High-performance multifunctional polyvinyl alcohol/starch based active packaging films compatibilized with bioinspired polydopamine nanoparticles.

Bioinspired polydopamine (PDA) nanoparticles were synthesized and explored as functional compatibilizers in polyvinyl alcohol/starch (PVA/ST) matrix to develop high-performance multifunctional packaging film. The effect of the addition of PDA on the microstructural, mechanical, thermal, water vapor barrier, ultraviolet (UV)/high-energy blue light (HEBL) blocking, thermal insulating and antioxidant properties of PVA/ST composite films was fully investigated. Results demonstrated that the added PDA nanoparticles were evenly dispersed in the PVA/ST matrix, providing compact and dense nanocomposite films due to their compatibilization effect. Compared with virgin PVA/ST film, the resulting PVA/ST/PDA nanocomposite films exhibited greatly improved tensile strength, toughness, thermal stability, and water vapor barrier ability. Furthermore, the presence of PDA endowed PVA/ST composite film with excellent UV/HEBL blocking, thermal insulating as well as antioxidant functions. Thus, such high-performance multifunctional nanocomposite films hold the potential of protecting food quality against photothermal oxidative deterioration and extend food shelf life.

Fabrication of highly transparent and multifunctional polyvinyl alcohol/starch based nanocomposite films using zinc oxide nanoparticles as compatibilizers.

This work explored biodegradable polyvinyl alcohol/starch (PVA/ST) film compatibilized by rod-like ZnO nanofillers as multifunctional food packaging materials. The influence of rod-like ZnO nanofillers on the microstructural, UV-shielding, antibacterial, mechanical, thermal, together with water barrier performances of PVA/ST composite films was fully studied. Results revealed that rod-like ZnO nanofillers could be uniformly distributed into the PVA/ST matrix, playing the role of compatibilizers to provide compact and dense nanocomposite films. The resulting nanocomposite films presented greatly improved mechanical and water vapor barrier properties as compared to virgin PVA/ST film. Moreover, the well distributed ZnO endowed PVA/ST film with excellent antimicrobial activity against both E. coli and S. aureus, together with outstanding UV-shielding capability meanwhile retaining highly optical transparency (approximately 90%). The developed PVA/ST/ZnO films were tested for packaging fresh-cut carrot slices to prevent microbial infection and prolong their shelf life. These results indicated that the developed highly transparent and multifunctional PVA/ST/ZnO nanocomposite films possess broad application prospects in active food packaging field.

Improved mechanical, water vapor barrier and UV-shielding properties of cellulose acetate films with flower-like metal-organic framework nanoparticles.

Flower-like metal-organic frameworks (Cu-MOF) nanoparticles are successfully synthesized and incorporated into cellulose acetate (CA) matrix to prepare CA-based functional nanocomposite films via a simple solution-casting method. The effect of the incorporation of flower-like Cu-MOF on the morphological, mechanical, thermal, surface wettability, water vapor barrier, cytotoxicity, photostability and UV-shielding properties of CA films is fully investigated. Results reveal that the flower-like Cu-MOF has good compatibility with CA, providing uniform and compact nanocomposite films. The as-prepared nanocomposite films show improved mechanical properties, surface hydrophobicity, water vapor barrier ability compared to neat CA film, and exhibit super UV-shielding capability through the entire UV regions meanwhile retaining a high visible transparency. Moreover, the high transparency and UV-shielding ability of the nanocomposite films can be still maintained even after continuous UV-light (365 nm) irradiation for 12 h. In addition, MTT cytotoxicity assays towards normal human liver cells (HL-7702) reveal high cell viability (over 80%) and good biocompatibility for the CA/Cu-MOF nanocomposite films. These results indicate that the CA/Cu-MOF nanocomposite films with obviously improved physical and functional performances hold significant potential for transparent packaging and UV-protection applications.

Association between RBMS1 gene rs7593730 and BCAR1 gene rs7202877 and Type 2 diabetes mellitus in the Chinese Han population.

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 are related to type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of the 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970 controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined their association with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP alleles and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had significantly decreased T2DM risk compared to homozygous carriers of TT (P=0.038, OR 0.44, 95% CI 0.20-0.96). In the recessive model, the GG genotype GG had significantly decreased T2DM risk compared to GT+TT (P=0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of CT and TT genotype had significantly decreased T2DM risk compared to the carriers of CC genotype (CT: CC P=0.038, OR 0.71, 95% CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95% CI 0.13-0.76). In a dominant model, TT+CT: CC (P=0.013, OR 0.673, 95% CI 0.49-0.92) and in a recessive model, TT: CT+CC (P=0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had significantly decreased T2DM risk compared to the carriers of C (P=0.002, OR 0.65, 95% CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.

Overexpression of Pyrabactin Resistance-Like Abscisic Acid Receptors Enhances Drought, Osmotic, and Cold Tolerance in Transgenic Poplars.

