Injectable hydrogels embedded with chitosan nanoparticles coated with hyaluronic acid for sequential release of dual drugs.

An effective treatment for some disease, such as the model disease acute retinal necrosis (ARN), requires a combination of different drugs which should be administered at a certain interval. The precise sequential and long-term drug release are the critical questions. In this work, the as-prepared chitosan nanoparticles (CS-NPs) coated with hyaluronic acid (HA) were embedded in the aldehyde ß-cyclodextrin (ACD)/aminated hyaluronic acid (NHA) hydrogels to synthesize injectable hydrogels loaded with dual drugs named DEX-CS-NPs/GCV-Gel and HA-DEX-CS-NPs/GCV-Gel. In the first 24 h and 48 h, the releases of DEX from DEX-CS-NPs/GCV-Gel were 128.5 % and 82.8 % faster than those from HA-DEX-CS-NPs/GCV-Gel, respectively. There was no DEX released from HA-DEX-CS-NPs/GCV-Gel at the first 7 h, which has never been reported before, although some hydrogel systems loaded with different drugs release different drugs simultaneously at different rate which have been well studied. This is a good start of a precise sequence release. The composite hydrogels possessed appropriate rheology, gel time, degradation performance, and ideal cytocompatibility. The injectable hydrogel loaded with dual drugs presenting a precise sequential and long-term release has great potential in the treatment of diseases requiring combinations of drugs being released sequentially at different treating stages.

Prevalence of myopia: A large-scale population-based study among children and adolescents in weifang, china.

Purpose: This study aimed to determine the prevalence of myopia among school-aged children and adolescents at the whole city level of Weifang, China. Methods: This study was a large scale school-based cross-sectional study among children and adolescents aged 5-20 years old. Participants were selected by the school-based registration system in 2020. All the subjects underwent spherical equivalent (SE) error with non-cycloplegic autorefraction measurement. Myopia was defined as an SE refraction of ≤-0.75 diopters (D) and graded into low myopia (-0.75 to -3.00 D), moderate myopia (-3.01 to -5.99 D), and high myopia (≤-6.00 D). Results: A total of 1,059,838 participants were eligible for this survey and 1,013,206 (95.6% participation rate) were selected through data quality control, which comprised 17 districts/counties and 1,254 schools, including 861 elementary schools, 313 middle schools, and 80 high schools. The mean age of participants was 11.57 ± 3.36 years (5-20 years), and the male-to-female ratio was 1.11. The whole city-level prevalence of total myopia was 75.35%. The prevalence of total myopia among the students in the Hanting District was 45.47%, but ≈82.37% of students living in Changyi have myopia. The overall prevalence of low myopia in elementary, middle, and high school students was 48.56, 47.30, and 31.62%, respectively, while high myopia (SE ≤ -6.00 D) prevalence was 1.12, 8.89, and 20.12%, respectively. The overall prevalence of myopia increased fastest in children aged 7-9 years old. The prevalence of high myopia was 7.59% for girls and 6.43% for boys, respectively (p < 0.001). The prevalence of myopia increased with increasing age and grade, but SE decreased with increasing age and grade. Conclusions: The current investigation demonstrated a high proportion of myopia among school students in the city of Weifang, and gradually increased with age, and the prevalence of myopia was the highest in Changyi areas. The high myopia prevalence for girls was higher than that in boys.

Circular RNA circZNF292 regulates H2 O2 -induced injury in human lens epithelial HLE-B3 cells depending on the regulation of the miR-222-3p/E2F3 axis.

Circular RNAs (circRNAs) play important roles in the pathogenesis of age-related cataract (ARC). CircRNA zinc finger protein 292 (circZNF292, hsa_circ_0004058) is downregulated in ARC lens capsules. Here, we focused on its precise roles in oxidative stress underlying the pathogenesis of ARC. CircZNF292, microRNA (miR)-222-3p, and E2F transcription factor 3 (E2F3) were quantified by quantitative real-time polymerase chain reaction or western blot. Cell viability was assessed by the cell counting kit-8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. The activities of superoxide dismutase, catalase, and malondialdehyde were measured using the corresponding assay kit. Targeted correlations among circZNF292, miR-222-3p, and E2F3 were verified by the dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Our data showed that circZNF292 was downregulated in ARC tissues and H2 O2 -treated human lens epithelial B3 (HLE-B3) cells. Increased expression of circZNF292 alleviated H2 O2 -induced cell viability suppression, apoptosis promotion, and oxidative stress enhancement. Mechanistically, circZNF292 directly targeted miR-222-3p, and circZNF292 regulated E2F3 expression through miR-222-3p. MiR-222-3p was a functional mediator of circZNF292 in modulating H2 O2 -induced injury in HLE-B3 cells. Furthermore, reduced level of miR-222-3p ameliorated H2 O2 -induced HLE-B3 cell damage by upregulating E2F3. Our present study demonstrated that increased expression of circZNF292 ameliorated H2 O2 -induced injury in HLE-B3 cells at least in part through the miR-222-3p/E2F3 axis, highlighting a novel insight into the involvement of circRNAs in the pathogenesis of ARC.

Brønsted/Lewis acid sites synergistically promote the initial C-C bond formation in the MTO reaction.

The methanol-to-olefin (MTO) reaction is an active field of research due to conflicting mechanistic proposals for the initial carbon-carbon (C-C) bond formation. Herein, a new methane-formaldehyde pathway, a Lewis acid site combined with a Brønsted acid site in zeolite catalysts can readily activate dimethyl ether (DME) to form ethene, is identified theoretically. The mechanism involves a hydride transfer from Al-OCH3 on the Lewis acid site to the methyl group of the protonated methanol molecule on the adjacent Brønsted acid site leading to synchronous formation of methane and Al-COH2 + (which can be considered as formaldehyde (HCHO) adsorbed on the Al3+ Lewis acid sites). The strong electrophilic character of the Al-COH2 + intermediate can strongly accelerate the C-C bond formation with CH4, as indicated by the significant decrease of activation barriers in the rate-determining-step of the catalytic processes. These results highlight a synergy of extra-framework aluminum (EFAl) Lewis and Brønsted sites in zeolite catalysts that facilitates initial C-C bond formation in the initiation step of the MTO reaction via the Al-COH2 + intermediate.