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Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.

Objects: Taurine exhibits protective effects in the context of cardiovascular pathophysiology. A range of evidence suggests that hypertension activates inflammatory responses and oxidative stress in the paraventricular nucleus (PVN), elevating the arterial tone and sympathetic activity, while it induces gut–brain axis dysfunction in the context of hypertension. However, the mechanism underlying taurine's anti-hypertensive effects via the gut–brain axis remains unclear. Method: Male spontaneously hypertensive rats (SHRs) were administered 3% taurine in their drinking water for eight weeks, with their arterial pressure measured weekly. Molecular techniques were employed to investigate taurine's effects on the hypertensive gut and PVN. Additionally, 16S rRNA gene sequencing was used to analyze the gut microbiota composition, and untargeted metabolomics was applied to assess the fecal metabolites following taurine supplementation. Results: Taurine supplementation not only reduced the blood pressure, sympathetic activity, and inflammatory and oxidative stress in the PVN but also improved the cardiac pathology and microbiota composition while alleviating gut inflammation in hypertensive rats. The untargeted metabolite analysis indicated that the primary effect of the taurine intervention in SHRs was exerted on tryptophan metabolism. The levels of serum metabolites such as kynurenine, L-tryptophan, serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) were altered in hypertensive rats following taurine treatment. Conclusions: Taurine supplementation restored the microbiota balance, strengthened the mucosal barrier, reduced intestinal inflammation, and stimulated tryptophan metabolism. The metabolites derived from the gut microbiota likely crossed the brain barrier and reached the paraventricular nucleus, thereby reducing the inflammatory responses and oxidative stress in the PVN via gut–brain communication, leading to decreased sympathetic nerve activity and blood pressure in the studied hypertensive rats. [ABSTRACT FROM AUTHOR]

Five metal nano powders of Fe, Cr, Mn, Ni and Ti were mixed by a planetary ball mill, and then three high entropy alloys of FeCrMnNiTi, FeCrMnNiTi0.5 and FeCrMnNi were prepared by vacuum casting technology. In order to investigate the corrosion behaviors of the three kinds of alloys in NaCl solution, the electrochemical workstation was used to measure the open circuit potential, polarization curve and AC impedance of the three alloys in 3.5%(mass fraction) NaCl solution. Furthermore, the microstructure of the corroded alloy was observed by using a metallurgical microscope and a scanning electron microscope. The electrochemical test results showed that when the self - corrosion potential of FeCrMnNiTi alloy was -0.301 V, the self - corrosion potential of FeCrMnNiTi0.5 alloy was -0.443 V. From the observation of corrosion product morphology, FeCrMnNiTi0.5 was dominated by grain boundary corrosion, and the other two alloys were dominated by pitting corrosion. Overall, FeCrMnNiTi had the best corrosion resistance and FeCrMnNiTi0.5 had the worst corrosion resistance. The addition of Ti might cause the alloy lattice distortion.

From the perspective of national governance, the panel data collected from 30 provinces in China between 2007 and 2019 are used in this paper to empirically test the impact of government audits on green development. Also, multiple models are applied to explore its underlying mechanism from the perspective of innovative activities. The research results show that government audit plays a significant role in promoting green development, which holds even after robustness tests are conducted either by replacing government audit indicators, adopting the GMM system model, applying Heckman's two-stage model, or using micro-enterprise data. From an economic point of view, innovation plays a major part in promoting green development through government audits. There is also a significant trend of regional heterogeneity as shown in the effect of government audits on green development. The promoting effect reaches a more significant extent in the eastern region than in other regions. According to the results of a further expansion analysis, government auditing exerts significant non-linear effects and spatial spillover effects on green development. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: In order to overcome the scarcity and high price of natural cordyceps, the invention replaces the natural cordyceps of Guben Xiaoliu capsule with the cheap and easily obtainable cordyceps mycelium under the condition of keeping the same curative effect. The aim is to provide a kind of Chinese medicine preparation with low price, easy to take, easy to accept for the majority of patients, and at the same time, it is beneficial to ecological protection. Aim of study: The drug components were replaced in Guben Xiaoliu capsule (GBXLC), which has been clinically used for many years in the treatment of lung cancer,and the curative effect was compared. Method: lung cancer mouse models were prepared, which randomly divided into four groups: The normal control group, the model control group, the original GBXLC + cyclophosphamide (CTX) group and the new GBXLC+CTX group, 20 in each group, and began to feed the drug the next day. The two drug groups were added with cyclophosphamide(6 mg/100 g body weight), given by intraperitoneal injection within 48 h after inoculation. The inhibition rate of lung metastasis, tumor Volume and Weight, VEGF and MMP2 expression,tumor microvessel density and the dynamic change of the percentage of Th17/Treg in each group were detected, and The appearance, pathological shape, volume and weight of lung metastases of mice in each group were observed. Results: The appearance, pathological shape, volume and weight of lung metastases of mice in each drug group were better than those in the pathological control group, and there were no significant differences between the drug groups. The VEGF, MMP2, MVD and LVD expressions of both the new GBXLC group and the original GBXLC group were less than those of the model control group (P0.05).The ratio of Thl7/Treg approached normalization in the original GBXLC group and the New Xiaoliu Group,Which means the ratio of Thl7/Treg in the two groups showed no significant difference from that of the normal group. Conclusion: Both the new GBXLC group and the original GBXLC group have good therapeutic effects on lung cancer, and the curative effect is equivalent. Therefore, it is feasible to replace natural Cordyceps sinensis with mycelium of Cordyceps sinensis.

High‐nickel cathode materials are widely used in lithium‐ion batteries because of their advantages of high energy density and high safety. High‐nickel cathode materials need to further improve cycling stability because they are prone to structural changes and capacity degradation. This paper proposes a method to improve high‐nickel cathode materials by Mg doping. XRD proves that Mg‐doped high‐nickel materials still have R‐3 m spatial structural characteristics; Rietveld refinement confirms that the c‐axis gradually increases with the increase of Mg content. Combined with DFT calculations, the presence of Mg can inhibit structural collapse during charge and discharge, reduce Li/Ni antisite defects, improve the electronic conductivity of the material, and improve the cyclic stability of the material. The 0.6 mol % Mg‐doped sample has an initial discharge capacity of 233 mAh g−1 at 0.1 C in the range of 2.7–4.3 V, a capacity retention rate of 91.0 % after 50 cycles at 1 C, still retains 79.9 % after 100 cycles. The dQ/dV curves further indicate that the presence of Mg improves the structural stability of the material. [ABSTRACT FROM AUTHOR]