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Abstract With an aging population seeking infertility treatment, diminished ovarian reserve (DOR) is a prevalent indication for assisted reproductive technology (ART). This study aims to investigate the relationship between sleep parameters and DOR among women attending an infertility clinic. Methods We consecutively enrolled women attending an infertility clinic from July 2020 to June 2021. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale(ESS), and STOP-Bang Questionnaire to assess self-reported sleep quality. DOR-related indices including antral follicle count, anti-Müllerian hormone(AMH), follicle-stimulating hormone (FSH) were evaluated. A total of 979 women were enrolled, with 148 classified into the DOR group and 831 in the non-DOR group. The DOR group was notably older compared to the non-DOR group. Analysis showed that the DOR group exhibited significantly shorter sleep onset latency (p = 0.001) and shorter total sleep duration (p = 0.014) compared to the non-DOR group. Logistic regression analysis identified age, PSQI-sleep latency, and PSQI score as independent factors associated with an increased risk of DOR(all p

Electrical manipulation of magnetization without an external magnetic field is critical for the development of advanced non-volatile magnetic-memory technology that can achieve high memory density and low energy consumption. Several recent studies have revealed efficient out-of-plane spin-orbit torques (SOTs) in a variety of materials for field-free type-z SOT switching. Here, we report on the corresponding type-x configuration, showing significant in-plane unconventional spin polarizations from sputtered ultrathin [Pt/Co]N, which are either highly textured on single crystalline MgO substrates or randomly textured on SiO2 coated Si substrates. The unconventional spin currents generated in the low-dimensional Co films result from the strong orbital magnetic moment, which has been observed by X-ray magnetic circular dichroism (XMCD) measurement. The x-polarized spin torque efficiency reaches up to -0.083 and favors complete field-free switching of CoFeB magnetized along the in-plane charge current direction. Micromagnetic simulations additionally demonstrate its lower switching current than type-y switching, especially in narrow current pulses. Our work provides additional pathways for electrical manipulation of spintronic devices in the pursuit of high-speed, high-density, and low-energy non-volatile memory.

While magnetoresistive random-access memory (MRAM) stands out as a leading candidate for embedded nonvolatile memory and last-level cache applications, its endurance is compromised by substantial self-heating due to the high programming current density. The effect of self-heating on the endurance of the magnetic tunnel junction (MTJ) has primarily been studied in spin-transfer torque (STT)-MRAM. Here, we analyze the transient temperature response of two-terminal spin–orbit torque (SOT)-MRAM with a 1 ns switching current pulse using electro-thermal simulations. We estimate a peak temperature range of 350–450 °C in 40 nm diameter MTJs, underscoring the critical need for thermal management to improve endurance. We suggest several thermal engineering strategies to reduce the peak temperature by up to 120 °C in such devices, which could improve their endurance by at least a factor of 1000× at 0.75 V operating voltage. These results suggest that two-terminal SOT-MRAM could significantly outperform conventional STT-MRAM in terms of endurance, substantially benefiting from thermal engineering. These insights are pivotal for thermal optimization strategies in the development of MRAM technologies. [ABSTRACT FROM AUTHOR]

(a) Background: Technological advancement in the recent years has enabled the application of single photon emission tomography (SPECT) to evaluate myocardial blood flow (MBF). This method offers increased sensitivity in the assessment of coronary health, quantifiable through non-invasive imaging beyond the more conventional methods such as with myocardial perfusion imaging (MPI). (b) Aims: To correlate MBF, derived by dynamic SPECT, both global and by coronary territories to the summed stress scores (SSS) on conventional MPI. (c) Methods: Images obtained from dipyridamole-gated SPECT MPI stress and rest studies performed on recruited subjects were examined. We calculated the global and regional coronary flow reserve (CFR) via a standard software package, taken as the ratio of stress MBF to rest MBF, using CFR 50%). We observed a progressive reduction in global and regional CFR across the normal SSS category to that of severely abnormal (SSS >13). Reduced global CFR with correspondent lower CFR across the regional arteries were detected in scans within normal limits of MPI scans in subjects who were older (69 ± 7 vs. 62 ± 9 years, p = 0.034). Decreasing CFR was significantly associated with increasing age across the regional arteries. (e) Conclusion: In our study we depict the global and regional MBF values obtained via SPECT MPI in correlation to the respective SSS categories. Our data proposes that dynamic SPECT has a part in refining cardiac risk stratification, particularly in the older adult population, who are at greater risk.

