Search

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the influence of modification of ceramic fillers on the dielectric properties of polymer-based composites, TiO 2 and core-shell structured TiO 2 @HfO 2 nanowires were synthesized, and investigated in this study. TiO 2 nanowires/polyvinylidene fluoride (PVDF) and TiO 2 @HfO 2 nanowires/PVDF nanocomposites were prepared using the solution casting method. The experimental results showed that the TiO 2 @HfO 2 nanowires/PVDF composites had improved dielectric properties compared with that of the TiO 2 nanowires/PVDF composites. Owing to the enhanced interfacial polarisation by the multilevel interface, the composites with 10 wt % TiO 2 @HfO 2 nanowires achieved the highest permittivity of 12.56 at 1 kHz, which was enhanced by ∼72% compared to the PVDF matrix. The electric field was evenly distributed by building the fillers with a gradient dielectric constant. The characteristic breakdown strength of the composite with 5 wt % TiO 2 @HfO 2 reached 377.76 kV/mm, compared with that of 334.37 kV/mm for the composite with 5 wt % TiO 2 nanowires. This study initiated a novel strategy for preparing dielectrics with high dielectric constant and improved breakdown strength. [ABSTRACT FROM AUTHOR]

To achieve greener healthcare with the goal of net-zero carbon, it is urgent to motivate healthcare-employees to voluntarily participate in green behavior. Our focus is on examining a novel predictor of voluntary green behavior (VGB): socially responsible human resource management (SRHRM). Drawing on social information processing theory, a theoretical model was built to linking SRHRM and VGB. Based on the healthcare sector, we examined the mediating effect of green passion and the moderating effect of CSR attributions in the above mediation. We employed two studies: Study 1, which includes two experiments to examine the boundary of CSR attributions (H1 and H4), and Study 2, which empirically tested the mediated moderation model (H1–H4). We found that (a) SRHRM was positively associated with VGB; (b) green passion mediates the relation between SRHRM and VGB; and (c) CSR attributions moderate the association between SRHRM and green passion and influence the indirect effect of SRHRM on VGB (via green passion). We further elaborate on the implications, acknowledge limitations, and propose directions for future research. [ABSTRACT FROM AUTHOR]

Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. In this study, we established a murine model of high-fat diet-induced obesity (DIO) and introduced adeno-associated virus delivery of short hairpin RNA to knock down Atg7 (sh Atg7) into the gastrocnemius muscle. We then examined the expressions of Atg7 and myoprotein degradation markers in the gastrocnemius tissues of obese patients and mice using immunofluorescence and western blotting techniques. To further investigate the effects of Atg7, we assessed skeletal muscle cell diameter and the myoprotein degradation pathway in C2C12 and HSkMC cells in the presence or absence of Atg7. Immunofluorescence staining for MyHC and western blotting were utilized for this purpose. To understand the transcriptional regulation of Atg7 in response to myoprotein degradation, we conducted luciferase reporter assays and chromatin immunoprecipitation experiments to examine whether FoxO3a enhances the transcription of Atg7. Moreover, we explored the role of Akt in Atg7-mediated regulation and its relevance to obesity-induced muscle mass decline. This was accomplished by Akt knockdown, treatment with MK2206, and GST pulldown assays to assess the interaction between Atg7 and Akt. After 20 weeks of being on a high-fat diet, obesity was induced, leading to a significant decrease in the gastrocnemius muscle area and a decline in muscle performance. This was accompanied by a notable increase in Atg7 protein expression (p < 0.01). Similarly, in gastrocnemius tissues of obese patients when compared to nonobese individuals, there was a significant increase in both Atg7 (p < 0.01) and TRIM63 (p < 0.01) levels. When palmitic acid was administered to C2C12 cells, it resulted in increased Atg7 (p < 0.01), LC3Ⅱ/Ⅰ (p < 0.01), and p62 levels (p < 0.01). Additionally, it promoted FoxO3a-mediated transcription of Atg7. The knockdown of Atg7 in the gastrocnemius partially reversed DIO-induced muscle mass decline. Furthermore, when Atg7 was knocked down in C2C12 and HSkMC cells, it mitigated palmitic acid-induced insulin resistance, increased the p-Akt/Akt ratio (p < 0.01), and reduced TRIM63 (p < 0.01). Muscular atrophy mediated by Atg7 was reversed by genetic knockdown of Akt and treatment with the p-Akt inhibitor MK2206. Palmitic acid administration increased the binding between Atg7 and Akt (p < 0.01) while weakening the binding of PDK1 (p < 0.01) and PDK2 (p < 0.01) to Akt. GST pulldown assays demonstrated that Atg7 directly interacted with the C-terminal domain of Akt. The consumption of a high-fat diet, along with lipid-induced effects, led to the inhibition of Akt signaling, which, in turn, promoted FoxO3a-mediated transcription, increasing Atg7 levels in muscle cells. The excess Atg7 inhibited the phosphorylation of Akt, leading to a cyclic activation of FoxO3a and exacerbating the decline in muscle mass regulated by obesity. Consequently, Atg7 serves as a regulatory point in determining the decline in muscle mass induced by obesity. [Display omitted] • Atg7 is a key regulatory node in promoting obesity-induced muscular mass decline. • Lipid-induced inhibition of Akt signaling promotes FoxO3a-mediated transcription of Atg7. • Atg7 directly interacts with the C-terminal domain of Akt, causing cyclic activation of FoxO3a. • Dysfunction of the Akt/FoxO3a/Atg7 regulatory loop exacerbates the obesity-triggered muscular mass decline. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a widely used agricultural herbicide, and its accumulation in soil and water can cause various environmental health problems. ATR has neurotoxic effects on dopaminergic neurons, which can lead to a Parkinson's disease (PD)-like syndrome. Epigenetics regulates gene expression dynamically through DNA methylation, histone post-translational modification, microRNA (miRNA) interaction, and RNA methylation. MicroRNA (miRNA), representing one of the primary epigenetic mechanisms responsible for regulating gene expression, plays a crucial role in maintaining normal cellular function, while dysregulation of miRNA expression has been observed in PD. This study aims to investigate the regulatory mechanisms of miRNA in ATR exposure. The results show that ATR-exposure significantly upregulates the expression level of miR-217-5p. Both miR-217-5p overexpression and ATR exposure is able to trigger the autophagy process and apoptosis. Conversely, inhibiting the expression of miR-217-5p can reverse the levels of ATR-induced autophagy and apoptosis. Moreover, ATR causes damage to dopaminergic neurons, as indicated by the altered expression of tyrosine hydroxylase and α-synuclein. Taken together, these results suggest that ATR-induced autophagy can accelerate the progression of neurodegenerative diseases and that miR-217-5p is probably an important target involved in ATR-induced dopaminergic damage, shedding important light on the development of a novel strategy for treating neurodegenerative diseases. [Display omitted] • ATR can increase α-syn expression and cause the dopaminergic neurons damage. • MiR-217-5p could be a crucial target involved in the mechanism of ATR-induced damage to dopaminergic neurons. • MiR-217-5p can increase apoptosis by regulating mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Guizhi Shaoyao Zhimu decoction, a traditional Chinese medicine formula used empirically for the treatment of rheumatoid arthritis (RA), has been shown to alleviate bone destruction in rats with collagen-induced arthritis (CIA). The aim of this study is to characterize the effects of Guizhi Shaoyao Zhimu granules (GSZGs) on bone destruction in RA and the underlying mechanism. A CIA arthritis model using DBA/1 mice. The animals were divided into a normal group; CIA model group; low, medium, and high-dose GSZG groups (3, 6, and 9 g/kg/day); and a methotrexate group (1.14 mg/kg/w). In vitro , a cytokine induced osteoclastogenesis model was established. After 28 days of treatment, the paw volume was measured, bone destruction was examined by micro-CT, and the generation of osteoclasts in bone tissue was evaluated via tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, the inhibitory effect and underlying mechanism of action of GSZG on RANKL-induced osteoclastogenesis were investigated in vitro. The in vivo analyses demonstrated that the paw volume and degree of bone erosion of mice in the medium- and high-dose GSZG groups were significantly decreased compared to the CIA model group. In addition, GSZG treatment suppressed the excessive generation of osteoclasts in the bone tissue of CIA mice. In vitro , GSZG inhibited RANKL-induced osteoclastogenesis and osteoclast-mediated bone resorption. Specifically, it only inhibited the generation of osteoclast precursors (OCPs); it had no significant effect on the fusion of OCPs or maturation of osteoclasts. Finally, we showed that the inhibitory effect of GSZG on osteoclastogenesis was related to the promotion of PTEN-induced kinase protein 1 (PINK1)/Parkin pathway-mediated mitophagy of osteoclast precursors, which was verified using a PINK1 knockdown small interfering RNA in OCPs. These findings indicate that GSZG is a candidate for the treatment of bone destruction in RA and provide a more detailed elucidation of the mechanism of GSZG anti-RA bone erosion, i.e. , inhibition of the ROS/NF-κB axis through the PINK1/Parkin-mediated mitochondrial autophagic pathway to inhibit osteoclast precursor production, compared to the published literature. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract The determination of micromechanical properties of additive manufactured ceramics is essential to address reliability issues in engineering application. Alumina ceramics were fabricated by stereolithography-based additive manufacturing with different layer thickness. The microstructure and micro-mechanical properties were investigated systematically, by means of scanning electron microscopy, nanoindentation and micro-scratch tests. The characteristics of alumina ceramic green bodies mainly depended on the layer thickness, while scratch morphologies was discussed in terms of the integrity and homogeneity of microstructure. The results indicated that scratch damage evolution was independent of layer thickness since no correlation between cracking and layering characteristic was verified under all scratch tests. [ABSTRACT FROM AUTHOR]

Abstract This paper provides a comprehensive understanding of the influence mechanism of short fiber toughening on low-velocity impact resistance of carbon fiber reinforced polymer composite laminates (CFRPs). Three kinds of layup laminates with and without short Kevlar-fiber toughening were designed and experimental tests were conducted using a drop-weight impact machine. After the low-velocity impact test, ultrasonic C-scan and industrial computed tomography (ICT) were utilized to comprehensively reveal the internal damage, including damage area and damage distribution. Based on the energy absorption and the impact dynamic responses, mechanical behaviors of CFRPs were analyzed in detail. Furthermore, the residual compression strength and failure strain of CFRPs with and without short Kevlar-fiber toughening were tested. It was observed that damage resistance of toughened laminates at lower impact energy did not show obvious advantages, but the compression-after-impact (CAI) strengths and the failure strain values improved under all energy levels with short Kevlar-fiber toughening. Three-dimensional distribution of internal damage and electron microscope analysis, together with fracture toughness analysis, were employed to explain the experimental findings and relevant mechanisms. [ABSTRACT FROM AUTHOR]