RNF40 regulates gene expression in an epigenetic context-dependent manner

Background Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-“suppressed” genes is associated with enhancer activation via FOXL2. Conclusion Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications

Pengembangan Kurikulum Pendidikan Lingkungan di Kota Tangerang Selatan: Bagaimana Mengintegrasikan Deklarasi Tbilisi dalam Kurikulum

This study aims to develop environmental education curriculum based on Tbilisi Declaration. There were five environmental education goals of Tbilisi Declaration namely knowledge, awareness, attitudes, skills, and participation. Curriculum was developed for supporting education policy in South Tangerang, Banten Province, Indonesia. Letter of Education Division South Tangerang City nomor 800/KEP 1222-dikdas/2014 stated environmental education as local curriculum in South Tangerang Elementary School. Curriculum was developed by developmental research. There was four steps to develop curriculum, every steps had three activities, i.e. making, reviewing, and fixing. This study result some standard and basic competences. Research developed environmental education was integrated with thematic subject matter in 1st and 2nd grade, but as monolithic subject matter in 3rd – 6rd grade. Using exiting competence standard from 2014 curriculum and format standard competence 2006 made this curriculum have flexibility to implement for the school that used 2006 or 2013 curriculum

Meta-analysis of Androgen Insensitivity in Preoperative Hormone Therapy in Hypospadias.

OBJECTIVE: To define androgen insensitivity prevalence in hypospadias patients treated with preoperative hormone therapy. MATERIALS AND METHODS: We searched databases that were published in English and Chinese up to September 10, 2014 for our studies. Eligibility criteria were pre-established. Title, abstract, and full-text screenings were conducted by 2 authors independently. Discrepancies were resolved by consensus. Quality assessment of included studies was completed. Meta-analysis was done when appropriate using R, version 3.1.1 for Windows. Heterogeneity among individual studies was tested using the Cochran chi-square Q test and quantified by calculating the I(2) index. RESULTS: Thirteen of 1278 publications met inclusion criteria and were incorporated into this study. Of 306 patients with preoperative hormone therapy, 25 displayed androgen resistance. Meta-analysis demonstrated that the random-effects model generates a pooled estimate of 7.14% (95% confidence interval [CI], 3.16%-15.31%), whereas the fixed-effect model provides an estimate of 14.61% (95% CI, 10.00%-20.85%). Heterogeneity among included studies was found above medium (I(2) = 67.1% [95% CI, 41.2%-81.6%]; P = .0003]. After exclusion of the heterogeneity, both random-effects and fixed-effect models produce a consistent pooled estimate of 6.95% (95% CI, 0%-47.8%). CONCLUSION: We have defined that the prevalence of androgen resistance in hypospadias is 7.14% (95% CI, 3.16%-15.31%). To distinguish isolated hypospadias from patients with androgen insensitivity syndrome, we recommend that androgen-resistant patients should be specifically targeted by molecularly focused diagnosis. Management strategies should include identification of mutations in the androgen receptor gene, timely surgery to repair hypospadias, and long-term follow-up of sexual function and fertility later in life

Reversion of pH-Induced Physiological Drug Resistance: A Novel Function of Copolymeric Nanoparticles

The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this “pH-induced physiological drug resistance” (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion.As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo.<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects.The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect

Development of a postoperative visual function rehabilitation compliance assessment scale for children with congenital cataract: a reliability and validity study

Abstract Objective To develop a comprehensive compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts and to assess its reliability and validity. Method Drawing on the Interactive Model of Health Behavior, we conducted a literature review and semi-structured interviews to create a pool of 36 items. The items underwent rigorous evaluation through the Delphi method, face validity checks, and item analysis, leading to a reduction to 18 items. To assess the scale's reliability and validity, we collected data from 225 parents of children with congenital cataracts. We employed SPSS version 25.0 for data analysis and evaluated construct validity using exploratory factor analysis, content validity, internal consistency reliability, and test–retest reliability. Results The compliance scale for postoperative visual function rehabilitation in children with congenital cataracts comprises 5 dimensions and 18 items. Exploratory factor analysis extracted 5 common factors, with a cumulative variance contribution rate of 68.178%. Item-level content validity index ranged from 0.730 to 1.000, and the content validity index of the scale was 0.963. The total Cronbach's alpha coefficient, split-half reliability, and test–retest reliability of the scale were 0.855, 0.778, and 0.859, respectively. Conclusions The compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts demonstrates acceptable reliability and validity. It serves as a valuable reference for developing standardized nursing programs for these children in clinical practice

miR-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G

miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells

Factors Associated With Perception of Stigma Among Parents of Children With Cleft Lip and Palate: Cross-Sectional Study

BackgroundParents of children with cleft lip with or without cleft palate (CL/P) often face stigmatization, which has a significant impact on their quality of life and mental health. However, to date, there is a lack of comprehensive, multicenter empirical research on parents of children with CL/P in China, particularly those with large-scale samples. ObjectiveThis study aimed to identify major factors that contribute to the perception of stigma experienced by parents of children with CL/P. MethodsA cross-sectional survey was conducted. A total of 104 parents of children diagnosed with CL/P in 2 hospitals were selected by convenience sampling. Demographics and disease information, the Chinese Perception of Stigma Questionnaire, the Center for Epidemiological Studies Depression Scale, and the Social Anxiety Scale were used in this study. Descriptive statistics, t tests, and one-way ANOVA were used to compare the differences between participants’ demographic information and perception of stigma. Multivariable linear regression was performed to assess associations between demographic factors, social anxiety, depression, and perception of stigma. ResultsThe mean scores for the dimensions of perception of stigma, depression, and social anxiety were 22.97 (SD 9.21), 38.34 (SD 8.25), and 22.86 (SD 6.69), respectively. Depression and social anxiety were positively associated with discrimination, while surgery status was a negatively associated variable. Parents with a college education or higher had significantly lower levels of perceived stigma compared to parents with a junior high school education (all P values <.05). These 4 factors explained 40.4% of the total model variance (F8=9.726; P<.001; R2=0.450; adjusted R2=0.404). ConclusionsOur findings highlight a concerning trend of diminished quality of life among parents of children with CL/P. Factors such as parents’ education level, surgery status, depression, and social anxiety are shown to influence the level of stigma experienced. Implementing comprehensive nursing care and providing presurgical support are effective strategies for alleviating parents’ social anxiety, reducing perceived stigma, and preventing depression

Building Solar Cells from Nanocrystal Inks

The use of solution-processed photovoltaics is a low cost, low material-consuming way to harvest abundant solar energy. Organic semiconductors based on perovskite or colloidal quantum dot photovoltaics have been well developed in recent years; however, stability is still an important issue for these photovoltaic devices. By combining solution processing, chemical treatment, and sintering technology, compact and efficient CdTe nanocrystal (NC) solar cells can be fabricated with high stability by optimizing the architecture of devices. Here, we review the progress on solution-processed CdTe NC-based photovoltaics. We focus particularly on NC materials and the design of devices that provide a good p&#8722;n junction quality, a graded bandgap for extending the spectrum response, and interface engineering to decrease carrier recombination. We summarize the progress in this field and give some insight into device processing, including element doping, new hole transport material application, and the design of new devices