Needleless eletrospinning of polystyrene fibers with an oriented surface line texture

We have demonstrated that polystyrene (PS) nanofibers having an ordered surface line texture can be produced on a large scale from a PS solution of acetone and N,N&prime;-dimethylformamide (2/1, vol/vol) by a needleless electrospinning technique using a disc as fiber generator. The formation of the unusual surface feature was investigated and attributed to the voids formed on the surface of jets due to the fast evaporation of acetone at the early stage of electrospinning, and subsequent elongation and solidification turning the voids into ordered lines on fiber surface. In comparison with the nanofibers electrospun by a conventional needle electrospinning using the same solution, the disc electrospun fibers were finer with similar diameter distribution. The fiber production rate for the disc electrospinning was 62 times higher than that of the conventional electrospinning. Fourier transform infrared spectroscopy and X-ray diffraction measurements indicated that the PS nanofibers produced from the two electrospinning techniques showed no significant difference in chemical component, albeit slightly higher crystallinity in the disc spun nanofibers.<br /

Comparison of the Biochemical Composition and Nutritional Quality Between Diploid and Triploid Hong Kong Oysters, Crassostrea hongkongensis

This study is the first systematic comparison of the biochemical composition and nutritional quality between diploid and triploid Hong Kong oysters, Crassostrea hongkongensis. Results showed that in the reproductive season, the glycogen content in five tissues (gill, mantle, adductor muscle, labial palps and gonad) was significantly higher (P &lt; 0.05) in triploids than in diploids, with odds ratios (ORs) of 96.26, 60.17, 72.59, 53.56, and 128.52%, respectively. In the non-reproductive phase, significant differences in glycogen content (P &lt; 0.05) between diploid and triploid oysters existed only in gill and gonad. In both diploid and triploid Hong Kong oysters, quantitative real-time PCR analysis of the glycogen synthesis gene (ChGS) and glycogen phosphorylase gene (ChGP) showed that the gene expression patterns matched the pattern of variation in glycogen content. Moreover, in both the reproductive and the non-reproductive phases, triploid Hong Kong oysters had a well balance of essential amino acids and were thus a well source of high-quality protein. Surprisingly, in both phases, significantly higher (P &lt; 0.05) percentages of four essential fatty acids (α-linolenic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid) were observed in triploids than in diploids. Additionally, the ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) was much higher in triploids than that in diploids. Variations in Biochemical composition were consistent with the relative expression of the citrate synthase gene (ChCS) and the α-ketoglutarate dehydrogenase gene (ChKD), which are key enzyme genes of the tricarboxylic acid cycle. Overall, the triploid Hong Kong oyster has a better nutritional value and taste than the diploid in terms of glycogen content, protein quality and fatty acid content

Analysis of in situ Transcriptomes Reveals Divergent Adaptive Response to Hyper- and Hypo-Salinity in the Hong Kong Oyster, Crassostrea hongkongensis

Crassostrea hongkongensis, a commercially valuable aquaculture species dwelling in estuaries along the coast of the South China Sea, is remarkable for its eurysalinity traits that enable its successful colonization of diverse osmotic niches ranging from near freshwater to seawater. In order to elucidate how this oyster copes with coastal waters with immense salinity differences, we performed in situ transcriptomic analysis (RNA-seq) to characterize the global expression patterns of oysters distributed across naturally formed salinity gradients in Zhenhai Bay along the northern coast of the South China Sea. Principal component analysis reveals distinct expression profiles of oysters living in the extreme conditions of hypo-salinity and hyper-salinity. Compared with the situation of optimal salinity for oyster growth, hypo-salinity mainly regulated expression of genes involved in FoxO and oxytocin signaling, tight junction and several immune pathways, while hyper-salinity altered gene expression implicated in amino acid metabolism, AMPK and PI3K-AKt signaling pathways, demonstrating the complexity and plasticity of transcriptomic expression underpinning oyster eurysalinity. Furthermore, the expression patterns of several genes correlated with salinity gradients reveals the fine-tuned coordination of molecular networks necessary for adaptive homeostasis in C. hongkongensis. In conclusion, a striking capacity and distinct patterns of transcriptomic expression contribute to eurysalinity adaptation in C. hongkongensis, which provides new mechanistic insights into the adaptive plasticity and resilience of marine mollusks

NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses

SummaryUnderstanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1−/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses

Dendritic Cells Are Critical for the Activation and Expansion of Vδ2+ T Cells After Allogeneic Hematopoietic Transplantation

