Selenadiazole-Induced Hela Cell Apoptosis through the Redox Oxygen Species-Mediated JAK2/STAT3 Signaling Pathway.

Cervical cancer is a significant global health concern, and novel therapeutic strategies are continually being sought to combat this disease. In recent years, selenadiazole found latent therapeutic effects on tumors. Herein, investigating the mechanism of selenadiazole in Hela cells holds promise for advancing cervical cancer treatment. Hela cells, a widely utilized model for studying cervical cancer, were treated with selenadiazole, and cell viability was assessed by using the cell counting kit-8 (CCK-8) assay. Changes in mitochondrial membrane potential were evaluated using JC-1 staining, while apoptosis induction was examined using AnnexinV-PI double staining. Intracellular ROS levels were measured by using specific fluorescent probes and the ELIASA system. Additionally, Western blotting was performed to assess the activation of related proteins in response to selenadiazole. Data analysis was performed using GraphPad. Exposure to selenadiazole led to a substantial increase in intracellular redox oxygen species (ROS) levels in Hela cells. Importantly, the induction of ROS by selenadiazole was associated with a marked increase in mitochondrial apoptosis, as evidenced by elevated levels of AnnexinV-positive cells, the JC-1 monomer, caspase-9, and Bcl-2. Furthermore, activation of the JAK2/STAT3 pathway was observed following the selenadiazole treatment. Selenadiazole holds the potential to suppress tumor growth in cervical cancer cells by increasing reactive oxygen species (ROS) levels and inducing mitochondrial apoptosis via the JAK2/STAT3 pathway. This study offers valuable insights into potential cervical cancer therapies and underscores the need for further research into the specific mechanisms of selenadiazole.

PRDM14 extinction enables the initiation of trophoblast stem cell formation.

Trophoblast stem cells (TSCs) can be chemically converted from embryonic stem cells (ESCs) in vitro. Although several transcription factors (TFs) have been recognized as essential for TSC formation, it remains unclear how differentiation cues link elimination of stemness with the establishment of TSC identity. Here, we show that PRDM14, a critical pluripotent circuitry component, is reduced during the formation of TSCs. The reduction is further shown to be due to the activation of Wnt/ß-catenin signaling. The extinction of PRDM14 results in the erasure of H3K27me3 marks and chromatin opening in the gene loci of TSC TFs, including GATA3 and TFAP2C, which enables their expression and thus the initiation of the TSC formation process. Accordingly, PRDM14 reduction is proposed here as a critical event that couples elimination of stemness with the initiation of TSC formation. The present study provides novel insights into how induction signals initiate TSC formation.

Modulations of resting-static functional connectivity on insular by electroacupuncture in subjective tinnitus.

Objective: To explore the modulations of electroacupuncture in subjective tinnitus (ST) by comparing the difference of functional connectivity (FC) in ST patients and healthy volunteers between the insular (INS) and the whole brain region. Methods: A total of 34 ST patients were selected into electroacupuncture group (EG) and 34 age- and sex-matched normal subjects were recruited into control group (CG). The EG received acupuncture at SI19 (Tinggong), GB11 (Touqiaoyin), TE17 (Yifeng), GV20 (Baihui), GV15 (Yamen), GV14 (Dazhui), SJ13 (Zhongzhu), among which the points of SI19 and GB11 were connected to the electroacupuncture instrument with the density wave of 2/50 Hz, and 3 treatments per week for 10 sessions in total. The severity of tinnitus was evaluated by Tinnitus Handicap Inventory (THI), the hearing status was recorded using pure tone audiometry, and resting-state functional magnetic resonance imaging (rs-fMRI) was performed on the brain before and after treatment, the CG received no intervention yet only rs-fMRI data were collected. Results: With the electroacupuncture treatment, the total THI score, average air conduction threshold of patients of EG were significantly lower than before (p < 0.01), and the total effective rate was 88.24%. Compared with CG, FC of ST patients between INS and left superior temporal gyrus and right hippocampal significantly decreased before treatment, while FC of ST patients between INS and right superior frontal gyrus, left middle frontal gyrus and right anterior cuneus significantly decreased after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of ST patients between the INS and right middle frontal gyrus, left superior frontal gyrus and right paracentral lobule showed a significant decrease after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). In addition, THI score in EG was negatively correlated with the reduction of FC value in INS-left superior frontal gyrus before treatment (r = -0.41, p = 0.017). Therefore, this study suggests that abnormal FC of INS may be one of the significant central mechanisms of ST patients and can be modulated by electroacupuncture. Discussion: Electroacupuncture treatment can effectively reduce or eliminate tinnitus symptoms in ST patients and improve the hearing by decreasing FC between the INS and the frontal and temporal brain regions.

