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Background and purposeThe kidney is essential in regulating sodium homeostasis and BP. The irreversible oxidation of Cys674 (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) is increased in the renal cortex of hypertensive mice. Whether inactivation of C674 promotes hypertension is unclear. Here we have investigated the effects on BP of the inactivation of C674, and its role in the kidney.Experimental approachWe used heterozygous SERCA2 C674S knock-in (SKI) mice, where half of C674 was substituted by serine, to represent partial irreversible oxidation of C674. The BP, urine volume, and urine composition of SKI mice and their littermate wild-type (WT) mice were measured. The kidneys were collected for cell culture, Na+ /K+ -ATPase activity, protein expression, and immunohistological analysis.Key resultsCompared with WT mice, SKI mice had higher BP, lower urine volume and sodium excretion, up-regulated endoplasmic reticulum (ER) stress markers and soluble epoxide hydrolase (sEH), and down-regulated dopamine D1 receptors in renal cortex and cells from renal proximal tubule. ER stress and sEH were mutually regulated, and both upstream of D1 receptors. Inhibition of ER stress or sEH up-regulated expression of D1 receptors, decreased the activity of Na+ /K+ -ATPase, increased sodium excretion, and lowered BP in SKI mice.Conclusions and implicationsThe inactivation of SERCA2 C674 promotes the development of hypertension by inducing ER stress and sEH. Our study highlights the importance of C674 redox status in BP control and the contribution of SERCA2 to sodium homeostasis and BP in the kidney.

We assess how "implicit" selections based on non-cognitive abilities may have changed in the context of the great higher education expansion in China, applying the classic supply-demand framework and utilizing the Big Five personality model. Using the Chinese General Social Survey (CGSS) data from 2012, difference-in-difference (DID), difference-in-difference-in-difference (DDD) and descriptive analyses establish the following three major findings. First, from the generation entering college before the expansion--post-70s--to the generation entering college after the expansion--post-80s and post-90s--implicit selections in higher education based on personality have weakened with the increased supply of higher education opportunities. Second, selections have significantly weakened in terms of the openness dimension of personality, yet there is some evidence that selections have strengthened in terms of conscientiousness. This reflects that open-mindedness has become a relatively higher supply trait and conscientiousness has become a relatively lower supply trait among members of the post-90s generation. Third, selections have weakened only on the openness dimension for males, but on multiple dimensions beginning with agreeableness for females, reflecting a greatly increased supply of higher education opportunities for females with this dominant trait. The finding on strengthened selections based on conscientiousness has important implications for what and how to educate today's college students.

Since 2000, terrorism in Southeast Asia has developed rapidly via numerous terrorist organizations. As the regional anti-terrorism situation has become increasingly severe, regional security has faced serious challenges. The research is based on the research data of the Global Terrorism Database (GTD), using geospatial statistical methods to visualize the spatial variation terrorist activities in Southeast Asia from 2000 to 2018, and to analyze the characteristics of the temporal and spatial research of terrorist activities in Southeast Asia. Social network analysis methods were used to analyze the internal and external social relations of terrorist organizations in Southeast Asia. This helped us to have a certain understanding of the development situation of terrorism in Southeast Asia and to provide a reference for Southeast Asian countries to formulate relevant counter-terrorism measures and strengthen regional counter-terrorism cooperation in the future. The study draws the following conclusions: (1) A total of 10,440 terrorist activities occurred in Southeast Asia from 2000 to 2018, showing a significant volatility growth over time, with obvious phase changes. According to the trend of terrorism in Southeast Asia and its spatial changes, this period can be divided into three stages, namely: rising volatility (2000-2010), rapid development (2011-2013), and turbulence and change stage (2014-2018). In terms of spatial distribution, Southeast Asian terrorism activities are highly concentrated, with significant agglomeration, showing a trend of diffusion and agglomeration. The agglomeration center has changed from a two-pole agglomeration center in 2000 to a three-level agglomeration center in 2018: the southern region of Thailand, the southern islands of the Philippines and the southern islands of the Philippines, and mountainous areas in western Myanmar. (2) There are many terrorist organizations in Southeast Asia, the types of which are complex. The members of the terrorist organization network are closely related. The terrorist organizations and the lone wolf type terrorism are related through intelligence, resource, and personnel exchanges. A huge cross-regional terrorist organization network has been established. In this network of terrorist organization relations, various terrorist organizations cooperate and act together, posing a serious threat to the anti-terrorism situation in Southeast Asia. In the 1990s, Southeast Asian terrorist organizations represented by JI, established the 4M activity network with a clear division of labor across many countries with the support of foreign organizations and used this activity network to raise funds, train personnel, and plan activities. (3) There are deep-seated reasons for the rapid rise of terrorism in Southeast Asia, not only the influence of social culture, political environment, and economic development within the region but also the intervention of terrorist forces outside the region.

Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial.ObjectiveOur goal was to investigate the mechanisms of endothelial Nox4 in regulating atherosclerosis.Approach and resultsAtherosclerosis-prone conditions (disturbed blood flow, type I diabetes, and Western diet) downregulated endothelial Nox4 mRNA in arteries. To address whether the downregulated endothelial Nox4 was directly involved in the development of atherosclerosis, we generated mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), driven by the endothelial specific promoter Tie-2, on atherosclerosis-prone genetic background (ApoE deficient mice) to mimic the effect of decreased endothelial Nox4. Nox4DN significantly increased type I diabetes-induced aortic stiffness and atherosclerotic lesions. Gene analysis indicated that soluble epoxide hydrolase 2 (sEH) was significantly upregulated in Nox4DN endothelial cells (EC). Inhibition of sEH activity in Nox4DN EC suppressed inflammation and macrophage adhesion to EC. On the contrary, overexpression of endothelial wild type Nox4 suppressed sEH, ameliorated Western diet-induced atherosclerosis and decreased aortic stiffness.ConclusionsAtherosclerosis-prone conditions downregulated endothelial Nox4 to accelerate the progress of atherosclerosis, at least in part, by upregulating sEH to enhance inflammation.

Virtual reality (VR) has sparked substantial interest in language education, but its application in interpreting training is still in its early stages. This review provides the first comprehensive analysis of this emerging field by investigating research trends, study designs, methodological features, key research themes, and major findings. The results indicate a notable rise in research interest, with an increase in publications and a growing diversity of VR platforms being involved. The analysis reveals a shift from design-oriented papers to empirical investigations. The empirical studies primarily employed quantitative or mixed methods analysis, and gathered data through questionnaires, tests, and interviews. Thematic analysis identified four research themes: functionality evaluation and user experience, learning outcomes, platform design and features, and pedagogical and theoretical exploration. Prior studies revealed generally favorable attitudes among users towards the functionality, usability, and immersive learning experiences within VR environments. Additionally, these studies indicated the potential effectiveness of VR in promoting interpreting learning outcomes, as evidenced by self-reported evaluations or comparisons of test results. However, concerns remain regarding technical limitations and learning efficiency. This review highlights the potential for increased use of VR in interpreting training and the need for additional empirical data gathered through enhanced study designs. [ABSTRACT FROM AUTHOR]

Background: Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods: We searched all the relevant studies in PubMed, Embase, and Cochrane Library databases. We also reviewed abstracts of relevant conferences to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results: CRT combined with immunotherapy can improve progression-free survival (PFS) (hazard rate [HR]: 0.60, 95% confidence interval [CI, 0.55–0.60) and overall survival (OS) (HR: 0.59, 95% CI, 0.53–0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5–52.7%) and 71.3% (95% CI, 67.3–75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95% CI, 51.0–70.3%) and 77.4% (95% CI, 73.2–81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95% CI, 31.3–39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95% CI, 31.9–51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95% CI, 5.0–8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95% CI, 3.1–6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95% CI, 2.9–7.3%). Conclusions: Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit. [ABSTRACT FROM AUTHOR]

Objective tumor response after radiotherapy (OR=12.71, 95% CI=3.64– 44.64, P=0.01), and Volume of 200 cGy irradiation (V2) is an independent positive predictor of an increase in CD8+T lymphocyte ratio after radiotherapy (high group, OR=3.40, 95% CI=1.13– 10.36, P=0.03).Conclusion: The increase in CD8+T cells after radiotherapy can positively predict the short-term efficacy of radiotherapy. Mediastinal low-dose radiation therapy can increase CD8+T cells, thereby improving the short-term efficacy of radiotherapy. These potentially related mechanisms are worth further verification and exploration. [ABSTRACT FROM AUTHOR]