The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization.

The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO2)-induced vasodilation. We showed that SO2 induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted rat aortic rings in association with an increase in cGMP concentration, whereas l-aspartic acid ß-hydroxamate (HDX), an inhibitor of SO2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 µM) attenuated the vasodilatory effects of SO2, suggesting the involvement of cGMP pathway in SO2-induced vasodilation. Mechanistically, SO2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2 exerted its vasodilatory effects at least partly by promoting disulfide-dependent dimerization of sGC and PKG, resulting in an activated sGC/cGMP/PKG pathway in blood vessels. These findings revealed a new mode of action and mechanisms by which SO2 regulated the vascular tone.

Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats.

BACKGROUND: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats. METHODS: High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine ß-lyase (CBS), cystathionine γ-lyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested. RESULTS: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1α was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt. CONCLUSIONS: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.

A pathway towards high-quality development of the manufacturing industry: Does scientific and technological talent matter?

Against the background of the accelerated evolution of the new round of scientific and technological revolution and industrial change, scientific and technical talents, as essential innovation resources, play an important role in promoting the high-quality development of the manufacturing industry. Based on the panel data of 30 provinces in China from 2012 to 2021, the article constructs a fixed-effects model and systematically researches the impact of scientific and technological talents on the high-quality development of the manufacturing industry. The results show that scientific and technical talents play a significant role in promoting the high-quality development of the manufacturing industry, and the upgrading of the consumption structure and the accumulation of productive service industries play a mediating role. Heterogeneity analysis found that the promotion effect of scientific and technical talents is more favorable in the eastern region, medium-technology level manufacturing, and labor-intensive manufacturing. Among the three sub-dimensions of scientific and technological talents, the scale of scientific and technical talents has the most significant impact on the development of the manufacturing industry. The analysis of the spatial spillover effect finds that scientific and technological talents will have a positive spillover effect on the development of the manufacturing industry in neighboring areas. The study provides a basis for relevant departments to formulate effective strategies and policies.

Characterization of the complete mitochondrial genome of Gymnosoma dolycoridis (Diptera, Tachinidae) and phylogenetic analysis.

The complete mitogenome of Gymnosoma dolycoridis Dupuis, 1960 was determined in this study. It is 15,185 bp in length, consisting of 13 protein-coding genes (PCG), 22 transfer RNA genes, two ribosomal RNA genes and one non-coding control region. The A + T content of the mitogenome is 78.5%. A maximum-likelihood phylogenetic tree built on 13 PCGs of 15 tachinid species indicated that Gymnosoma dolycoridis is clustered with other members of the subfamily Phasiinae as conventional taxonomy predicted.

Identification of the Pathogen Causing Leaf Spot in Zinnia elegans and Its Sensitivity to Five Fungicides.

Zinnia elegans Jacq. is an important, globally cultivated ornamental plant. In August 2021, a leaf spot disease was observed in zinnia in Shibing County, Guizhou, China, with an incidence of approximately 60%. Pathogens were isolated and purified from the infected leaves by tissue isolation, and pathogen strain BRJ2 was confirmed as the pathogen causing the leaf spot. Based on morphology and ITS, TEF-1α, and TUB2 sequence analyses, the pathogen was identified as Nigrospora musae (McLennan and Hoëtte). The mycelial growth rate method was used to determine the in vitro toxicity of five fungicides to the pathogen. The results showed that 10% difenoconazole provided the strongest inhibitory effect on N. musae, with a concentration for 50% of maximal effect (EC50) of 0.0658 mg/L; 75% trifloxystrobin·tebuconazole had the second greatest effect, with an EC50 of 0.1802 mg/L. This study provides the first report that N. musae caused leaf spot disease in Z. elegans and provides important guidance for the effective prevention and control of this disease in Guizhou.

Sulfhydration-associated phosphodiesterase 5A dimerization mediates vasorelaxant effect of hydrogen sulfide.

The study was designed to examine if the vasorelaxant effect of hydrogen sulfide was mediated by sulfhydration-associated phosphodiesterase (PDE) 5A dimerization. The thoracic aorta of rat was separated and the vasorelaxant effects were examined with in vitro vascular perfusion experiments. The dimerization and sulfhydration of PDE 5A and soluble guanylatecyclase (sGC) were measured. PDE 5A and protein kinase G (PKG) activities were tested. Intracellular cGMP content was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that NaHS relaxed isolated rat vessel rings at an EC50 of (1.79 ± 0.31)×10-5mol/L, associated with significantly increased PKG activity and cGMP content in vascular tissues. Sulfhydration of sGC ß1 was increased, while the levels of sGC αß1 dimers were apparently decreased after incubation with NaHS in vascular tissues. Moreover, PDE 5A homodimers were markedly decreased, and accordingly the PDE 5A activity demonstrated by the content of 5'-GMP was significantly decreased after incubation with NaHS or GYY4137. Mechanistically, both NaHS and GYY4137 significantly enhanced the PDE 5A sulfhydration in vascular tissues. DTT partially abolished the effects of NaHS on PDE 5A activity, cGMP content and vasorelaxation. Therefore, the present study for the first time suggested that H2S exerted vasorelaxant effect probably via sulfhydration-associated PDE 5A dimerization.