Mechanical performance of 22SiMn2TiB steel welded with low-transformation-temperature filler wire and stainless steel filler wire

TX-80 low-transformation-temperature (LTT) welding wire was used to replace the traditional ER 307Si welding wire to realize the connection of 22SiMn2TiB armor steel in manual overlay welding. The previously existing issues, such as welding cracks, large welding deformation, and severe welding residual stress, were solved to ensure good strength and ductility requirements. In particular, with the same welding conditions, TX-80 LTT wire eliminates welding cracks. It reduces the welding deformation no matter the base pretreatment of pre-setting angle or no pre-setting angle. By comparison, it was found that the microstructure at the TX-80 weld is mainly composed of martensite and a small amount of retained austenite. In contrast, the microstructure of the ER 307Si weld consists of a large amount of austenite and a small amount of skeleton-like ferrite. The variation trend of residual stress and microhardness from the weld to the base were investigated and compared with the mechanical properties of base materials. The TX-80 and the ER 307Si tensile samples elongation is 6.76% and 6.01%, while the ultimate tensile strengths are 877 and 667 MPa, respectively. The average impact toughness at room temperature of the ER 307Si weld is 143.9 J/cm2, much higher than that of the TX-80 weld, which is only 36.7 J/cm2. The relationship between impact and tensile properties with microstructure species and distribution was established. In addition, the fracture surface of the tensile and the impact samples was observed and analyzed. Deeper dimples, fewer pores, larger radiation zone, and shear lips of TX-80 samples indicate better tensile ductility and worse impact toughness than those of ER 307Si weld.</p

Effect of Lycii fructus polysaccharides on ovulation failure in rats

Purpose: To investigate the effect of Lycii Fructus polysaccharides (LFPS) on ovulation failure.Methods: A rat model of ovulation failure was established by intragastric administration of hydroxyurea (300 mg/kg). Rats with ovulation failure then received LFPS via oral administration at doses of 100, 200, or 400 mg/kg. The body, uterus and ovary of each rat were weighed using electronic scales. The hypothalamic-pituitary-ovarian (HPO) axis hormones, including estradiol (E2) level, follicle-stimulating hormone (FSH) activity, and luteinizing hormone (LH) activity in the serum of each rat were determined by enzyme-linked immunosorbent assay (ELISA). The levels of pro-apoptotic proteins (Fas, FasL, FADD, c-caspase-8, c-caspase-10, c-caspase-3, c-caspase-6, and c-caspase-7) in the ovarian tissue of each rat were detected by western blot.Results: Hydroxyurea reduced significantly (p &lt; 0.01) uterus and ovary indices (uterus or ovary weight/body weight) (0.119 and 0.026 %), E2 level (3.42 pmol/L), and FSH and LH activities (2.28 and 2.76 U/L), compared with those in the normal group (0.169 and 0.039 %; 6.72 pmol/L; 2.76 and 3.75 U/L). Hydroxyurea increased significantly (p &lt; 0.01) the levels of the above-mentioned pro-apoptotic proteins relative to those in the normal group. LFPS (100, 200, or 400 mg/kg) reversed significantly (p &lt; 0.05 or 0.01) the effect of hydroxyurea on all of the above indices.Conclusion: LFPS exhibits a protective effect on hydroxyurea-induced ovulation failure by regulating the HPO axis hormones and death receptor-mediated apoptotic pathway.Keywords: Lycii Fructus polysaccharides, Ovulation failure, Hypothalamic-pituitary-ovarian axis, Death receptor-mediated apoptotic pathwa

Probability or time: Effect of presentation format on continuous risky decisions

Continuous risky decisions refer to decisions that involve trade-offs among options with persistent risks. People can use the probability of occurrence per unit time (e.g., ‘the probability of occurrence is 1% per month’) or the average time of risk occurrence (e.g., ‘the average occurrence time is 100 months’) to represent continuous risky options. In this study, we examined the effect of the presentation format (i.e., the probability of occurrence per unit time vs. the average time of risk occurrence) on continuous risky decisions in the gain domain and further explored the underlying mechanism. In Study 1 (N = 122), we demonstrated the effect of presentation format on continuous risky decisions and the moderating effect of the magnitude of probabilities. Specifically, when the probabilities were relatively low, compared with the probability of occurrence per unit time, using the average time of risk occurrence to present the continuous risky options led to more risk-averse decisions. However, when the probabilities were relatively high, compared with the probability of occurrence per unit time, the presentation format of the average time occurrence led to more risk-seeking decisions. In Study 2 (N = 136), we found that the moderating effect of the option probabilities on continuous risky decisions was mediated by the subjective attribute-wise difference judgment. In Study 3 (N = 221), we replicated the effect of presentation format on continuous risky decisions in more natural scenarios. The study offered a deep understanding of the mechanism of continuous risky decision-making, and the results were conducive to further developing theories in relevant fields

Multiple functional neurosteroid binding sites on GABAA receptors

Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While gamma amino-butyric acid Type A (GABAA) receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry (MS), we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human α1β3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the α1 (labeled residues α1-N408, Y415) and β3 (labeled residue β3-Y442) subunits, adjacent to the extracellular domains (ECDs). An intersubunit site (labeled residues β3-L294 and G308) in the interface between the β3(+) and α1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies of receptors with mutations based on these predictions (α1-V227W, N408A/Y411F, and Q242L) indicate that both the α1 intrasubunit and β3-α1 intersubunit sites are critical for neurosteroid action

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway

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.</p