Induction from the ChREBP Isoform Is Essential for GlucoseStimulated Cell Expansion

Preterm birth (PTB) and threatened preterm labor (TPL), an important pre-PTB state, are major obstetric complications during pregnancy. However, their triggers have not been fully elucidated. The vagina is dominated by Lactobacillus species (categorized as community state types; CSTs I, II, III, and V) or by mixed anaerobes (CST IV). An abundance of the latter is associated with bacterial vaginosis (BV) and BV-triggered PTB/TPL. To identify factors that influence the diversity of vaginal microbiota associated with BV and CST IV (BV-type) bacterial profile, we performed a bioinformatic analysis of the microbial taxa using 16S rRNA amplicon sequencing data of bacterial genome in oral, vaginal, and rectal samples collected from 58 pregnant Japanese women. Interestingly, common residence of BV-associated bacteria in the vagina and rectum was individually detected in the CST IV (non-Lactobacillus dominated) group by species-level Spearman correlation coefficient analysis, suggesting that the rectum acts as a reservoir of BV-associated bacterial species in the CST IV group. The current study provides evidence of bacterial co-residence in vagina and rectum in the non-Lactobacillus dominated group, which could be targeted to reduce the risk of preterm incidence in pregnancy.Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. Mizoribine clinical trial We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.Modern society is currently (and probably more than ever) immersed in the changing concept of food, seeking the beneficial functions of foods rather than only as a mean to quench hunger and support basic nutritional needs [...].The reversal of daptomycin resistance in MRSA to a daptomycin-susceptible phenotype following prolonged passage in selected β-lactams occurs coincident with the accumulation of multiple point mutations in the mprF gene. MprF regulates surface charge by modulating the content and translocation of the positively charged cell membrane phospholipid, lysyl-phosphatidylglycerol (LPG). The precise cell membrane adaptations accompanying such β-lactam-induced mprF perturbations are unknown. This study examined key cell membrane metrics relevant to antimicrobial resistance among three daptomycin-resistant MRSA clinical strains, which became daptomycin-susceptible following prolonged exposure to cloxacillin ('daptomycin-resensitized'). The causal role of such secondary mprF mutations in mediating daptomycin resensitization was confirmed through allelic exchange strategies. The daptomycin-resensitized strains derived either post-cloxacillin passage or via allelic exchange (vs. their respective daptomycin-resistant strains) showed the following cell membrane changes (i) enhanced BODIPY-DAP binding; (ii) significant reductions in LPG content, accompanied by significant increases in phosphatidylglycerol content (p less then 0.05); (iii) no significant changes in positive cell surface charge; (iv) decreased cell membrane fluidity (p less then 0.05); (v) enhanced carotenoid content (p less then 0.05); and (vi) lower branched chain fatty acid profiles (antiso- vs. iso-), resulting in increases in saturated fatty acid composition (p less then 0.05). Overall, the cell membrane characteristics of the daptomycin-resensitized strains resembled those of parental daptomycin-susceptible strains. Daptomycin resensitization with selected β-lactams results in both definable genetic changes (i.e., mprF mutations) and a number of key cell membrane phenotype modifications, which likely facilitate daptomycin activity.In western Texas, most wetlands are fed from precipitation runoff, making them sensitive to drought regimes, anthropogenic land-use activities in their surrounding watersheds, and the interactive effect between these two factors. We surveyed adult odonates in 133 wetlands (49 in grassland settings, 56 in cropland, and 28 in urban areas) in western Texas from 2003-2020; 33 species were recorded. Most species were widespread generalists, but urban wetlands had the highest species richness, as well as the most unique species of any of the three wetland types. Non-metric, multidimensional scaling ordination revealed that the odonate community in urban wetlands was distinctly different in composition than the odonates in non-urban wetlands. Urban wetlands were smaller in surface area than the other wetland types, but because they were fed from more consistently available urban runoff rather than seasonal precipitation, they had longer hydroperiods, particularly during a