Abstract Background Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta‐analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. Methods We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false‐positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen‐2 were analyzed for functional annotations. Results Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50–0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70–3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21–1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71–2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52–3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. Conclusions The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Abstract Background Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. Methods For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. Results Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7–26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01–54.84; P

Abstract Objective The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. Methods An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. Results Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and − 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC − 4.0%) and H2 of 2018 to H2 2020 (HPC − 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC − 2.7%) and H2 of 2014 to H2 of 2020 (HPC − 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC − 6.0%) and H1 of 2014 to H2 of 2020 (HPC − 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC − 2.5%) and H1 of 2012 to H2 of 2015 (HPC − 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC − 4.5%) and H2 of 2014 to H2 of 2020 (HPC − 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC − 4.9%). Conclusions In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals.

Abstract Background and Aims There is a paucity of information on remdesivir (RDV) use in severe pediatric coronavirus disease 2019 (COVID‐19). We aimed to explore the effectiveness of RDV as the cumulative proportion of pediatric COVID‐19 patients deescalated from Day 5 of high dependency or intensive care unit (HD/ICU). Methods All children ≤18 years admitted to Singapore's largest pediatric hospital from January 1, 2020 to March 18, 2022 were reviewed retrospectively. Patients were included if they were positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on reverse transcriptase polymerase chain reaction, required oxygen, and HD/ICU care. The characteristics and outcomes of those who received RDV or not (no‐RDV) were compared. Results We reviewed 15 children with a median age of 2.5 years (interquartile range [IQR]: 0.8–11.0), of which 7 (46.7%) received RDV. There was no difference in cumulative proportion of children deescalated from Day 5 of HD/ICU care in the RDV versus the no‐RDV group (5/7, 70% vs. 7/8, 87.5%, p = 0.57). The RDV versus no‐RDV group had higher disease severity, that is, WHO Ordinal Scale scores (median 6, IQR: 5–7 vs. 5, IQR: 4–5, p = 0.03), higher procalcitonin levels (ug/L) (median 4.31, IQR: 0.8–24.2 vs. 0.12, IQR: 0.09–0.26, p = 0.02), and longer HD/ICU care days (median 5, IQR: 4–9, vs. 1, IQR: 1–4, p = 0.01). There was no significant difference in hospitalization days. There were no adverse events directly attributable to RDV. None died from COVID‐19 infection. Conclusion Our observational analysis was unable to detect any clear benefit of RDV in terms of reducing duration in HD/ICU. RDV was well‐tolerated in children with severe COVID‐19.

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1β and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.

In this work, a robust epoxy adhesive (EP) @ superhydrophobic SiO2 (SH-SiO2)-based superhydrophobic coating was prepared on the aluminum substrate by a simple one-step spraying strategy. The prepared EP@SH-SiO2 coating exhibits hierarchical micro/nanostructures and is capable of maintaining a contact angle of more than 150° after 1000 cm of abrasion length and 80 tape-peeling repetitions. Molecular dynamics (MD) simulations and quantum mechanics calculations show that the improved mechanical resistance is attributed to the enhanced interfacial interaction between the EP@SH-SiO2 coating and the underlying substrate induced by the epoxy adhesive. Electrochemical measurements in 3.5 wt% NaCl solution show the corrosion inhibition efficiency of the EP@SH-SiO2 coating reaches up to 99.99%, and even after 8 days of immersion, the low frequency impedance modulus of the EP@SH-SiO2 sample is still ∼1 order of magnitude higher than that bare aluminum, demonstrating excellent long-term corrosion protection. The diffusion behavior of the corrosive medium in the EP@SH-SiO2 coating was revealed by MD simulation to support the experimental results. Additionally, the EP@SH-SiO2 coating exhibits good chemical stability and hydrophobic repair properties. This work will provide a new perspective for the preparation and study of robust superhydrophobic aluminum for corrosion protection properties.