Loss of FoxO1 activates an alternate mechanism of mitochondrial quality control for healthy adipose browning.

Browning of white adipose tissue is hallmarked by increased mitochondrial density and metabolic improvements. However, it remains largely unknown how mitochondrial turnover and quality control are regulated during adipose browning. In the present study, we found that mice lacking adipocyte FoxO1, a transcription factor that regulates autophagy, adopted an alternate mechanism of mitophagy to maintain mitochondrial turnover and quality control during adipose browning. Post-developmental deletion of adipocyte FoxO1 (adO1KO) suppressed Bnip3 but activated Fundc1/Drp1/OPA1 cascade, concurrent with up-regulation of Atg7 and CTSL. In addition, mitochondrial biogenesis was stimulated via the Pgc1α/Tfam pathway in adO1KO mice. These changes were associated with enhanced mitochondrial homeostasis and metabolic health (e.g., improved glucose tolerance and insulin sensitivity). By contrast, silencing Fundc1 or Pgc1α reversed the changes induced by silencing FoxO1, which impaired mitochondrial quality control and function. Ablation of Atg7 suppressed mitochondrial turnover and function, causing metabolic disorder (e.g., impaired glucose tolerance and insulin sensitivity), regardless of elevated markers of adipose browning. Consistently, suppression of autophagy via CTSL by high-fat diet was associated with a reversal of adO1KO-induced benefits. Our data reveal a unique role of FoxO1 in coordinating mitophagy receptors (Bnip3 and Fundc1) for a fine-tuned mitochondrial turnover and quality control, underscoring autophagic clearance of mitochondria as a prerequisite for healthy browning of adipose tissue.

Characteristics of cervicovaginal microflora at different cervical maturity during late pregnancy: A nested case-control study.

OBJECTIVE: The mechanism of cervical ripening in late pregnancy is still unclear. The vaginal microbiome has been reported to correlate with the preterm birth and short cervix in pregnant women. However, the associations between the cervical maturity and the vaginal microbiome are still poorly understood. We aim to analyze the cervicovaginal microflora in women with ripe cervix and in those who are unripe when delivering at term. METHODS: Cervicovaginal swabs were collected between 40 and 41 weeks of gestation from the following 2 different groups of patients: ripe group (n = 25) and unripe group (n = 25). Samples were tested using 16S ribosomal RNA gene high-throughput sequencing and analyzed by bioinformatics platform. RESULTS: This study highlights the relationship between cervical maturity during late pregnancy and the composition of the cervicovaginal microflora. Both α- and ß-diversity analyses demonstrated significant differences between women with a ripe cervix and those with an unripe cervix. Notably, the Lactobacillus profile was found to be closely linked to cervical maturity. There was a significant difference in the vaginal community state type, with CST IV being more prevalent in women with an unripe cervix. Furthermore, the association between CST IV and the unripe cervix group, as indicated by the odds ratio of 8.6, underscores its relevance in evaluating cervical maturity, when compared to other Lactobacillus-dominant community state types. Additionally, several bacterial taxa, particularly Lactobacillus, exhibited differential relative abundances between the two groups. CONCLUSION: This study provided significant evidence regarding the relationship between the vaginal microbiome and cervical maturity, highlighting the differential diversity, community state types, and specific bacterial taxa, such as Lactobacillus, that are associated with cervical maturation status. These findings contributed to our understanding of the dynamics of the cervicovaginal microflora during late pregnancy and its implications for cervical health.

A Galectin-9-Driven CD11chigh Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia.

BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.

Preeclampsia/eclampsia impacts the structure and function of neonatal hearts probably by reducing myocardial compaction.

