Mechanically robust, flame-retardant poly(lactic acid) biocomposites via combining cellulose nanofibers and ammonium polyphosphate

Expanding the application range of flame-retardant polymer biocomposites remains a huge challenge for a sustainable society. Despite largely enhanced flame retardancy, until now the resultant poly(lactic acid) (PLA) composites still suffer reduced tensile strength and impact toughness due to improper material design strategies. We, herein, demonstrate the design of a green flame retardant additive (ammonium polyphosphate (APP)@cellulose nanofiber (CNF)) via using the cellulose nanofibers (CNFs) as the green multifunctional additives hybridized with ammonium polyphosphate (APP). The results show that PLA composite with 5 wt % loading of APP@CNF can pass the UL-94 V-0 rating, besides a high limited oxygen index of 27.5%, indicative of a significantly enhanced flame retardancy. Moreover, the 5 wt % of APP@CNF enables the impact strength (σi) of the PVA matrix to significantly improve from 7.63 to 11.8 kJ/m2 (increase by 54%), in addition to a high tensile strength of 50.3 MPa for the resultant flame-retardant PLA composite. The enhanced flame retardancy and mechanical strength performances are attributed to the improved dispersion of APP@CNF and its smaller phase size within the PLA matrix along with their synergistic effect between APP and CNF. This work opens up a facile innovative methodology for the design of high-performance ecofriendly flame retardants and their advanced polymeric composites

DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding

Abstract Background Genome-wide association studies (GWASs) have identified dozens of loci associated with gout, but for most cases, the risk genes and the underlying molecular mechanisms contributing to these associations are unknown. This study sought to understand the molecular mechanism of a common genetic variant, rs780093, in the development of gout, both in vitro and in vivo. Results Nuclear receptor binding protein 1 (NRBP1), as a gout risk gene, and its regulatory region, 72 bp upstream of the transcription start site, designated as B1, were identified through integrative analyses of genome-wide genotype and DNA methylation data. We observed elevated NRBP1 expression in human peripheral blood mononuclear cells (PBMCs) from gout patients. In vitro luciferase reporter and protein pulldown assay results showed that DNA methylation could increase the binding of the transcription factor TFAP2A to B1, leading to suppressed gene expression. There results were further confirmed by in vivo bisulfite pyrosequencing showing that hypomethylation on B1 is associated with increased NRBP1 expression in gout patients. Conclusions Hypomethylation at the promoter region of NRBP1 reduces the binding of TFAP2A and thus leads to elevated NRBP1 expression, which might contribute to the development of gout

Divergent mitochondrial responses and metabolic signal pathways secure the azole resistance in Crabtree-positive and negative Candida species

ABSTRACTAzole drugs are the main therapeutic drugs for invasive fungal infections. However, azole-resistant strains appear repeatedly in the environment, posing a major threat to human health. Several reports have shown that mitochondria are associated with the virulence of pathogenic fungi. However, there are few studies on the mechanisms of mitochondria-mediated azoles resistance. Here, we first performed mitochondrial proteomic analysis on multiple Candida species (Candida albicans, Nakaseomyces glabrata, Pichia kudriavzevii, and Candida auris) and analyzed the differentially expressed mitochondrial proteins (DEMPs) between azole-sensitive and azole-resistant Candida species. Subsequently, we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology analysis, and protein-protein interaction network analysis of DEMPs. Our results showed that a total of 417, 165, and 25 DEMPs were identified in resistant C. albicans, N. glabrata, and C. auris, respectively. These DEMPs were enriched in ribosomal biogenesis at cytosol and mitochondria, tricarboxylic acid cycle, glycolysis, transporters, ergosterol, and cell wall mannan biosynthesis. The high activations of these cellular activities, found in C. albicans and C. auris (at low scale), were mostly opposite to those observed in two fermenter species—N. glabrata and P. kudriavzevii. Several transcription factors including Rtg3 were highly produced in resistant C. albicans that experienced a complex I activation of mitochondrial electron transport chain (ETC). The reduction of mitochondrial-related activities and complex IV/V of ETC in N. glabrata and P. kudriavzevii was companying with the reduced proteins of Tor1, Hog1, and Snf1/Snf4.IMPORTANCECandida spp. are common organisms that cause a variety of invasive diseases. However, Candida spp. are resistant to azoles, which hinders antifungal therapy. Exploring the drug-resistance mechanism of pathogenic Candida spp. will help improve the prevention and control strategy and discover new targets. Mitochondria, as an important organelle in eukaryotic cells, are closely related to a variety of cellular activities. However, the role of mitochondrial proteins in mediating azole resistance in Candida spp. has not been elucidated. Here, we analyzed the mitochondrial proteins and signaling pathways that mediate azole resistance in Candida spp. to provide ideas and references for solving the problem of azole resistance. Our work may offer new insights into the connection between mitochondria and azoles resistance in pathogenic fungi and highlight the potential clinical value of mitochondrial proteins in the treatment of invasive fungal infections

Alteration in bile acids profile in Large White pigs during chronic heat exposure.

