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Present outlook during COVID-19 about neurology: A new mechanistic insight.
We report a heterojunction Bi2WO6/WS2-x with sulfur vacancies as a broad-spectrum bactericide to efficiently kill Gram-positive and Gram-negative bacteria in vitro and in vivo under visible-light irradiation. Sulfur vacancies in single-layer WS2 make the surface electron-rich. Integration of Bi2WO6 with WS2 enhances the photoelectric activity under visible-light irradiation. Sulfur vacancies promote the generation of radicals and the extraction of membrane phospholipids from bacterial cells. Density functional theory verifies that S vacancies strengthen the interactions between the Bi2WO6/WS2-x surface and H2O, enhancing the generation of ·OH. Two-dimensional correlation spectroscopy analysis reveals that perturbation of β-sheet proteins and formation of outer-sphere surface complexes contribute to the high antibacterial capacity. Bi2WO6/WS2-x accelerates the re-epithelialization and healing of infected wounds in an animal model. Uncommonly, Bi2WO6/WS2-x does not exhibit drug resistance and is biocompatible with human cells. selleck Our results indicate that vacancy-functionalized heterojunctions are potentially promising antibacterial agents by regulating the interface interaction between biology and nanomaterials. Hypoxia-inducible factor-1 (HIF-1) has been implicated in the pathogenesis of choroidal neovascularization (NV) and is an appealing target because it increases multiple pro-angiogenic proteins and their receptors. Acriflavine (ACF) binds HIF-1α and HIF-2α preventing binding to HIF-1β and inhibiting transcriptional activity of HIF-1 and HIF-2. Delivery of ACF to the eye by multiple routes strongly, but transiently, suppresses choroidal NV. We overcame design challenges and loaded highly water soluble ACF into poly(lactic-co-glycolic acid) (PLGA) microparticles (PLGA-ACF MPs) that release ACF in vitro for up to 60 days. Intravitreous injection of PLGA-ACF MPs in mice suppressed choroidal NV for at least 9 weeks and suprachoroidal injection of PLGA-ACF in rats suppressed choroidal NV for at least 18 weeks. Intravitreous, but not suprachoroidal injection, of PLGA-ACF MPs containing 38 μg of ACF in rabbits resulted in modest reduction of full-field electroretinogram (ERG) function. Over the span of 28 days after suprachoroidal injection of PLGA-ACF MP, rabbits had normal appearing retinas on fundus photographs, normal electroretinogram scotopic a- and b-wave amplitudes, no increase in intraocular pressure, and normal retinal histology. The active component of ACF, trypaflavine, had steady-state levels in the low nM range in RPE/choroid > retina for at least 16 weeks with a gradient from the side of the eye where the injection was done to the opposite side. These data suggest that suprachoroidal injection of PLGA-ACF MPs has the potential to provide a durable new treatment for retinal and choroidal vascular diseases. In vitro tissue engineered models are poised to have significant impact on disease modeling and preclinical drug development. Reliable methods to induce microvascular networks in such microphysiological systems are needed to improve the size and physiological function of these models. By systematically engineering several physical and biomolecular properties of the cellular microenvironment (including crosslinking density, polymer density, adhesion ligand concentration, and degradability), we establish design principles that describe how synthetic matrix properties influence vascular morphogenesis in modular and tunable hydrogels based on commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. We apply these design principles to generate endothelial networks that exhibit consistent morphology throughout depths of hydrogel greater than 1 mm. These PEG8a-based hydrogels have relatively high volumetric swelling ratios (>1.5), which limits their utility in confined environments such as microfluidic devices. To overcome this limitation, we mitigate swelling by incorporating a highly functional PEG-grafted alpha-helical poly (propargyl-l-glutamate) (PPLGgPEG) macromer along with the canonical 8-arm PEG8a macromer in gel formation. This hydrogel platform supports enhanced endothelial morphogenesis in neutral-swelling environments. Finally, we incorporate PEG8a-PPLGgPEG gels into microfluidic devices and demonstrate improved diffusion kinetics and microvascular network formation in situ compared to PEG8a-based gels. OBJECTIVES This study aimed at investigating poverty and other correlates of childhood underweight and obesity in two urban regions with lower (Podgorica, Montenegro) and higher economic development (Osijek, Croatia). STUDY DESIGN Comparative study. METHODS A comparative study was conducted on 693 children (52% boys), aged 7 years old (224 from Podgorica and 469 from Osijek). Parents completed the study-specific questionnaire on relevant factors for children's nutritional status. We measured children's height and weight and calculated their body mass index (BMI). International Obesity Task Force cut-off values of BMI were used to assess children's nutritional status. Subjective social position was assessed by the Mac Arthur scale. RESULTS There were more underweight children in Osijek compared with Podgorica, both among boys (5.5% vs. 1.6%) and girls (6.9% vs. 1.0%). Obesity was more frequent in Podgorica than Osijek, both among boys (11.3% vs. 5.9%) and girls (10.0% vs. 4.3%). However, poverty in two cities diminished observed differences in children's nutritional status. The odds for child underweight decreased by 12.2%, while the odds for obesity increased by 3.6% per each paternal BMI unit. The frequency of child obesity was lowered per each step higher on the Mac Arthur scale and with breastfeeding by 23.2% and 68.0%, respectively. CONCLUSIONS We show that a higher economic development is related to less obese children but more underweight children. However, poverty seems to impact nutritionally all children equally, regardless of the regional economic development. Paternal and not maternal BMI is relevant for both extremes in children's nutritional status. Breastfeeding and higher social position independently protect from child obesity.
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