Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control

According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).

Investigation of low-cycle fatigue behavior of austenitic stainless steel for cold-stretched pressure vessels

Cold-stretched pressure vessels from austenitic stainless steels （ASS） are widely used for storage and transportation of liquefied gases, and have such advantages as thin wall and light weight. Fatigue is an important concern in these pressure vessels, which are subjected to alternative loads. Even though several codes and standards have guidelines on these pressure vessels, there are no relevant design methods on fatigue failure. To understand the fatigue properties of ASS 1.4301 （equivalents include UNS $30400 and AISI 304） in solution-annealed （SA） and cold-stretched conditions （9% strain level） and the response of fatigue properties to cold stretching （CS）, low-cycle fatigue （LCF） tests were performed at room temperature, with total strain amplitudes ranging from ：~0.4% to ＂0.8%. Martensite transformations were measured during the tests. Comparisons on cyclic stress response, cyclic stress-strain behavior, and fatigue life were carried out between SA and CS materials. Results show that CS reduces the initial hardening stage, but prolongs the softening period in the cyclic stress response. Martensite transformation helps form a stable regime and subsequent secondary hardening. The stresses of monotonic and cyclic stress-strain curves are improved by CS, which leads to a lower plastic strain and a much higher elastic strain. The fatigue resistance of the CS material is better than that of the SA material, which is approximately 1 - 103 to 2 - 104 cycles. The S-N curve of the ASME standard for ASS is compared with the fatigue data and is justified to be suitable for the fatigue design of cold-stretched pressure vessels. However, considering the CS material has a better fatigue resistance, the S-N curve will be more conservative. The present study would be helpful in making full use of the advantages of CS to develop a new S-N curve for fatigue design of cold-stretched pressure vessels.

Small RNAs in regulating temperature stress response in plants

Due to global climate change, temperature stress has become one of the primary causes of crop losses worldwide. Much progress has been made in unraveling the complex stress response mechanisms in plants, particularly in the identification of temperature stress responsive protein-coding genes. Recently discovered micro RNAs(mi RNAs) and endogenous small-interfering RNAs(si RNAs) have also been demonstrated as simportant players in plant temperature stress response.Using high-throughput sequencing, many small RNAs,especially mi RNAs, have been identified to be triggered by cold or heat. Subsequently, several studies have shown an important functional role for these small RNAs in cold or heat tolerance. These findings greatly broaden our understanding of endogenous small RNAs in plant stress response control. Here, we highlight new findings regarding the roles of mi RNAs and si RNAs in plant temperature stress response and acclimation. We also review the current understanding of the regulatory mechanisms of small RNAs in temperature stress response, and explore the outlook for the use of these small RNAs in molecular breeding for improvement of temperature stress tolerance in plants.