Notes

Hydrothermal carbons/ferrihydrite heterogeneous Fenton reasons along with lower H2O2 usage as well as the effect of graphitization diplomas.
us contributing to gain control in the vestibular afferent input.There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.Rationale Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was less then 1 year, less then 3 spirometric measurements, or less then 100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P  less then  0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.Rationale The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent.Understanding the interactions between neural and musculoskeletal systems is key to identifying mechanisms of functional failure. Mammalian swallowing is a complex, poorly understood motor process. Lesion of the recurrent laryngeal nerve, a sensory and motor nerve of the upper airway, results in airway protection failure (liquid entry into the airway) during swallowing through an unknown mechanism. We examined how muscle and kinematic changes after recurrent laryngeal nerve lesion relate to airway protection in eight infant pigs. read more We tested two hypotheses 1) kinematics and muscle function will both change in response to lesion in swallows with and without airway protection failure, and 2) differences in both kinematics and muscle function will predict whether airway protection failure occurs in lesion and intact pigs. We recorded swallowing with high-speed videofluoroscopy and simultaneous electromyography of oropharyngeal muscles pre- and postrecurrent laryngeal nerve lesion. Lesion changed the relationship bontrol.Directed evolution methods based on high-throughput growth selection enable efficient discovery of enzymes with improved function in vivo. High-throughput selection is particularly useful when engineering oxygenases, which are sensitive to structural perturbations and prone to uncoupled activity. In this work, we combine the principle that reactive oxygen species (ROS) produced by uncoupled oxygenase activity are detrimental to cell fitness with a redox balance-based growth selection method for oxygenase engineering that enables concurrent advancement in catalytic activity and coupling efficiency. As a proof-of-concept, we engineered P450-BM3 for degradation of acenaphthene (ACN), a recalcitrant environmental pollutant. Selection of site-saturation mutagenesis libraries in E. coli strain MX203 identified P450-BM3 variants GVQ-AL and GVQ-D222N, which have both improved coupling efficiency and catalytic activity compared to the starting variant. Computational modeling indicates that the discovered mutations cooperatively optimize binding pocket shape complementarity to ACN, and shift the protein's conformational dynamics to favor the lid-closed, catalytically competent state.
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