PURPOSE: Preeclampsia/Eclampsia (PE/E) poses significant risks to neonatal cardiac health. Traditional echocardiographic methods have limitations in detailing these impacts. This study hypothesized that echocardiographic radiomics could provide a more comprehensive assessment of the cardiac changes in neonates affected by PE/E. METHOD: In a comprehensive analysis, 2594 neonates underwent echocardiographic screening. From these, 556 were selected for detailed radiomics analysis, focusing on cardiac shape, movement, and texture features. A multiblock sparse partial least squares (sPLS) model integrated these features to assess their association with PE/E. RESULTS: Newborns from PE/E-affected pregnancies displayed lower left ventricular ejection fractions compared to the control group (61.1 % vs. 66.2 %). Our radiomics approach extracted 15,494 features per neonate, with the sPLS model identifying 17 features significantly correlated with PE/E. Among these, texture features representing myocardial non-compaction were most strongly correlated with PE/E (correlation coefficient r = 0.63). Detailed visualization of these texture features suggested that PE/E might lead to more pronounced myocardial non-compaction, characterized by a thicker non-compaction layer and increased cardiac trabeculation. CONCLUSIONS: Our findings demonstrate the potential of echocardiographic radiomics as a tool for assessing the impact of PE/E on neonatal cardiac function. The correlation between PE/E and myocardial non-compaction underlines the need for enhanced cardiac monitoring in neonates born to PE/E-affected mothers. This study contributes to a better understanding of PE/E's cardiac implications, potentially guiding future clinical practices.

Comprehensive reference intervals for white blood cell counts during pregnancy.

BACKGROUND: White blood cell (WBC) count increases during pregnancy, necessitating reliable reference intervals for assessing infections and pregnancy-related complications. This study aimed to establish comprehensive reference intervals for WBC counts during pregnancy. METHODS: The analysis included 17,737 pregnant women, with weekly WBC count measurements from pre-pregnancy to postpartum. A threshold linear regression model determined reference intervals, while Harris and Boyd's test partitioned the intervals. RESULTS: WBC count exhibited a significant increase during pregnancy, characterized by a rapid rise before 7 weeks of gestation, followed by a plateau. Neutrophils primarily drove this increase, showing a similar pattern. The threshold regression model and Harris and Boyd's test supported partitioned reference intervals for WBC counts: 4.0-10.0 × 10^9/L for < = 2 weeks, 4.7-11.9 × 10^9/L for 3-5 weeks, and 5.7-14.4 × 10^9/L for > = 6 weeks of gestation. These reference intervals identified pregnant women with high WBC counts, who had a higher incidence of pregnancy-related complications including placenta previa, oligohydramnios, secondary uterine inertia, and intrauterine growth restriction. CONCLUSION: This study establishes comprehensive reference intervals for WBC counts during pregnancy. Monitoring WBC counts is clinically relevant, as elevated levels are associated with an increased risk of infection and pregnancy-related complications.

Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy.

BACKGROUND: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. OBJECTIVE: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. STUDY DESIGN: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). RESULTS: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). CONCLUSION: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

Association of serum 25-hydroxyvitamin D levels with all-cause and cause-specific mortality among postmenopausal females: results from NHANES.

BACKGROUND: Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States. METHODS: 6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001-2018) were included in this study. The mortality status of the follow-up was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. We used cox proportional hazards models to estimate the association of serum 25(OH)D concentrations and mortality of postmenopausal females. RESULTS: The mean level of serum 25(OH)D was 72.57 ± 29.93 nmol/L, and 65.34% had insufficient vitamin D. In postmenopausal females, low serum 25(OH)D concentrations were significantly associated with higher levels of glycohemoglobin, glucose, and lower levels of HDL. During follow-up, 1448 all-cause deaths occurred, including 393 cardiovascular disease (CVD)-related deaths and 263 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly related with lower all-cause and CVD mortality. In addition, serum 25(OH)D presented a L-shaped relationship with all-cause mortality, while appeared a U-shaped with CVD mortality, and the cut-off value is 73.89 nmol/L and 46.75 nmol/L respectively. CONCLUSIONS: Low serum 25(OH)D levels are associated with the higher risk of all-cause and CVD mortality in postmenopausal females. These findings provide new ideas and targets for the health management of postmenopausal women.

Trimester-specific reference intervals for hemoglobin A1c in non-diabetic pregnancy in a Chinese population.

