Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1 ΔHBS , which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1 ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1 WT ) in renal tissues. RNA-seq analysis revealed that FGF1 ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1 ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1 ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3β/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1 ΔHBS . This finding expands the potential uses of FGF1 ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.

To develop novel succinate dehydrogenase inhibitors (SDHIs), two series of novel N-4-fluoro-pyrazol-5-ylbenzamide and N-4-chloro-pyrazol-5-yl-benzamide derivatives were designed and synthesized, and their antifungal activities were evaluated against Valsa mali, Sclerotinia sclerotiorum, FusaHum graminearum Sehw, Physalospora piricola, and Botrytis cinerea. The bioassay results showed that some of the target compounds exhibited good antifungal activities in vitro against V. mali and S. sclerotiorum. Remarkably, compound 9Ip displayed good in vitro activity against V. mali with an EC 50 value of 0.58 mg/L. This outcome was 21-fold greater than that of fluxapyroxad (12.45 mg/L) and close to that of the commercial fungicide tebuconazole (EC 50 = 0.36 mg/L). In addition, in vivo experiments proved that compound 9Ip has good protective fungicidal activity with an inhibitory rate of 93.2% against V. mali at 50 mg/L, which was equivalent to that of the positive control tebuconazole (95.5%). The results of molecular docking indicated that there were obvious hydrogen bonds and p−π interactions between compound 9Ip and succinate dehydrogenase (SDH), which could explain the probable action mechanism. In addition, the SDH enzymatic inhibition assay was carried out to further prove its mode of action. Our studies suggest that compound 9Ip could be a fungicidal lead to discover more potent SDHIs for crop protection.

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The development strategy of the Yangtze River Economic Belt is an important strategy for China to cope with the new normal of economic development. This paper uses provincial panel data from the Information Network of the National Bureau of Statistics of China and the Development Research Centre of the State Council and conduct a panel data fixed effect regression model to empirically study the impact of technological innovation and industrial upgrading on economic development of 11 provinces in the Yangtze River economic belt. The results of full sample estimation show that technological innovation and industrial upgrading can promote economic growth at a significant level of 1%, but the impact of industrial upgrading is not obvious when they are considered separately. According to the results of sub-regional estimation, there is regional heterogeneity in the degree of effect of technological innovation and industrial upgrading on economy. Therefore, the Yangtze River Economic Belt should increase investment in science and technology, adjust industries according to the development orientation of provinces, pay more attention to the rationalization of industrial structure, rationally allocate resources among industries, and pay attention to the complementary development among regions.

Viral diseases are the most common problems threatening human health, livestock, and poultry industries worldwide. Viral infection is a complex and competitive dynamic biological process between a virus and a host/target cell. During viral infection, inflammasomes play important roles in the host and confer defense mechanisms against the virus. Inflammasomes are polymeric protein complexes and are considered important components of the innate immune system. These immune factors recognize the signals of cell damage or pathogenic microbial infection after activation by the canonical pathway or non-canonical pathway and transmit signals to the immune system to initiate the inflammatory responses. However, some viruses inhibit the activation of the inflammasomes in order to replicate and proliferate in the host. In recent years, the role of inflammasome activation and/or inhibition during viral infection has been increasingly recognized. Therefore, in this review, we describe the biological properties of the inflammasome associated with viral infection, discuss the potential mechanisms that activate and/or inhibit NLRP1, NLRP3, and AIM2 inflammasomes by different viruses, and summarize the reciprocal regulatory effects of viral infection on the NLRP3 inflammasome in order to explore the relationship between viral infection and inflammasomes. This review will pave the way for future studies on the activation mechanisms of inflammasomes and provide novel insights for the development of antiviral therapies.

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