Bile acids (BAs) are critical for cholesterol homeostasis and new roles in metabolism and endocrinology have been demonstrated recently. It remains unknown whether BA metabolism can be affected by heat stress (HS). The objective of this study was to describe the shifts in serum, hepatic and intestinal BA profiles induced by chronic HS. Twenty-seven Large White pigs weighing 40.8+/-2.7kg were assigned to one of the three treatments: a control group (CON, 23 degrees C), a HS group (33 degrees C), or a pair-fed group (PF, 23 degrees C and fed the same amount as HS group) for 21d. The concentrations of taurine-conjugated BAs (TUDCA and THDCA in serum and TCDCA, TUDCA, THDCA and THCA in liver) were decreased in HS and PF pigs. However, in HS pigs, a reduction in taurine-conjugated BAs (TCBA) correlated with decreased liver genes expression of BA synthesis, conjugation and uptake transport. BA regulated-genes (FXR, TGR5 and FGFR4) in HS pigs and TGR5, FGFR4 and KLbeta in PF pigs were down-regulated in liver. In ileum, total BAs and glycoursodeoxycholic acid concentrations were higher in HS pigs than other groups and PF group, respectively (P<0.05). TCBA (P=0.01) and tauroursodeoxycholic acid (P<0.01) were decreased in PF group. BA transporters (OSTalpha and MRP3) were up-regulated in HS pigs compared with CON and PF pigs, respectively (P<0.01). In cecum, ursodeoxycholic acid was higher in HS (P=0.02) group than CON group. The expression of apical sodium-coupled bile acid transporter (P=0.04) was lower in HS pigs than CON pigs, while OSTbeta (P<0.01) was greater in HS group than PF group. These results suggest that chronic HS suppressed liver activity of synthesis and uptake of TCBA, at least in part, which was independent of reduced feed intake

Additional file 1: Figure S1. of DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding

Work flow diagram. Figure S2. Serum uric acid is regulated by B1 methylation level and NRBP1 expression. a A marginal significant negative association between DNA methylation of B1 and serum uric acid (P value = 0.08). b A significant positive association between NRBP1 expression and serum uric acid (P value = 0.03). Figure S3. Decreased DNA methylation at the promoter region of NRBP1 in gout patients. a The DNA sequence at the promoter region of NRBP1 gene. The CpG sites, designated as B1 to B6, are highlighted in red. b The methylation level for each CpG site indicated in a, was investigated by bisulfite pyrosequencing. Data are represented as mean ± SEM. (*P value <0.01, **P value <0.001, Student’s t test, unpaired, two-sided). (PPTX 1077 kb

Additional file 2: File 1. of DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding

Detailed experimental methods. a Quantitative real-time PCR. b Generation of methylated DNA and luciferase reporter. c Protein pulldown assay. (DOCX 13 kb

Controllable Growth of Lead-Free All-Inorganic Perovskite Nanowire Array with Fast and Stable Near-Infrared Photodetection

Low-dimensional all-inorganic metal halide perovskites have been demonstrated as excellent building blocks for high-performance optoelectronic devices. Although many progresses have been achieved in low-dimensional all-inorganic perovskites, the substitution of toxic Pb is urgent for further optoelectronic applications. Here, we present the growth of lead-free all-inorganic CsSnX3 (X = Cl, Br, and I) perovskite nanowire (NW) arrays on a mica substrate by a solid-source chemical vapor deposition method. All of the lead-free all-inorganic CsSnX3 perovskite NW arrays epitaxially grow on the mica substrate to form equilateral triangles. The band gaps of the as-prepared CsSnX3 perovskite NW arrays decrease from 1.84 to 1.34 eV with X changes from Br to I. The high crystallinity is confirmed by the strong photoluminescence (PL) emission peaks and uniform two-dimensional PL mapping images. In the end, the as-prepared high-quality CsSnI3 perovskite NW array is then configured into a near-infrared photodetector for the first time, exhibiting fast rise and decay time constants of 83.8 and 243.4 ms, respectively. All of the results present an important advance in the field of low-dimensional all-inorganic perovskites

Associations of NR5A2 Gene Polymorphisms with the Clinicopathological Characteristics and Survival of Gastric Cancer

The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679–0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size &gt;5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size &gt;5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed