H2S is involved in drought-mediated stomatal closure through PLDα1 in Arabidopsis.

MAIN CONCLUSION: PLDα1 promoted H2S production by positively regulating the expression of LCD. Stomatal closure promoted by PLDα1 required the accumulation of H2S under drought stress. Phospholipase Dα1 (PLDα1) acting as one of the signal enzymes can respond to drought stress. It is well known that hydrogen sulfide (H2S) plays an important role in plant responding to biotic or abiotic stress. In this study, the functions and relationship between PLDα1 and H2S in drought stress resistance in Arabidopsis were explored. Our results indicated that drought stress promotes PLDα1 and H2S production by inducing the expression of PLDα1 and LCD genes. PLDα1 and LCD enhanced plant tolerance to drought by regulating membrane lipid peroxidation, proline accumulation, H2O2 content and stomatal closure. Under drought stress, the H2O2 content of PLDα1-deficient mutant (pldα1), L-cysteine desulfhydrase (LCD)-deficient mutant (lcd) was higher than that of ecotype (WT), the stomatal aperture of pldα1 and lcd was larger than that of WT. The transcriptional and translational levels of LCD were lower in pldα1 than that in WT. Exogenous application of the H2S donor NaHS or GYY reduced the stomatal aperture of WT, pldα1, PLDα1-CO, and PLDα1-OE lines, while exogenous application of the H2S scavenger hypotaurine (HT) increased the stomatal aperture. qRT-PCR analysis of stomatal movement-related genes showed that the expression of CAX1, ABCG5, SCAB1, and SLAC1 genes in pldα1 and lcd were down-regulated, while ACA1 and OST1 gene expression was significantly up-regulated. Thus, PLDα1 and LCD are required for stomatal closure to improve drought stress tolerance.

Heme Oxygenase-1 Gene (GT)n Polymorphism Linked to Deep White Matter Hyperintensities, Not Periventricular Hyperintensities.

BACKGROUND: Oxidative stress plays a principal role in the pathogenesis of white matter hyperintensities (WMHs). The induction of heme oxygenase-1 (HO-1) gene in the brain represents 1 of the pivotal mechanisms to counteract the noxious effects of reactive oxygen species, and the transcriptional modulation of HO-1 induction depends on the length of a GT-repeat (GT)n in the promoter region. We investigated whether the HO-1 gene (GT)n polymorphism is associated with the risk of WMHs. METHODS AND RESULTS: A total of 849 subjects from the memory clinic were consecutively enrolled, and the HO-1 (GT)n genotype was determined. WMHs were assessed with the Fazekas scale and further divided into periventricular WMHs and deep WMHs (DWMHs). Allelic HO-1 (GT)n polymorphisms were classified as short (≤24 (GT)n), median (25≤[GT]n<31), or long (31≤[GT]n). Multivariate logistic regression analysis was used to evaluate the effect of the HO-1 (GT)n variants on WMHs. The number of repetitions of the HO-1 gene (GT)n ranged from 15 to 39 with a bimodal distribution at lengths 23 and 30. The proportion of S/S genotypes was higher for moderate/severe DWMHs than none/mild DWMHs (22.22% versus 12.44%; P=0.001), but the association for periventricular WMHs was not statistically significant. Logistic regression suggested that the S/S genotype was significantly associated with moderate/severe DWMHs (S/S versus non-S/S: odds ratio, 2.001 [95% CI, 1.323-3.027]; P<0.001). The HO-1 gene (GT)n S/S genotype and aging synergistically contributed to the progression of DWMHs (relative excess risk attributable to interaction, 6.032 [95% CI, 0.149-11.915]). CONCLUSIONS: Short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from DWMHs, but not periventricular WMHs. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100045869.

Coping with Coronavirus Pandemic: Risk Perception Predicts Life Optimism.