Abscisic acid (ABA) has been known participate in a wider range of adaptive responses to diverse environmental abiotic stresses such as drought, osmosis, and low temperatures. ABA signaling is initiated by its receptors PYR/PYL/RCARs, a type of soluble proteins with a conserved START domain which can bind ABA and trigger the downstream pathway. Previously, we discovered that poplar (Populus trichocarpa) genome encodes 14 PYR/PYL/RCAR orthologs (PtPYRLs), and two of them, PtPYRL1 and PtPYRL5 have been functionally characterized to positively regulate drought tolerance. However, the physiological function of these ABA receptors in poplar remains uncharacterized. Here, we generated transgenic poplar plants overexpressing PtPYRL1 and PtPYRL5 and found that they exhibited more vigorous growth and produced greater biomass when exposed to drought stress. The improved drought tolerance was positively correlated with the key physiological responses dictated by the ABA signaling pathway, including increase in stomatal closure and decrease in leaf water loss. Further analyses revealed that overexpression lines showed improved capacity in scavenging reactive oxygen species and enhanced the activation of antioxidant enzymes under drought stress. Moreover, overexpression of PtPYRL1 or PtPYRL5 significantly increased the poplar resistance to osmotic and cold stresses. In summary, our results suggest that constitutive expression of PtPYRL1 and PtPYRL5 significantly enhances the resistance to drought, osmotic and cold stresses by positively regulating ABA signaling in poplar.

A survey of the pyrabactin resistance-like abscisic acid receptor gene family in poplar.

The conserved PYR/PYL/RCAR family acts as abscisic acid (ABA) receptors for land plants to adapt to terrestrial environments. Our recent study reported that the exogenous overexpression of poplar PtPYRL1 and PtPYRL5, the PYR/PYL/RCAR orthologs, promoted the sensitivity of transgenic Arabidopsis to ABA responses. Here, we surveyed the PtPYRL family in poplar, and revealed that although the sequence and structure are relatively conserved among these receptors, PtPYRL members have differential expression patterns and the sensitivity to ABA or drought treatment, suggesting that PtPYRLs might be good candidates to a future biotechnological use to enhance poplar resistance to water-stress environments.

Overexpression of Poplar Pyrabactin Resistance-Like Abscisic Acid Receptors Promotes Abscisic Acid Sensitivity and Drought Resistance in Transgenic Arabidopsis.

Drought stress is an important environmental factor limiting productivity of plants, especially fast growing species with high water consumption like poplar. Abscisic acid (ABA) is a phytohormone that positively regulates seed dormancy and drought resistance. The PYR1 (Pyrabactin Resistance 1)/ PYRL (PYR-Like)/ RCAR (Regulatory Component of ABA Receptor) (PYR/PYL/RCAR) ABA receptor family has been identified and widely characterized in Arabidopsis thaliana. However, their functions in poplars remain unknown. Here, we report that 2 of 14 PYR/PYL/RCAR orthologues in poplar (Populus trichocarpa) (PtPYRLs) function as a positive regulator of the ABA signal transduction pathway. The Arabidopsis transient expression and yeast two-hybrid assays showed the interaction among PtPYRL1 and PtPYRL5, a clade A protein phosphatase 2C, and a SnRK2, suggesting that a core signalling complex for ABA signaling pathway exists in poplars. Phenotypic analysis of PtPYRL1 and PtPYRL5 transgenic Arabidopsis showed that these two genes positively regulated the ABA responses during the seed germination. More importantly, the overexpression of PtPYRL1 and PtPYRL5 substantially improved ABA sensitivity and drought stress tolerance in transgenic plants. In summary, we comprehensively uncovered the properties of PtPYRL1 and PtPYRL5, which might be good target genes to genetically engineer drought-Resistant plants.

Cadmium impairs ion homeostasis by altering K+ and Ca2+ channel activities in rice root hair cells.

Cadmium (Cd2+) interferes with the uptake, transport and utilization of several macro- and micronutrients, which accounts, at least in part, for Cd2+ toxicity in plants. However, the mechanisms underlying Cd2+ interference of ionic homeostasis is not understood. Using biophysical techniques including membrane potential measurements, scanning ion-selective electrode technique for non-invasive ion flux assays and patch clamp, we monitored the effect of Cd2+ on calcium (Ca2+) and potassium (K+) transport in root hair cells of rice. Our results showed that K+ and Ca2+ contents in both roots and shoots were significantly reduced when treated with exogenous Cd2+. Further studies revealed that three cellular processes may be affected by Cd2+, leading to changes in ionic homeostasis. First, Cd2+ -induced depolarization of the membrane potential was observed in root hair cells, attenuating the driving force for cation uptake. Second, the inward conductance of Ca2+ and K+ was partially blocked by Cd2+, decreasing uptake of K+ and Ca2+ . Third, the outward K+ conductance was Cd2+ -inducible, decreasing the net content of K+ in roots. These results provide direct evidence that Cd2+ impairs uptake of Ca2+ and K+, thereby disturbing ion homeostasis in plants.

IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo.

