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STUDY QUESTION Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? SUMMARY ANSWER Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. WHAT IS KNOWN ALREADY Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited. STUDY DESIGN, SIZE, DURATION We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21–23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21–23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P  < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30–38) than in the control group (35 days, IQR 32–42), with a difference of −1 day (95% CI −2.3 to −0.9; P  = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P  > 0.05). LIMITATIONS, REASONS FOR CAUTION Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P  > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co. Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests. TRIAL REGISTRATION NUMBER CHiCTR2100053565. TRIAL REGISTRATION DATE 24 November 2021. DATE OF FIRST PATIENT'S ENROLMENT 9 March 2022 [ABSTRACT FROM AUTHOR]

Poorly designed internal walls deter natural ventilation of buildings, causing poor indoor air quality and exorbitant energy costs when mechanical ventilation systems are used. Although one can design internal walls with minimum adverse effects on natural ventilation by controlling height, width, location, and porosity of internal walls, less research has been done to date. This study investigated how these four parameters individually and collectively influence the cross-ventilation of buildings using Reynolds-average Navier–Stokes equation-based computational fluid dynamics simulations and the local and global sensitivity analysis. When considering individual parameters, the local sensitivity analysis revealed the positive correlation between internal walls' porosity and cross-ventilation, similar to previous studies. However, the global sensitivity analysis identified the location as the most influential design parameter for cross-ventilation. Furthermore, the global sensitivity analysis revealed nonlinear, non-monotonic, and interactive relations between cross ventilation and all parameters but porosity, highlighting the importance of evaluating all design parameters together and the difficulty in extrapolating the findings for idealized to actual internal wall designs. Based on the findings, this study proposes narrow internal walls with high porosities built away from ventilation openings as a basic internal wall design to maximize the cross-ventilation of buildings. [ABSTRACT FROM AUTHOR]

Effects of three-dimensional (3D) perturbations due to an unstable n = 1 (n is the toroidal mode number) internal kink (IK) on the energetic particles (EPs) are systematically investigated for the HL-2M tokamak, utilizing the MARS-F/K code [Liu et al., Phys. Plasmas 7, 3681–3690 (2000)] and a recently developed test particle tracing module. A high-beta sawteething HL-2M scenario, simulated by the TRANSP code [Breslau et al., Transp Computer Software (2018)], is chosen for this study. In general, the 3D perturbation associated with an unstable IK is found to affect the EP drift orbit, confinement, and loss in HL-2M. The instability-induced EP loss fraction is found to be typically less than 10%, without counting for the prompt orbit loss associated with the 2D equilibrium field for counter-current particles. The latter reaches about 16% in HL-2M. For co-current EPs, a 100 G 3D magnetic field (inside the plasma) due to the IK does not induce any EP loss assuming a static perturbation. A sawtooth-like time-varying perturbation field, with the peak amplitude reaching 1000 G, can however produce about 30% loss for the co-current EPs in HL-2M. The majority of lost EPs tend to strike the lower divertor region, with a small fraction of particles striking the low-field side mid-plane region of the limiting surface. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries (LIBs) are widely used in electrical vehicles (EVs), but safety issues with LIBs still occur frequently. State of charge (SOC) and state of health (SOH) are two crucial parameters for describing the state of LIBs. However, due to inconsistencies that may occur among hundreds to thousands of battery cells connected in series and parallel in the battery pack, these parameters can be difficult to estimate accurately. To address this problem, this paper proposes a joint SOC and SOH estimation method based on the nonlinear state space reconstruction (NSSR) and long short-term memory (LSTM) neural network. An experiment testbed was set up to measure the SOC and SOH of battery packs under different criteria and configurations, and thousands of charging/discharging cycles were recorded. The joint estimation algorithms were validated using testbed data, and the errors for SOC and SOH estimation were found to be within 2.5% and 1.3%, respectively, which is smaller than the errors obtained using traditional Ah-Integral and LSTM-only algorithms. [ABSTRACT FROM AUTHOR]

A systematic investigation is carried out, studying the effect of the neutral beam injection induced energetic particles (EPs) on the n = 1 (n is the toroidal mode number) internal kink (IK) instability in the HL-2M tokamak, utilizing the MARS-F/K code [Liu et al., Phys. Plasmas 7, 3681 (2000) and 15, 112503 (2008)]. A high-beta sawteething HL-2M scenario, simulated by the TRANSP code [Breslau et al. Computer Software (2018)], is chosen for this study. Compared to the fluid model, non-perturbative magnetohydrodynamic (MHD)-kinetic hybrid computations with MARS-K show a generally stabilization effect on the IK, due to drift kinetic resonances associated with EPs. The bounce resonance of trapped EPs has minor influence on the mode stability. In the absence of the plasma equilibrium flow and with the assumed particle pitch distribution, the transit resonance of co-current (countercurrent) passing EPs destabilizes (stabilizes) the IK. With plasma flow, both co- and countercurrent passing EPs tend to stabilize the mode, but the effect is stronger with the countercurrent particles. These modeling results provide useful guidance for interpreting MHD instabilities in the future high-performance experiments in HL-2M. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones’ generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs. [ABSTRACT FROM AUTHOR]

We have studied the molecular mechanism and signal transduction of pim-1, an oncogene encoding a serine-threonine kinase. This is a true oncogene which prolongs survival and inhibits apoptosis of hematopoietic cells. In order to determine whether the effects of Pim-1 occur by regulation of the mitogen-activated protein kinase pathway, we used a transcriptional reporter assay by transient co-transfection as a screening method. In this study, we found that Pim-1 inhibited the Elk-1 and NFkappaB transcriptional activities induced by activation of the mitogen-activated protein kinase cascade in reporter gene assays. However, Western blots showed that the induction of Elk-1-regulated expression of endogenous c-Fos was not affected by Pim-1. The phosphorylation and activation of neither Erk1/2 nor Elk-1 was influenced by Pim-1. Also, in the gel shift assay, the pattern of endogenous NFkappaB binding to its probe was not changed in any manner by Pim-1. These data indicate that Pim-1 does not regulate the activation of Erk1/2, Elk-1 or NFkappaB. These contrasting results suggest a pitfall of the transient co-transfection reporter assay in analyzing the regulation of transcription factors outside of the chromosome context. It ensures that results from reporter gene expression assay should be verified by study of endogenous gene expression.