Given that the coronavirus pandemic has become a severe concern worldwide, how can optimism be maintained during an outbreak of a collective pandemic? We propose that perceived control and negative affect could be potential explanatory factors for optimism in the face of a pandemic. In Study 1 (N = 599), through a large-scale cross-sectional design, we showed the indirect effect of risk perception on optimism through perceived control and negative affect with structural equation modeling. In Study 2 (N = 191), we manipulated perceived risk of the pandemic and determined that experiencing a high-risk pandemic psychologically led to decreased optimism. Finally, through Study 3 (N = 186) and Study 4 (N = 217), we revealed that the effect of risk perception on optimism can be extended to overall subjective well-being and confirmed the indirect effects via perceived control and negative affect. These findings indicate that risk perception can make a difference in one's life optimism during a high-risk pandemic. Moreover, perceived control and negative affect are notable intermediary variables. Measures that strengthen publicity and transparency regarding recovery rates should be taken to help reduce public perceptions of risk and promote an optimistic life attitude.

Hemiasterlin derivative (R)(S)(S)-BF65 and Akt inhibitor MK-2206 synergistically inhibit SKOV3 ovarian cancer cell growth.

We reported previously that a hemiasterlin derivative BF65 is a potent anticancer agent that can inhibit microtubule assembly. Here we show that a more potent stereospecific diastereomer (R)(S)(S)-BF65 can synergize with an allosteric Akt inhibitor MK-2206 to suppress the growth of SKOV3 ovarian cancer cells with constitutively active Akt. (R)(S)(S)-BF65 induced mitotic arrest and MK-2206 caused G0/G1 arrest, while the combination of both induced simultaneous G0/G1 and G2/M cell cycle arrest. (R)(S)(S)-BF65 induced phosphorylation and inactivation of Bcl-2, and downregulated Mcl-1, consequently may lead to apoptosis. (R)(S)(S)-BF65 inhibited mitogen-activated protein kinases (MAPKs), which may stimulate cell proliferation upon activation. (R)(S)(S)-BF65 also induced DNA damage after long-term treatment. MK-2206 is known to inhibit phosphorylation and activation of Akt and suppress cancer cell growth. The combination of (R)(S)(S)-BF65 and MK-2206 also inhibited the Akt pathway. Interestingly, MK-2206 upregulated Bcl-2 and induced activation of MAPKs in SKOV3 cells; however, when combined with (R)(S)(S)-BF65, these prosurvival effects were reversed. The combination also more significantly decreased Mcl-1 protein, increased PARP cleavage, and induced γ-H2AX, a DNA damage marker. Remarkably, MK-2206 enhanced the microtubule depolymerization effect of (R)(S)(S)-BF65. The combination of (R)(S)(S)-BF65 and MK-2206 also markedly inhibited cell migration. Thus, MK-2206 synergizes with (R)(S)(S)-BF65 to inhibit SKOV3 cell growth via downregulating the Akt signaling pathway, and enhancing the microtubule disruption effect of (R)(S)(S)-BF65. (R)(S)(S)-BF65 in turn suppresses Bcl-2 and MAPKs induced by MK-2206. (R)(S)(S)-BF65 and MK-2206 compensate each other leading to increased apoptosis and enhanced cytotoxicity, and may also suppress cancer cell invasion.

Team innovation climate and knowledge sharing among healthcare managers: mediating effects of altruistic intentions.

BACKGROUND: This paper aims to provide empirical evidence concerning the impact of team climate on knowledge sharing behavior and the mediating effects of individuals' altruistic intentions in the context of healthcare settings. METHODS: Questionnaire data were collected from 212 administrators employed at a medical center in Taiwan. Team climate was assessed by the Team Climate Inventory composed of four factors, participative safety, support for innovation, vision, and task orientation. The proposed hypotheses were tested using structural equation modeling. RESULTS: The influence of the team innovation climate on knowledge sharing behavior was evident. Furthermore, individuals' altruistic intentions played a full mediating role in the relationship between team innovation climate and knowledge sharing behavior. CONCLUSIONS: These results contribute to the field of the people-orientated perspective in knowledge management. The full mediating effect of employees' altruistic intentions provides healthcare team managers the direction to accelerate knowledge sharing behavior.