HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis.

Ulcerative colitis (UC) has been identified as a severe inflammatory disease with significantly increased incidence across the world. The detailed role and mechanism of HOXD10 in UC remain unclear. In present study, we found that HOXD10 was lowly expressed in UC samples and was notably decreased by dextran sulfate sodium (DSS) administration. Overexpression of HOXD10 dramatically ameliorated DSS-induced UC symptoms, including the loss of weight, increased disease activity index values, and the shortened colon length. Additionally, terminal-deoxynucleoitidyl transferase mediated nick end labeling and immunohistochemistry staining assays showed that HOXD10 overexpression suppressed cell apoptosis and facilitated proliferation of colon tissues after DSS treatment. Moreover, HOXD10 overexpression obviously suppressed DSS-triggered inflammatory response by decreasing the expression level of TNF-α, IL-6, and IL-1ß. Furthermore, overexpression of HOXD10 effectively restored the intestinal permeability, thereby alleviating DSS-induced intestinal barrier dysfunction. Mechanistic study demonstrated that HOXD10 significantly reduced the activities of Rho/ROCK/MMPs axis in colon tissues of mice with UC. In conclusion, this study revealed that HOXD10 might effectively improve DSS-induced UC symptoms by suppressing the activation of Rho/ROCK/MMPs pathway.

Partial skeletal muscle-specific Drp1 knockout enhances insulin sensitivity in diet-induced obese mice, but not in lean mice.

OBJECTIVE: Dynamin-related protein 1 (Drp1) is the key regulator of mitochondrial fission. We and others have reported a strong correlation between enhanced Drp1 activity and impaired skeletal muscle insulin sensitivity. This study aimed to determine whether Drp1 directly regulates skeletal muscle insulin sensitivity and whole-body glucose homeostasis. METHODS: We employed tamoxifen-inducible skeletal muscle-specific heterozygous Drp1 knockout mice (mDrp1+/-). Male mDrp1+/- and wildtype (WT) mice were fed with either a high-fat diet (HFD) or low-fat diet (LFD) for four weeks, followed by tamoxifen injections for five consecutive days, and remained on their respective diet for another four weeks. In addition, we used primary human skeletal muscle cells (HSkMC) from lean, insulin-sensitive, and severely obese, insulin-resistant humans and transfected the cells with either a Drp1 shRNA (shDrp1) or scramble shRNA construct. Skeletal muscle and whole-body insulin sensitivity, skeletal muscle insulin signaling, mitochondrial network morphology, respiration, and H2O2 production were measured. RESULTS: Partial deletion of the Drp1 gene in skeletal muscle led to improved whole-body glucose tolerance and insulin sensitivity (P < 0.05) in diet-induced obese, insulin-resistant mice but not in lean mice. Analyses of mitochondrial structure and function revealed that the partial deletion of the Drp1 gene restored mitochondrial dynamics, improved mitochondrial morphology, and reduced mitochondrial Complex I- and II-derived H2O2 (P < 0.05) under the condition of diet-induced obesity. In addition, partial deletion of Drp1 in skeletal muscle resulted in elevated circulating FGF21 (P < 0.05) and in a trend towards increase of FGF21 expression in skeletal muscle tissue (P = 0.095). In primary myotubes derived from severely obese, insulin-resistant humans, ShRNA-induced-knockdown of Drp1 resulted in enhanced insulin signaling, insulin-stimulated glucose uptake and reduced cellular reactive oxygen species (ROS) content compared to the shScramble-treated myotubes from the same donors (P < 0.05). CONCLUSION: These data demonstrate that partial loss of skeletal muscle-specific Drp1 expression is sufficient to improve whole-body glucose homeostasis and insulin sensitivity under obese, insulin-resistant conditions, which may be, at least in part, due to reduced mitochondrial H2O2 production. In addition, our findings revealed divergent effects of Drp1 on whole-body metabolism under lean healthy or obese insulin-resistant conditions in mice.

Effectiveness of a combined problem-based learning and flipped classroom teaching method in ophthalmic clinical skill training.

BACKGROUND: Previous studies have primarily implemented problem-based learning (PBL) or flipped classroom (FC) teaching models in different majors; however, research on the combined PBL-FC teaching method in clinical medicine is scarce. Therefore, we investigated the combined PBL-FC teaching method in teaching ocular trauma on students' competencies. METHOD: About 75 ophthalmology postgraduates were randomly divided into PBL-FC and traditional teaching groups. Students completed pre-and post-class theoretical examinations, skills evaluation, learning ability scales, and feedback questionnaires. RESULTS: Both groups showed significantly higher theoretical scores and improved learning ability. Feedback questionnaire scores of the PBL-FC group's postgraduates without clinical experience were significantly higher than the traditional group's for some items; there was no difference between groups in postgraduates with clinical experience. PBL-FC group's pre-class preparation time was significantly longer than the traditional group's, but the post-class review time was significantly shorter. PBL-FC group's post-class theoretical performance was significantly higher than the traditional group's. There was no statistical difference between the groups regarding skill operation. Among postgraduates without clinical experience, the PBL-FC group's skill operation performance was significantly higher than the traditional group's; for postgraduates with clinical experience, the traditional group's skill operation performance was significantly higher than the PBL-FC group's. CONCLUSIONS: PBL-FC teaching is better for students without clinical experience or knowledge of ophthalmic diseases. Meanwhile, traditional teaching is a good choice for students with clinical experience who need more relevant knowledge.