multi-year drought when wetlands in other land-cover contexts were dry. This anthropogenically enhanced water supply was associated with higher odonate richness despite presumably impaired water quality, indicating that consistent and prolonged presence of water in this semi-arid region was more important than the presence of native land cover within which the wetland existed. Compared to wetlands in the regional grassland landscape matrix, wetlands in agricultural and urban areas differed in hydroperiod, and presumably also in water quality; these effects translated to differences in the regional odonate assemblage by surrounding land-use type, with the highest richness at urban playas. Odonates in human environments may thus benefit through the creation of a more reliably available wetland habitat in an otherwise dry region.Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147-150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.This study assessed the association between serum vitamin E levels and hand grip strength (HGS) in community-dwelling adults data of 1011 men aged 50 years and older and 1144 postmenopausal women were analyzed. Low HGS was defined as HGS below the sex-stratified median value. Proportion of low HGS was the greatest in the lowest quintile of serum vitamin E level ( 0.05). Individuals with the lowest quintile vitamin E level had elevated odds of low HGS independent of covariates, findings which merit further validation.Current in vitro models have significant limitations for new respiratory disease research and rapid drug repurposing. Lung on a chip (LOAC) technology offers a potential solution to these problems. However, these devices typically are fabricated from polydimethylsiloxane (PDMS), which has small hydrophobic molecule absorption, which hinders the application of this technology in drug repurposing for respiratory diseases. Off-stoichiometry thiol-ene (OSTE) is a promising alternative material class to PDMS. Therefore, this study aimed to test OSTE as an alternative material for LOAC prototype development and compare it to PDMS. We tested OSTE material for light transmission, small molecule absorption, inhibition of enzymatic reactions, membrane particle, and fluorescent dye absorption. Next, we microfabricated LOAC devices from PDMS and OSTE, functionalized with human umbilical vein endothelial cell (HUVEC) and A549 cell lines, and analyzed them with immunofluorescence. We demonstrated that compared to PDMS, OSTE has similar absorption of membrane particles and effect on enzymatic reactions, significantly lower small molecule absorption, and lower light transmission. Consequently, the immunofluorescence of OSTE LOAC was significantly impaired by OSTE optical properties. In conclusion, OSTE is a promising material for LOAC, but optical issues should be addressed in future LOAC prototypes to benefit from the material properties.Twenty weaned piglets with initial body weight of 6.83 ± 0.33 kg (21 day of age, LYD) were randomly assigned to four treatments for a two-week feeding trial to determine the effects of different dietary zinc on nutrient digestibility, intestinal health, and microbiome of weaned piglets. The dietary treatments included a negative control (CON), standard ZnO (ZnO, 2500 ppm), zinc chelate with glycine (Chelate-ZnO, 200 ppm), and nanoparticle-sized ZnO (Nano-ZnO, 200 ppm). At 0 to 1 week, the diarrhea score was decreased in the CON group compared with the ZnO, Chelate-ZnO, and Nano-ZnO group. In overall period, the ZnO and Nano-ZnO groups exhibited improved diarrhea scores compared to the CON group. The apparent total tract digestibility of dry matter and gross energy was the lowest in the CON group after one week. Compared to the ZnO group, the chelate-ZnO group exhibited higher proportion of T-bet+ and FoxP3+ T cells and the nano-ZnO group had higher numbers of RORgt+ and GATA3+ T cells in the mesenteric lymph nodes. ZnO group increased IL-6 and IL-8 levels in the colon tissues and these positive effects were observed in both chelate ZnO and nano-ZnO groups with lower level. The 16S rRNA gene analysis showed that the relative abundance of Prevotella was higher in the ZnO-treated groups than in the CON group and that of Succinivibrio was the highest in the nano-ZnO group. The relative abundance of Lactobacillus increased in the ZnO group. In conclusion, low nano-ZnO levels have similar effects on nutrient digestibility, fecal microflora, and intestinal immune profiles in weaning pigs; thus, nano-ZnO could be used as a ZnO alternative for promoting ZnO utilization and intestinal immunity.