Numerical investigation on the cavitating wake flow around a cylinder based on proper orthogonal decomposition

The non-cavitating and cavitating wake flow of a circular cylinder, which contains multiscale vortices, is numerically investigated by Large Eddy Simulation combined with the Schnerr–Sauer cavitation model in this paper. In order to investigate the spatiotemporal evolution of cavitation vortex structures, the Proper Orthogonal Decomposition (POD) method is employed to perform spatiotemporal decomposition on the cylinder wake flow field obtained by numerical simulation. The results reveal that the low-order Proper Orthogonal Decomposition modes correspond to large-scale flow structures with relatively high energy and predominantly single frequencies in both non-cavitating and cavitating conditions. The presence of cavitation bubbles in the flow field leads to a more pronounced deformation of the vortex structures in the low-order modes compared to the non-cavitating case. The dissipation of pressure energy in the cylinder non-cavitating wake occurs faster than the kinetic energy. While in the cavitating wake, the kinetic energy dissipates more rapidly than the pressure energy

Numerical investigation of energy loss distribution in the cavitating wake flow around a cylinder using entropy production method

The wake flow of a circular cylinder is numerically investigated by Large Eddy Simulation (LES) combined with the Schnerr–Sauer cavitation model. By comparing entropy production in the presence or absence of cavitation, the energy loss distribution in the wake flow field of a cylinder is explored, shedding light on the interactions between multiscale vortex systems and cavitation. The comparative results reveal that, under non-cavitating conditions, the energy loss region in the near-wake area is more concentrated and relatively larger. Energy dissipation in the wake flow field occurs in regions characterized by very high velocity gradients, primarily near the upper and lower surfaces of the cylinder near the leading edge. The influence of cavitation bubbles on entropy production is predominantly observed in the trailing-edge region (W1) and the near-wake region (W2). The distribution trends of wall entropy production on the cylinder’s surface are generally consistent in both conditions, with wall entropy production primarily concentrated in regions exhibiting high velocity gradients

Effects of the Zishen Yutai Pill compared with placebo on pregnancy outcomes among women in a fresh embryo transfer cycle: a Post Hoc subgroup analysis of a randomized controlled trial

ObjectiveTo assess whether the administration of Zishen Yutai Pill (ZYP) could improve the pregnancy outcomes in different subgroups of women undergoing fresh embryo transfer cycles.Materials and methodsThis is a post hoc analysis of a large scale, placebo-controlled, double blind, randomized clinical trial (RCT) regarding the use of ZYP during assisted reproductive technology (ART) treatment. The RCT was conducted at 19 in vitro fertilization (IVF) centers between April 2014 and June 2017. A total of 2265 women undergoing fresh embryo transfer cycles were randomly assigned in a 1:1 ratio to receive ZYP (n = 1131) or placebo (n = 1134). Post hoc logistic regression analyses were applied in this study to examine the between-group differences of ZYP and placebo on clinical pregnancy rate among different subgroups. Detailed analyses, both in intention-to-treat (ITT) and per-protocol population, were also conducted in specific subgroups with regards to rates of implantation, biochemical pregnancy, clinical pregnancy, live birth, pregnancy loss, as well as other neonatal indices.ResultsZYP showed a significantly higher clinical pregnancy rates than placebo in the ITT population. Detailed subgroup analyses were conducted in subgroup in advanced maternal age (AMA, ≥ 35 years old) and overweight/obese patients (BMI > 24), due to the clinical importance and statistical results. In these subgroups, baseline characteristics were similar between two arms (all P > 0.05). Significantly elevated clinical pregnancy rates were observed in ZYP cohort (both P < 0.05) compared with the placebo group. Results also showed that ZYP treatment resulted in significantly higher rates of implantation, biochemical pregnancy in AMA or overweight/obese patients in ITT analysis (all P < 0.05).ConclusionsThe current post hoc subgroup analysis suggested that AMA and overweight/obese women could experience clinical benefits when treated with ZYP in their fresh embryo transfer cycles. The study provides references for the use of ZYP in ART practices. However, further studies in specific subgroups should be examined in more rigorous clinical trial settings.Clinical trial registrationChictr.org.cn, ChictrTRC-14004494

SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense

Abstract Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose‐6‐phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH‐producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS. SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5‐dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation

WT1 Recruits TET2 to Regulate Its Target Gene Expression and Suppress Leukemia Cell Proliferation

The TET2 DNA dioxygenase regulates cell identity and suppresses tumorigenesis by modulating DNA methylation and expression of a large number of genes. How TET2, like most other chromatin modifying enzymes, is recruited to specific genomic sites is unknown. Here we report that WT1, a sequence-specific transcription factor, is mutated in a mutually exclusive manner with TET2, IDH1 and IDH2 in acute myeloid leukemia (AML). WT1 physically interacts with and recruits TET2 to its target genes to activate their expression. The interaction between WT1 and TET2 is disrupted by multiple AML-derived TET2 mutations. TET2 suppresses leukemia cell proliferation and colony formation in a manner dependent on WT1. These results provide a mechanism for targeting TET2 to specific DNA sequence in the genome. Our results also provide an explanation for the mutual exclusivity of WT1 and TET2 mutations in AML and suggest an IDH1/2-TET2-WT1 pathway in suppressing AML

Efficacy and safety of microwave ablation for benign breast lesions: a systematic review and meta-analysis

AIM: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of microwave ablation (MWA) for benign breast lesions. MATERIAL AND METHODS: PubMed, Embase, Web of Science, Cochrane Library databases, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform databases were searched. RESULTS: A total of 10 studies were included, giving a sample size of 1241 patients and 2729 benign breast lesions. The first complete ablation success rate was 96%. The volume reduction ratio (VRR) after 3/6/12 months was 47.4%, 62.1%, and 85.8%, respectively. After 12 months, the lesion disappearance rate was 53.6%, and the efficiency rate was 99%. The rate of excellent cosmesis was 88% and the rate of good cosmesis was 10%. The complication rate was 2%. CONCLUSIONS: MWA is safe and effective for treating benign breast lesions. It can be a promising minimally invasive choice for benign breast lesions

Regulatory effects of Zishen Yutai Pill on endometrial epithelial response in vitro in immunology microenvironment

Objective: Zishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women’s health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB). Results: Compared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P < 0.05). Up-regulation of ICAM-1 expression after treatment of ZYP was further confirmed by WB analysis. Conclusion: In brief, in the presence of uNK cell medium, ZYP could improve the expressions of ICAM1, CSF1, CSF2, TNF, SPP1, etc. However, further exploration should be carried out in in vivo experiments for the validation of the mechanisms of ZYP on endometrial epithelial response

Correction: Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1.

[This corrects the article DOI: 10.1371/journal.pbio.1002243.]

Mitochondrial glycerol 3-phosphate dehydrogenase deficiency exacerbates lipotoxic cardiomyopathy

Summary: Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes