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Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum. Reactive oxygen species (ROS) elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles, while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing (POA), which might be related to the activation of cellular endogenous antioxidant system. All these defects could be rescued by ketone body administration, which suppressed ROS-activated follicle apoptosis. Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.

SummaryEmbryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

Gonadal white adipose tissue (gWAT) can regulate gametogenesis via modulation of neuroendocrine signaling. However, the effect of gWAT on the local microenvironment of the gonad was largely unknown. Herein, we ruled out that gWAT had a neuroendocrine effect on gonad function through a unilateral lipectomy strategy, in which cutting off epididymal white adipose tissue could reduce seminiferous tubule thickness and decrease sperm counts only in the adjacent testis and epididymis of the affected gonad. Consistent with the results in males, in females, ovary mass was similarly decreased by lipectomy. We determined that the defects in spermatogenesis were mainly caused by augmented apoptosis and decreased proliferation of germ cells. Transcriptome analysis suggested that lipectomy could disrupt immune privilege and activate immune responses in both the testis and ovary on the side of the lipectomy. In addition, lipidomics analysis in the testis showed that the levels of lipid metabolites such as free carnitine were elevated, whereas the levels of glycerophospholipids such as phosphatidylcholines and phosphatidylethanolamines were decreased, which indicated that the metabolic niche was also altered. Finally, we show that supplementation of phosphatidylcholine and phosphatidylethanolamine could partially rescue the observed phenotype. Collectively, our findings suggest that gWAT is important for gonad function by not only affecting whole-body homeostasis but also via maintaining local metabolic and immune niches.

Background: COVID-19 is a global epidemic posing threat to public health. Without specific drugs and therapies, it is important to evaluate the effectiveness of currently applicable drugs.This study was a retrospective analysis of the effect of the administration of statins on survival in patients with severe COVID-19.Design: This study was a retrospective analysis of data collected in the ICU of Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology (HUST) during the COVID-19 outbreak.Data from69 patients with severe COVID-19 treated in the ICU from February to March 2020 were collected for the analysis.Patients with severe COVID-19 were treated with the standard of care at the time, and some patients were also treated with statins.Results: Sixty-four patients with complete records were enrolled in the final stage of analysis. Statin administration had a beneficial effect on the overall survival of the patients. The statin administration cohorthad a significantly shorter activated partial thromboplastin time (aPTT) and prothrombin time (PT) according to t-tests. The aPTT and PT were also stable, as shown by locally weighted smoothing (LOESS) analysis. The use of statins combined with corticosteroids, anti-coagulants and anti-hypertensive drugs had a relatively greater effect on survival.Conclusions: Statins can be therapeutic agents that may promote patient survival, possibly by improving coagulation function. Trial registration: HIRB 2020-1119 September 11th, 2020, retrospectively registered.

In this study, we develop a rapid detection system to assess the heart valve function. This system uses a sphygmomanometer combined with temperature and pulse sensing system. By this system, the initial diagnosis can be carried out quickly. This system uses Labview as development environment to design the human-machine interface. By pressurization and pressure relief on arm, the temperature of Peripheral-limb will change. Finally, basing on the test results to analyze the temperature curve, it shows that there is approximately 3°C to 4.5°C temperature difference.

The simulation of the interaction between steel caternary risers (SCRs) and seabed was studied based on beam on elastic foundation theory and the node-spring system foundation mehod for comparison, with the SCR modeled by extensible flexibility cable curve beam. Not only the bottom support and the friction forces were taken into account, but also the damping force of seabed was included in the model of the interaction between SCR and seabed. The results show that compared with using the node-spring system foundation, the effect of the element length of the model on analytical result is insignificant and a longer element could be used for the model, when the beam on elastic foundation model is used. So, the analysis is not time-consuming and the memory requirement is not so large by using the beam on elastic foundation model.