The Analysis of the Innovation Consciousness of College Student Entrepreneurs Under the Teaching Concept of Chinese Excellent Traditional Culture.

The purpose of this study was to analyze the current situation of the entrepreneurial consciousness of college student entrepreneurs and to explore the role of innovative and entrepreneurial talents in social and economic development. Based on the teaching concept of Chinese excellent traditional culture, first, the relevant theories of innovation and entrepreneurship, as well as the characteristics of entrepreneurial talents in colleges and entrepreneurs, are analyzed and elaborated; moreover, the definition of college student entrepreneur is explained; then, from the perspective of entrepreneurial teaching management, entrepreneurial education, and place support, the questionnaire method is selected to show the understanding of the entrepreneurship of college students; finally, based on the Cobb-Douglas function, the model before and after the introduction of innovative and entrepreneurial talents is tested and analyzed. Investigation and analysis suggest that most college students have entrepreneurial intention, and 61.5% of them choose to start their own business after having working experience; the relative freedom of time and space is the main factor to attract college students to start their own businesses, accounting for 42.3%; 69.3% of college students think that capital is a restricting factor for entrepreneurship, while 76.2% think that lack of experience is a major restricting factor for entrepreneurship; college students have a certain demand for entrepreneurship training and guidance from the school, especially in the setting of entrepreneurship incubation park and resource pool; the characteristics of entrepreneurship, professional skills, and interpersonal resources are more crucial for college students; most college students have a positive cognition of the excellent traditional Chinese teaching concepts; the analysis based on the Cobb-Douglas function reveals that the introduction of innovative and entrepreneurial talents can promote economic development. This exploration has a positive effect on the cultivation of awareness of college students of entrepreneurship and innovation, as well as the relationship discussion between the introduction of innovative and entrepreneurial talents and social economy.

Comparative Genomics Revealing Insights into Niche Separation of the Genus Methylophilus.

The genus Methylophilus uses methanol as a carbon and energy source, which is widely distributed in terrestrial, freshwater and marine ecosystems. Here, three strains (13, 14 and QUAN) related to the genus Methylophilus, were newly isolated from Lake Fuxian sediments. The draft genomes of strains 13, 14 and QUAN were 3.11 Mb, 3.02 Mb, 3.15 Mb with a G+C content of 51.13, 50.48 and 50.33%, respectively. ANI values between strains 13 and 14, 13 and QUAN, and 14 and QUAN were 81.09, 81.06 and 91.46%, respectively. Pan-genome and core-genome included 3994 and 1559 genes across 18 Methylophilus genomes, respectively. Phylogenetic analysis based on 1035 single-copy genes and 16S rRNA genes revealed two clades, one containing strains isolated from aquatic and the other from the leaf surface. Twenty-three aquatic-specific genes, such as 2OG/Fe(II) oxygenase and diguanylate cyclase, reflected the strategy to survive in oxygen-limited water and sediment. Accordingly, 159 genes were identified specific to leaf association. Besides niche separation, Methylophilus could utilize the combination of ANRA and DNRA to convert nitrate to ammonia and reduce sulfate to sulfur according to the complete sulfur metabolic pathway. Genes encoding the cytochrome c protein and riboflavin were detected in Methylophilus genomes, which directly or indirectly participate in electron transfer.

Orthokeratology and Low-Intensity Laser Therapy for Slowing the Progression of Myopia in Children.

Orthokeratology (OK) is widely used to slow the progression of myopia. Low-level laser therapy (LLLT) provides sufficient low energy to change the cellular function. This research is aimed at verifying the hypothesis that LLLT treatment could control myopia progression and comparing the abilities of OK lenses and LLLT to control the refractive error of myopia. Eighty-one children (81 eyes) who wore OK lenses, 74 children (74 eyes) who underwent LLLT treatment, and 74 children (74 eyes) who wore single-vision distance spectacles for 6 months were included. Changes in axial length (AL) were 0.23 ± 0.06 mm for children wearing spectacles, 0.06 ± 0.15 mm for children wearing OK lens, and -0.06 ± 0.15 mm for children treated with LLLT for 6 months. Changes in subfoveal choroidal thickness (SFChT) observed at the 6-month examination were -16.84 ± 7.85 µm, 14.98 ± 22.50 µm, and 35.30 ± 31.75 µm for the control group, OK group, and LLLT group, respectively. Increases in AL at 1 month and 6 months were significantly associated with age at LLLT treatment. Changes in AL were significantly correlated with the baseline spherical equivalent refraction (SER) and baseline AL in the OK and LLLT groups. Increases in SFChT at 1 month and 6 months were positively associated with age at enrolment for children wearing OK lens. At 6 months, axial elongation had decelerated in OK lens-wearers and LLLT-treated children. Slightly better myopia control was observed with LLLT treatment than with overnight OK lens-wearing. Evaluations of age, SER, and AL can enhance screening for high-risk myopia, improve the myopia prognosis, and help determine suitable control methods yielding the most benefits.

Subfoveal Choroidal Thickness in Myopia: An OCT-Based Study in Young Chinese Patients.

Myopia is a common cause of visual impairment worldwide. Choroidal thickness (ChT) reflects the characteristic changes in myopic children and may be used as an important index of myopia. The purpose of this study was to investigate ChT and its distribution across the posterior pole in young myopic Chinese patients using enhanced depth imaging optical coherence tomography (EDI-OCT) and to explore the factors associated with it. A total of 402 myopic Chinese patients aged 6-16 years who underwent complete ophthalmic examinations, including those for axial length, cycloplegic refraction, and intraocular pressure, were examined with EDI-OCT. The mean subfoveal ChT was 303.08 ± 76.87 µm and displayed large variations at different positions (p < 0.05). The thickest sector was located 3 mm temporally from the fovea. Multivariate regression analysis showed a significant negative correlation of the subfoveal ChT values with axial length (AL), whereas the ChT was moderately influenced by the patient's sex. AL accounted for 7.9% of the ChT variance, whereas sex explained 9.6% of the ChT variance. In the population aged 11 years and older, AL accounted for 13.1% of the ChT variance. However, in those younger than 11 years, age was the only significant explanatory factor accounting for 5.2% of the ChT variance. In conclusion, we found a significant decrease in ChT with age in myopic children younger than 11 years. The negative association between age and ChT in children aged 11 years and older may be offset by the choroidal thickening mediated by pubertal growth spurts. The positive correlation between ChT and spherical equivalent in myopic adolescents aged 11 years and older suggests that the protective effect of lens thinning against rapid axial elongation disappears with age. Axial elongation becomes the dominant determinant of ChT in this age group.

Smad7 alleviates glomerular mesangial cell proliferation via the ROS-NF-κB pathway.

OBJECTIVE: The aim of this study was to demonstrate that altered gene expression of Smad7regulated NF-κB expression and ROS production on Ang II (Angiotensin II)-induced rat glomerular mesangial cell (GMC) proliferation. METHODS: pAdTrack-CMV-Smad7 was transduced into rat GMC by adeno-transduction using an ADV (adenovirus)-mediated vector in vivo. Diphenylene iodonium chloride (DPI) pre-treated GMC, and blocked ROS generation as determined by DCFH-DA method. Altered expressions of IκBα and p65 were monitored by Western blot analysis and immunofluorescence. GMC proliferation was tested by the Cell Counting Kit-8 assay. Apoptosis of GMC was detected by flow cytometric analysis. RESULTS: Over-expression of Smad7 dampened the ability of Ang II to promote ROS synthesis and inhibited the ability of Ang II to decrease functional expression of IκBα. Moreover, Smad7 increased nuclear IκBα expression. Smad7 did not significantly influence the capacity of Ang II to increase protein expression of NF-κB p65. However, immunofluorescence analysis showed that Smad7 reduced nuclear NF-κB p65 level. Further, over-expression of Smad7 promoted GMC apoptosis by inhibiting NF-κB activation, which alleviated the Ang II-promoted proliferation of GMC. CONCLUSIONS: Smad7 influenced NF-κB expression by regulating ROS generation, and induced GMC apoptosis to counter the Ang II-promoted proliferation.

Highly transparent and luminescent lanthanide ion-containing bridged polysilsesquioxanes.

Novel luminescent bridged polysilsesquioxane monoliths of high transparency have been obtained by hydrolysis and condensation of the precursor under acidic conditions. The monoliths were characterized by FTIR spectroscopy, photoluminescence spectroscopy, and SEM, and they have been used as hosts of Eu(3+), Tb(3+) and Nd(3+) ions. The luminescence lifetime of Tb(3+) in this host was 2.1 ms. The interaction between the host and the lanthanide ions could be confirmed by FTIR spectra. The number of water molecules coordinated to the Eu(3+) ions was determined to be one. Incorporation of Nd(3+) as guest resulted in NIR-luminescent materials.