BACKGROUND: The transcription factor IRF4 is involved in several T-cell-dependent chronic inflammatory diseases. To elucidate the mechanisms for pathological cytokine production in colitis, we addressed the role of the IRF transcription factors in human inflammatory bowel disease (IBD) and experimental colitis. METHODS: IRF levels and cytokine production in IBD patients were studied as well as the effects of IRF4 deficiency in experimental colitis. RESULTS: In contrast to IRF1, IRF5, and IRF8, IRF4 expression in IBD was augmented in the presence of active inflammation. Furthermore, IRF4 levels significantly correlated with IL-6 and IL-17 mRNA expression and to a lesser extent with IL-22 mRNA expression in IBD. To further explore the role of IRF4 under in vivo conditions, we studied IRF4-deficient and wildtype mice in experimental colitis. In contrast to DSS colitis, IRF4 deficiency was protective in T-cell-dependent transfer colitis associated with reduced RORα/γt levels and impaired IL-6, IL-17a, and IL-22 production, suggesting that IRF4 acts as a master regulator of mucosal Th17 cell differentiation. Subsequent mechanistic studies using database analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assays identified a novel IRF4 binding site in the IL-17 gene promoter. Overexpression of IRF4 using retroviral infection induced IL-17 production and IL-17 together with IL-6 induced RORγt expression. CONCLUSIONS: IRF4 can directly bind to the IL-17 promotor and induces mucosal RORγt levels and IL-17 gene expression thereby controlling Th17-dependent colitis. Targeting of this molecular mechanism may lead to novel therapeutic approaches in human IBD.

IRF4 selectively controls cytokine gene expression in chronic intestinal inflammation.

The authors previously showed that interferon regulatory factor (IRF)4 knockout mice are protected from experimental oxazolone and TNBS colitis. Here the effect of IRF4 on the expression of pro- and anti-inflammatory cytokines in TNBS colitis and long-term CD45RB(high) transfer colitis is examined. In TNBS colitis, no differences were found in interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha expression between IRF4 knockout and wild-type mice. However, significant differences were detected in IL-6 and IL-17 production. Upon treatment with hyper-IL-6, IRF4(-/-) mice lost their protective properties towards TNBS application. Hyper-IL-6 application induced IL-6 mRNA, but not IL-17 mRNA expression, suggesting that IL-6 deficiency is not primarily responsible for the lack of IL-17 production. T-bet and GATA-3 mRNA expressions were not affected upon IL-6 application. In transfer colitis, colonic cytokine mRNA analysis revealed a reduced production of IL-6 in IRF4(-/-) reconstituted mice in the long-term course. In contrast, several other cytokines did not differ between the two groups (e.g. TNF-alpha and IL-10). Measurement of supernatants from splenic mononuclear cells revealed a significant difference in IL-6 and IL-17 production between the two groups. These findings suggest that IRF4 selectively regulates cytokine gene expression in chronic inflammation. IRF4 therefore emerges as an attractive target for the therapy of chronic intestinal inflammation. Blocking IRF4 might be an interesting option to modulate inflammation in the advanced state of inflammation.

The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6.

The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transplantation with CD4+CD45RB(hi) T cells, adoptive transfer of wild-type but not IRF4-deficient T cells resulted in severe colitis. Furthermore, IRF4-deficient mice were protected from T cell-dependent chronic intestinal inflammation in trinitrobenzene sulfonic acid- and oxazolone-induced colitis. In addition, IRF4-deficient mice with induced colitis had reduced mucosal IL-6 production, and IRF4 was required for IL-6 production by mucosal CD90+ T cells, which it protected from apoptosis. Finally, the protective effect of IRF4 deficiency could be abrogated by systemic administration of either recombinant IL-6 or a combination of soluble IL-6 receptor (sIL-6R) plus IL-6 (hyper-IL-6). Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell-dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs.

Suppression of TNF-alpha production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines.

Endotoxin-induced cytokine production is an important mechanism in the development of several types of liver damage. Methionine, some of its precursors and metabolites were reported to have protective effects against such injury. The aim of this study was to investigate whether methionine, its precursors or metabolites [phosphatidylcholine, choline, betaine, S-adenosylmethionine (SAM)] have a modulating effect on tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated human mononuclear leukocytes and whether SAM-dependent polyamines (spermidine, spermine) are mediators of SAM-induced inhibition of TNF-alpha synthesis. Methionine and betaine had a moderate stimulatory effect on TNF-alpha production, whereas phosphatidylcholine (ID(50) 5.4 mM), SAM (ID(50) 131 microM), spermidine (ID(50) 4.5 microM) and spermine (ID(50) 3.9 microM) had a predominantly inhibitory effect. Putrescine did not alter TNF-alpha release. Inhibitors of polyamine synthesis that blocked either putrescine (difluoromethylornithine) or spermine (CGP48664A) production did not affect TNF-alpha synthesis. Endotoxin stimulation of leukocytes did not alter the intracellular levels of polyamines. In addition, supplementation with SAM did not change the intracellular concentration of either polyamine measured. We conclude that phosphatidylcholine-induced immunosuppression is not caused by methionine and polyamines are not involved in SAM-induced inhibition of TNF-alpha production. The limitation of TNF-alpha release by spermidine is specific and is not due to its conversion into spermine.