Vincetoxicum junzifengense B.J. Ye and S.P. Chen 2022 is a newly described species which belongs to the genus Vincetoxicum in the family Apocynaceae. The complete plastid genome of Vincetoxicum junzifengense B.J. Ye and S.P. Chen 2022 was determined and analyzed in this study. The total chloroplast genome was 159,666 bp in length, consisting of a large single-copy region of 90,565 bp, a small single-copy region of 19,691 bp, and two inverted repeat regions of 24,705 bp. The genome contained 131 genes, including 85 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. Phylogenetic analysis indicated that V. junzifengense is sister to V. versicolor.

Objective To detect the main amino acid sites in the ion-conducting pore of the human α7 nicotinic acetycholine receptor(α7nAChR) by two-electrode voltage-clamp. Methods The amino acids in the transmembrane region M2 of α7 nAChR subunit (from Leu248 to Ala258) were mutated to hydrophilic serine by site-directed mutagenesis. cRNA was synthesized in vitro and injected into Xenopus oocytes. After 1～3 days, the function of wild type α7 nAChR and its mutants were detected by two-electrode voltage-clamp. Results After the hydrophilic mutation on the second transmembrane domain, it was indicated that the mutations of the hydrophobic residues (L248,V252,L255 and L256) to hydrophilic ones significantly decrease the EC50 values of the receptor to agonist acetylcholine. The hydrophilic mutations of these four M2 residues resulted in a dramatic leftward shift of the dose-response curve and decrease desensitization. Moreover, the desensitization rate was positively correlated to the EC50 values in log scale. Conclusions The residues L248, V252, L256 and L255 in the transmembrane M2 of α7 nAChR are the main sites to construct the ion-conducting pore.

The Ilex L. (hollies) genus of Aquifoliaceae shows high species diversity in tropical and subtropical regions of Asia and South America. Throughout the range of the genus, Ilex species have been widely used in beverage and medicine production and as ornamentals. Here, we assembled a high-quality, chromosome-level genome of Ilex latifolia, which has extremely high economic value because of its useful secondary metabolite production and the high ornamental value of its decorative red berries. The 99.8% genome sequence was anchored to 20 pseudochromosomes, with a total length of 766.02 Mb and a scaffold N50 of 33.45 Mb. Based on the comparative genomic analysis of 14 angiosperm species, we recovered I. latifolia as the sister group to all other campanulids. Two whole-genome duplication (WGD) events were identified in hollies: one shared ancient WGD in the ancestor of all eudicots and a recent and independent WGD in hollies. We performed a genome-wide search to screen candidate genes involved in the biosynthesis of pentacyclic triterpenoid saponins in I. latifolia. Three subfamilies of CYP450 (CYP71A, CYP72A, and CYP716A) appear to have expanded. The transcriptomic analysis of I. latifolia leaves at five developmental stages revealed that two CYP716A genes and one CYP72A gene probably play important roles in this biosynthetic pathway. In addition, we totally identified 12 genes in the biosynthesis pathways of pelargonidin and cyanidin and observed their differential expression in green and red fruit pericarps, suggesting an association between pelargonidin and cyanidin biosynthesis and fruit pericarp color change. The accumulation of pelargonidin and cyanidin is expected to play an important role in the ornamental value of I. latifolia. Altogether, this study elucidated the molecular basis of the medicinal and ornamental value of I. latifolia, providing a data basis and promising clues for further applications.