BACKGROUND: Physiological glycated hemoglobin (HbA1c) values in each trimester are not well defined. This study aimed to determine trimester-specific reference intervals for HbA1c levels in non-diabetic pregnant women in China. METHODS: In this cross-sectional study, 5,042 Chinese pregnant women from 6 to 41 weeks of gestation were screened. An inclusion of 4,134 non-diabetic women was made to determine the reference intervals, they were divided into three trimesters: trimester 1 (T1), 6 weeks to 13 weeks + 6 days, trimester 2 (T2), 14 weeks to 27 weeks + 6 days, and trimester 3 (T3), 28 weeks to 41 weeks + 6 days. A total of 4,134 women (T1 n = 760, T2 n = 1,953, and T3 n = 1,421) provided blood samples which were analyzed for HbA1c concentrations. HbA1c was measured using high-performance liquid chromatography. The median and percentile (2.5th to 97.5th) for the HbA1c reference intervals were calculated for each trimester. RESULTS: In total, 8,732 HbA1c measurements were taken. Reference intervals for HbA1c expressed as median and percentile (2.5th to 97.5th) for each trimester were: T1: 4.7 (4.0-5.5%), T2: 4.5 (3.9-5.3%), and T3: 4.8 (4.1-5.7%) respectively. The HbA1c levels were significantly lower in the second trimester compared to those in the first trimester (p < 0.0001), and higher in the third trimester compared to the second trimester (p < 0.0001). CONCLUSIONS: The reference intervals for HbA1c levels were 3.9-5.7% with upper limits of 5.5% in the first trimester, 5.3% in the second trimester, and 5.7% in the third trimester. These findings highlight the importance of considering trimester-specific reference intervals for HbA1c in non-diabetic pregnant women to promote maternal and fetal health.

The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression.

The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes HDAC5/p16INK4a was studied in GC cells, and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP). Additionally, the role of the miR-4256/HDAC5/p16INK4a axis in GC was studied using in vitro and in vivo experiments. Finally, the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments. miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues; in vitro and in vivo results showed that miR-4256 promoted GC growth and progression. Mechanistically, miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells, and then restrained the expression of p16INK4a through the epigenetic modulation of HDAC5 at the p16INK4a promoter. Furthermore, miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells. Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16INK4a axis, which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.

Cyclocarya paliurus leaves extracts alleviate metabolic phenotypes in Chinese T2DM patients by modulating gut microbiota and metabolites: a clinical randomized controlled trial.

Objective: We aimed to investigate the effect of Cyclocarya paliurus leaves extracts (CP) on glucose and blood lipid metabolism and its relationship with intestinal flora in type 2 diabetes mellitus (T2DM) patients. Methods: In this open-label, 84-day randomized controlled trial, a total of 38 T2DM patients were randomly assigned to the CP group or the Glipizide group (G group) in a 2:1 ratio. T2DM-associated metabolic phenotypes, gut microbiota and metabolites including short-chain fatty acids (SCFAs) and bile acids (BAs) were detected. Results: At the end of intervention, CP, like Glipizide, significantly improved HbA1c level and other glucose metabolism parameters (fasting plasma glucose (FBG), 2-hour post-meal blood glucose (2hPBG), the area under curve of oral glucose tolerance test glucose (OGTT glucose AUC)). Moreover, CP also resulted in the significant improvement in the levels of blood lipid and blood pressure. Notably, the improvement in blood lipid(triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c)) and blood pressure (diastolic blood pressure (DBP)) was significantly greater in the CP group compared with the G group. Furthermore, the liver and kidney function parameters did not significantly change in both CP group and the G group over the 84-day period. Additionally, the enrichment of potentially beneficial bacteria (Faecalibacterium and Akkermansia), SCFAs and unconjugated BAs and the depletion of potential pathogenic bacteria (Prevotella_9) and conjugated BAs were observed in the CP group, while the abundances of the gut microbial were kept stable in the G group after intervention. Conclusion: CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than glipizide by regulating gut microbiota and metabolites in T2DM patients, with no significant effects on liver and kidney function.

Effects of Right Lateral Position on Changes of Fetal Hemodynamics in Late Pregnancy.

