days 30, 90 and 160 at the conclusion of each experimental feeding stage. Rumen fermentation was improved with increasing concentration of CaP supplementation in calves through the first 30 days (Stage 1). No effects of CaP supplementation were observed on rumen fermentation in calves during Stage 2 (days 31 to 90). Supplementation with 5% CaP increased propionate concentration, but not acetate and butyrate in calves during Stage 3 (days 91 to 160). The rumen papillae length of calves in the 5% CaP supplementation group was greater than that of Con groups in calves after 160 days feeding. The mRNA expression of G protein-coupled receptor 41 (GPR41) and GPR43 supplemented with 5% CaP were greater than the control group and 10% CaP group in feeding 160 days calves. 5% CaP supplementation increased the mRNA expression of cyclin D1, whereas did not increase the mRNA expression of cyclin-dependent kinase 4 compared with the control group in feeding 160-day calves. These results indicate that propionate may act as a signaling molecule to improve rumen epithelium development through stimulating mRNA expression of GPR41 and GPR43.
Propionibacterium acnes plays a major role in acne vulgaris. In the pre‐experiment, the growth of P. acnes was inhibited effectively using surfactin; however, the antibacterial mechanism has not been ...described. Therefore, the aim of this study was to evaluate antibacterial activity and analyse the mechanism of surfactin against P. acnes. Minimum inhibitory concentration, time‐killing kinetics and scanning electron microscopy were used to evaluate the activity of surfactin against P. acnes, which showed that 128 μg ml−1 effectively inhibited growth. Cell wall permeability was evaluated by detecting the extracellular alkaline phosphatase activity, which increased to 1·83‐ and 2·32‐fold after incubating with 128 and 256 μg ml−1 of surfactin for 10 h, respectively. Propidium iodide fluorescence, leakage of nucleic acid, protein, K+, and Ca2+, membrane potential and the leakage of calcein from small unilamellar vesicles all increased after incubation with surfactin, indicating that its strong biological activities act mainly by altering membrane integrity. In a mouse model of acne, surfactin significantly reduced P. acnes–induced epidermal swelling and erythema. These results indicate that surfactin effectively inhibited the growth of P. acnes by destroying the cell wall and membrane, and is a potential candidate for acne treatment.
Significance and Impact of the Study: Surfactin has a wide range of targets, thus drug resistance development is difficult. This study clarified the antibacterial mechanism of surfactin against Propionibacterium acnes, which would benefit the development of acne cosmetics and cosmeceuticals, and provide a potential method for producing acne‐treating natural ingredients.
•A Zr/ZrC modified layer was formed on AISI 440B stainless steel using plasma surface Zr-alloying.•The thickness of the modified layer increases with alloying temperature and time.•Formation ...mechanism of the modified layer is dependent on the mutual diffusion of Zr and substrate elements.•The modified surface shows an improved wear resistance.
The surface Zr/ZrC gradient alloying layer was prepared by double glow plasma surface alloying technique to increase the surface hardness and wear resistance of AISI 440B stainless steel. The microstructure of the Zr/ZrC alloying layer formed at different alloying temperatures and times as well as its formation mechanism were discussed by using scanning electron microscopy, glow discharge optical emission spectrum, X-ray diffraction and X-ray photoelectron spectroscopy. The adhesive strength, hardness and tribological property of the Zr/ZrC alloying layer were also evaluated in the paper. The alloying surface consists of the Zr-top layer and ZrC-subsurface layer which adheres strongly to the AISI 440B steel substrate. The thickness of the Zr/ZrC alloying layer increases gradually from 16μm to 23μm with alloying temperature elevated from 900°C to 1000°C. With alloying time from 0.5h to 4h, the alloyed depth increases from 3μm to 30μm, and the ZrC-rich alloyed thickness vs time is basically parabola at temperature of 1000°C. Both the hardness and wear resistance of the Zr/ZrC alloying layer obviously increase compared with untreated AISI 440B steel.
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