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It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators. Moreover, IL-7 treatment activates JAK/STAT5 pathway following SCI. At last, more importantly, the pharmacological inhibition of STAT5 abrogates the effects of IL-7 treatment on functional recovery, neuronal apoptosis and focal inflammatory response, suggesting that the effects of IL-7 treatment following SCI are dependent on activating the JAK/STAT5 pathway. Overall, this study reveals the JAK/STAT5 pathway-dependent detrimental role of IL-7 following SCI, and also implies that targeting the IL-7/JAK/STAT5 axis may represent a potential therapeutic approach for SCI treatment. • Intraspinal administration of IL-7 limits functional recovery following SCI. • Intraspinal administration of IL-7 promotes focal inflammatory response. • Intraspinal administration of IL-7 promotes neuronal apoptosis in spinal cord lesions. • Intraspinal administration of IL-7 activates JAK/STAT5 pathway following SCI. [ABSTRACT FROM AUTHOR]

Objective: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. Methods: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO. Wild type male C57BL/6 mice were used as controls (n = 8 per group). After 8 weeks of PIO treatment, we examined the baseline characteristics and metabolic parameters of each group, and we used enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemical staining to evaluate the expression levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), NLRP3, nuclear factor—kappa B (NF-κB), caspase-1, interleukin (IL)-18, and IL-1β in each group. Results: Compared to the diabetic apoE (-/-) group, PIO treatment decreased blood glucose, cholesterol, serum blood urea nitrogen (BUN), and creatinine levels. It also depressed the glomerular mesangial expansion. PIO down-regulated expression of AGEs, RAGE, and NF-κB, all of which further depressed NLRP3, caspase-1, IL-18, and IL-1β levels. Conclusion: Pioglitazone can ameliorate diabetic renal damage, and this effect is related to the inhibition of renal AGE/RAGE axis activation and the down-regulation of NF-κB expression. These effects lead to a decline in NLRP3 levels and downstream secretion of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

The targeting of bacterial type III secretion systems (T3SSs), which are critical virulence factors in most Gram-negative pathogens, is regarded as an alternative strategy for the development of novel anti-microbial drugs. Xanthomonas oryzae pv. oryzae ( Xoo) and X. oryzae pv. oryzicola ( Xoc) are two of the most important bacterial pathogens on rice, which cause leaf blight and leaf streak diseases, respectively. To identify potential anti-virulence drugs against these two pathogens, we screened a library of plant phenolic compounds and derivatives for their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the promoter activity of a harpin gene, hpa1. These inhibitors were further tested for their impact on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results showed that pretreatment of Xoo with TS006 ( o-coumaric acid, OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without affecting bacterial growth or survival. In addition, Cya translocation assays demonstrated that the translocation of two T3 effectors was suppressed by the four inhibitors. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that mRNA levels of representative genes in the hrp ( hypersensitive response and pathogenicity) cluster, as well as the regulatory genes hrpG and hrpX, were reduced by treatment with the four inhibitors, suggesting that expression of the Xoo T3SS was suppressed. The expression of other virulence factors was not suppressed, which indicated possible T3SS-specific inhibition. Finally, we demonstrated that these inhibitors reduced the disease symptoms of Xoo and Xoc on the rice cultivar ( Oryza sativa) IR24 to varying extents. [ABSTRACT FROM AUTHOR]

Deep Neural Networks (DNNs) have developed rapidly in data privacy protection applications such as medical treatment and finance. However, DNNs require high-speed and high-memory computers in terms of computation, otherwise training can be very lengthy. Furthermore, DNNs are often not available in resource-constrained mobile devices. Therefore, training and executing DNNs are increasingly using cloud computing. In the paper, the Power Normalized Cepstrum-based Robust Feature Detector (PNC-RFD), with deep learning in the cloud computing, is proposed for data privacy protection. The proposed PNC-RFD extracts a specified number of signal segments of high robustness used to embed and extract various data. For the sake of embedding and extracting the data, a method of information hiding employing Dual-Tree Complex Wavelet Packet Transform (DT CWPT) is therefore presented. The presented scheme simultaneously embeds multiple data into coefficients of the DT CWPT of signal segments. By embedding the data into the orthogonal spaces, the proposed method ensures the independent extraction of the multiple data. In line with the performance analysis, the superiority of the presented scheme is elaborated through making the comparison with the current state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Abstract: Fish species have poor capability of carbohydrate metabolism relative to mammals. Specifically, fish cannot utilize dietary glucose well. Heat shock protein 72 (Hsp72) can be induced by heat shock and prevent stress-induced activation of c-Jun amino N-terminal kinase (JNK) which then promotes the insulin signaling pathway in mammals. However, the function of Hsp72 on glucose utilization is unknown in fish. We conducted a study to understand the role played by heat shock on glucose utilization using juveniles of the grass carp fish. In this study, the juveniles of grass carp were fed with either high glucose diet or control diet. Half of the juveniles were subjected to several temporary heat shock treatments within 8weeks. The growth performance, body composition of juveniles and the expression of glucose metabolism related genes, including Hsp72 in the livers of juveniles were analyzed from each group. The heat shock treatments could improve growth performance and body composition of grass carp juveniles, and could activate JNK. Though the expression of Hsp72 increased significantly in Group GH (juveniles fed with high-glucose diet and given heat shock treatment) (P <0.05) as measured by fluorescent real time PCR and Western blot, the expression of JNK and p-JNK were not suppressed by Hsp72 in our study, which was different from some previous studies in mammals. In summary, the study showed that heat shock did not affect glucose metabolism through JNK pathway in grass carp. This may give a clue to explain why fish species have a much poorer capability of carbohydrate metabolism than mammals. [Copyright &y& Elsevier]