γδ T cells perform antitumor and antiviral effector functions and are involved in both innate and adaptive immunity. Vδ2+ T cells represent the predominant γδ T subset in the peripheral blood of healthy subjects. Vδ2+ T cells can be selectively activated and expanded by phosphoantigens (pAgs). Dendritic cells (DCs), as potent antigen-presenting cells, are capable of mediating pAgs–triggered Vδ2+ T cells expansion. However, the association between DCs and Vδ2+ T cell recovery in the context of hematopoietic stem cell transplantation (HSCT) remains unclear. We previously demonstrated that the recovery of Vδ2+ T cells was hampered and inversely correlated with Epstein-Barr virus (EBV) reactivation in patients undergoing haploidentical HSCT (haploHSCT). Whether Vδ2+ T cells from haploHSCT recipients can be expanded by stimulation with aminobisphosphonates or pAg–presenting DCs is of particular interest. Herein, we showed that Vδ2+ T cells recovered after haploHSCT failed to expand after ex-vivo stimulation with pamidronate. In addition, we found that the recovery of DC subsets was significantly decreased, and the concentration of myeloid DCs (mDCs) correlated significantly with Vδ2+ T cell recovery in the setting of allogeneic HSCT. Furthermore, coculture of peripheral lymphocytes from recipients with monocyte-derived and pamidronate-pretreated autologous or allogeneic DCs induced the successful expansion of Vδ2+ T cells. Of note, allogeneic DCs from third-party donors stimulated a significantly higher efficiency of Vδ2+ T cell expansion than autologous DCs. More importantly, the memory features were well-retained and the cytotoxic cytokines-production capacity was significantly enhanced in the expanded Vδ2+ T cells. Taken together, these results suggest that the frequency and function of DCs are critical for the recovery of Vδ2+ T cells after allogeneic HSCT. The fact that vigorous expansions of Vδ2+ T cells were induced by phosphoantigen-pretreated DCs, especially by allogeneic third-party DCs, provides additional options for the development of individualized immunotherapy strategies that utilize the anti-viral and anti-leukemic effects of γδ T cells in the context of hematopoietic transplantation

Polysaccharide Extracted from Laminaria japonica

This study aimed to determine the effect of topically applied Laminaria polysaccharide (LP) on skin aging. We applied ointment containing LP (10, 25, and 50 μg/g) or vitamin E (10 μg/g) to the dorsal skin of aging mice for 12 months and young control mice for 4 weeks. Electron microscopy analysis of skin samples revealed that LP increased dermal thickness and skin collagen content. Tissue inhibitor of metalloprotease- (TIMP-) 1 expression was upregulated while that of matrix metalloproteinase- (MMP-) 1 was downregulated in skin tissue of LP-treated as compared to untreated aging mice. Additionally, phosphorylation of c-Jun N-terminal kinase (JNK) and p38 was higher in aging skin than in young skin, while LP treatment suppressed phospho-JNK expression. LP application also enhanced the expression of antioxidative enzymes in skin tissue, causing a decrease in malondialdehyde levels and increases in superoxide dismutase, catalase, and glutathione peroxidase levels relative to those in untreated aging mice. These results indicate that LP inhibits MMP-1 expression by preventing oxidative stress and JNK phosphorylation, thereby delaying skin collagen breakdown during aging

Finerenone in Patients with Chronic Kidney Disease and Type 2 Diabetes: FIDELIO-DKD subgroup from China

Background: This prespecified subgroup analysis of the FIDELIO-DKD trial aimed to evaluate the efficacy and safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in China. Methods: Three hundred and seventy-two participants were recruited from 67 centers in China and randomized 1:1 to oral finerenone or placebo with standard therapy for T2DM. The primary composite outcome included kidney failure, sustained decrease of estimated glomerular filtration rate (eGFR) ≥ 40% from baseline over at least 4 weeks, or renal death. The key secondary composite outcome included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: After a median follow-up of 30 months, the finerenone group showed a relative risk reduction (RRR) of 41% (hazard ratio [HR]=0.59, 95% confidence interval [CI], 0.39 to 0.88; p=0.009) for the primary composite outcome compared with placebo, consistent across its components with treatment benefits with finerenone. Based on an absolute between-group difference of 12.2% after 30 months, the number of patients who needed to be treated (NNT) with finerenone to prevent one primary outcome event was eight (95%CI: 4 to 84). For the key secondary composite outcome, the finerenone group showed a RRR of 25% (HR=0.75, 95% CI, 0.38 to 1.48; p=0.408). Adverse events were similar between the two groups. The effects of finerenone on blood pressure were modest. No gynecomastia events were reported in the study. Hyperkalemia leading to discontinuation occurred in eight (4.3%) and two (1.1%) participants in the finerenone and control groups, respectively. The incidence of acute kidney injury was comparable between the two groups (1.6% vs. 1.6%). Conclusions: Finerenone resulted in lower risks of CKD progression than placebo and a balanced safety profile in Chinese patients with CKD and T2DM

TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression

Background: T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 +CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. Methodology: A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. Conclusions: TIM-3 is highly upregulated on both CD4 + and CD8 + TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ + cells were reduced in TIM-3 +CD8 + TILs compared to TIM-3 -CD8 + TILs. However, the level of TIM-3 expression on CD8 + TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3 +CD4 + TILs expressed FOXP3 and about 60% of FOXP3 + TILs were TIM-3 +. Importantly, TIM-3 expression on CD4 + T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells. © 2012 Gao et al

NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR

NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results. Whereas NLRX1 suppressed MAVS-mediated activation of IRF3, it conversely facilitated virus-induced increases in IRF1 expression and thereby enhanced control of viral infection. NLRX1 had a minimal effect on the transcription of IRF1 mediated by the transcription factor NF-kB and regulated the abundance of IRF1 post-transcriptionally by preventing translational shutdown mediated by the double-stranded RNA (dsRNA)-activated kinase PKR and thereby allowed virus-induced increases in the abundance of IRF1 protein