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Objective To investigate the effects of dexmedetomidine (Dex) on osteoporosis (OP) rats and possible mechanisms. Methods The rats were divided into sham operation group, osteoporosis model group (OP, replicating the OP rat model with bilateral ovariectomies), Dex-L, M, and H (Dex low, medium, and high dose treatments) groups and Dex-H+XAV-939 group (Wnt/β-catenin pathway inhibitor). Micro-CT was applied to measure bone mineral density (BMD) and bone microstructure of rat femurs. The three-point bending experiment was applied to analyze the biomechanics of the femur (maximum load, fracture deflection, elastic modulus). HE staining was applied to observe pathological changes in the femur of rats. ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP), typeⅠ procollagen amino-terminal peptide (PINP) and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ). The expression of Runx2 and Wnt3a was examined by Immunohistochemistry. Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue. Results Compared to the Sham group, the bone volume and number of trabeculae in OP group were obviously reduced, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased, CTX-Ⅰ increased (P＜0.05). Compared to the OP group, the bone trabecular structure in the Dex-L, M, and H groups was restored, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression all increased but CTX-Ⅰ decreased (P＜0.05). Compared to the Dex-H group, the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage. The maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased while CTX-Ⅰ increased (P＜0.05). Conclusions Dex may antagonize OP effects by improving bone density, biomechanical properties and microstructure. The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

Vaccinium oldhamii Miquel 1866 is a deciduous shrub native to Northeast Asia, including Korea, China, and Japan. Its polyphenol-rich edible berries may aid in managing chronic diseases. Despite its importance, the mitogenome of this species remains understudied. This study assembled the complete mitogenome, consisting of 626,941 bp with 45.34% GC content, using NOVOPlasty and Illumina sequencing. The genome includes 38 protein-coding genes, 24 tRNA genes, and three rRNA genes. Phylogenetic analysis revealed a close relationship with V. macrocarpon. This mitogenome provides a valuable resource for phylogenomic studies and insights into evolutionary relationships within the Vaccinium genus and the Ericales order. Vaccinium oldhamii Miquel 1866 is a deciduous shrub in the Ericales and the Ericaceae and is native to Northeast Asia including Korea, China, and Japan. Particular emphasis has been placed on the edible berries of Vaccinium species and their use as dietary supplements. Specifically, the edible berries of V. oldhamii contain high levels of polyphenols, which may aid in preventing and managing chronic diseases. However, the mitogenome sequence of this species, a valuable resource for studying evolutionary relationships and genetic diversity within the Vaccinium genus, has not been thoroughly investigated. In this study, the complete mitochondrial genome sequence of V. oldhamii was assembled into 626,941 bp circular nucleotides with a GC content of 45.34% using NOVOPlasty and Illumina sequencing data. The comprehensive annotation for mitogenome of V. oldhamii revealed that the mitogenome comprises 38 known protein-coding genes, 24 tRNA genes, and three rRNA genes. Phylogenetic analysis using ML method showed that this species is closely related to the V. macrocarpon. This newly sequenced mitochondrial genome offers a valuable resource for phylogenomic analysis and will enhance our understanding of evolutionary relationships within the Ericales order and/or the Vaccinium genus.

This study examined changes in the degree of hydrolysis, peptide yield, digestibility, and hydrolyzed amino acid content during the simulated gastrointestinal digestion of Antarctic krill protein. Furthermore, the in vitro proosteogenic activity of different concentrations of the lyophilized residue from the supernatant of the digestion product at the optimal digestion time was evaluated. The results showed that the hydrolysis degree, peptide yield, digestibility, and hydrolyzed amino acid content in the supernatant from Antarctic krill protein digestion increased significantly with digestion time, reaching an equilibrium after 120 min of intestinal digestion, with a hydrolysis degree of 42.67%, a peptide yield of 35.30% and a digestibility of 82.21%. The supernatants at all digestion time points enhanced the osteogenic activity of mouse MC3T3-E1 osteoblasts, the one obtained after 120 min of intestinal digestion being the most effective. Living/dead cell staining, alkaline phosphatase (ALP) activity assay and alizarin red staining confirmed that the supernatant from intestinal digestion for 120 min had good cellular compatibility, promoted osteoblast differentiation and mineralization and consequently regulated its osteogenic activity by enhancing ALP activity and intracellular calcium deposition. The results of this study provide a theoretical basis for the high-value application of Antarctic krill protein.

Despite increasing demand in distance education, relatively little is known about the demographic and socioeconomic characteristics as well as basic skill levels of adult distance education participants at the national level in the US. This study analyzed the US data from the 2012/2014 and 2017 Program for International Assessment of Adult Competencies (PIAAC) to identify baseline determinants of nonformal (i.e., not for a formal credential or degree) distance education among adults aged between 25 and 65 years old. Results showed that higher educational attainment, employment, literacy skills, and digital problem-solving skills were positively associated with nonformal distance education participation. As recent distance education is provided predominantly through the internet and digital device, digital skills may be of particular concern. These identified determinants should be reflected in policy interventions to close education gaps. Additionally, the findings of this study are useful for future research that focuses on psychological and behavioral factors.

Abstract Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Background and aimsThe sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC.Approach and resultsTissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99).ConclusionHCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.