OBJECTIVE: We aim to evaluate the effect of right lateral position on fetal hemodynamics (including umbilical artery [UA] and middle cerebral artery (MCA) blood flow-velocity waveform). METHODS: In total, 150 low-risk singleton full-term pregnant women were included in the study from November 2021 to January 2022. Doppler flow velocity waveforms of the fetal UA and MCA tested by ultrasound were collected in gestation of 37-40 weeks. Computational analysis was performed using the one-way ANOVA test. RESULTS: Compared with the maternal left lateral position, there was a significant increase in Doppler indices of UA-RI (P = .033), UA-S/D (P = .019) and MCA-PSV (P = .021) and a significant decrease in MCA-RI (P = .030) in the supine position group. There was no statistical significance in all Doppler indices between the left and right lateral position (P > .05). Among the Doppler indices of three different maternal positions, there was no significance in both UA-PI and MCA-PI (P > .05). CONCLUSION: There were no significant differences on changes of the fetal hemodynamics between left and right lateral positions. Pregnant women could adopt to lie in the left or right lateral position alternately to relieve the discomfort in late pregnancy.

The Effects of Labor Epidural Analgesia on Maternal and Fetal Hemodynamics: A Prospective Observation Study.

PURPOSE: This study aimed to investigate the effect of epidural analgesia (EA) on maternal and fetal hemodynamics. METHODS: A prospective single-center observational study was conducted from March 2022 to May 2022 on low-risk singleton pregnancies who received prenatal care at 37-40 weeks and delivered at our hospital. Pre- and post-EA, maternal and fetal hemodynamics, including maternal parameters of mean arterial pressure (MAP), heart rate (HR) and saturation of pulse oxygen (SPO2 ), fetal heart rate (FHR), Doppler flow parameters of umbilical artery (UA), middle cerebral artery (MCA), and uterine artery (UtA) during labor were measured before epidural insertion (T0), and 15 (T1), 30 (T2), and 60 (T3) minutes after. Computational analysis was performed using a one-way ANOVA test. RESULTS: In total, 100 singleton pregnant women were enrolled. After EA, maternal MAP, HR, and SPO2 were significantly lower than baseline values at all times except for HR in T3 and remained lower for the study's duration (P < .05). As for FHR, there was no significant difference between pre- and post-epidural. The mean UtA-PI (pulsatility index), UA-PI, UA-RI (resistance index), and UA-S/D (systolic/diastolic ratio) were not significantly modified after EA. Nevertheless, MCA-PI and RI significantly decreased in 15 minutes after initiating EA compared with T0 values (P < .05), and MCA-PSV (resistance index and peak systolic velocities) was significantly increased compared with T0 at all times (P < .05). The above changes were all within the normal range. CONCLUSION: Although maternal MAP, HR, and SPO2 significantly decreased after EA, fetal hemodynamics remained relatively stable.

FoxO1 regulates adipose transdifferentiation and iron influx by mediating Tgfß1 signaling pathway.

Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of transdifferentiation remains incompletely understood. Here we show that the transcription factor FoxO1 regulates adipose transdifferentiation by mediating Tgfß1 signaling pathway. Tgfß1 treatment induced whitening phenotype in beige adipocytes, reducing UCP1 and mitochondrial capacity and enlarging lipid droplets. Deletion of adipose FoxO1 (adO1KO) dampened Tgfß1 signaling by downregulating Tgfbr2 and Smad3 and induced browning of adipose tissue in mice, increasing UCP1 and mitochondrial content and activating metabolic pathways. Silencing FoxO1 also abolished the whitening effect of Tgfß1 on beige adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, and smaller adipocytes than the control mice. The browning phenotype in adO1KO mice was associated with an increased iron content in adipose tissue, concurrent with upregulation of proteins that facilitate iron uptake (DMT1 and TfR1) and iron import into mitochondria (Mfrn1). Analysis of hepatic and serum iron along with hepatic iron-regulatory proteins (ferritin and ferroportin) in the adO1KO mice revealed an adipose tissue-liver crosstalk that meets the increased iron requirement for adipose browning. The FoxO1-Tgfß1 signaling cascade also underlay adipose browning induced by ß3-AR agonist CL316243. Our study provides the first evidence of a FoxO1-Tgfß1 axis in the regulation of adipose browning-whitening transdifferentiation and iron influx, which sheds light on the compromised adipose plasticity in conditions of dysregulated FoxO1 and Tgfß1 signaling.

Magnetic-field modulation of topological electronic state and emergent magneto-transport in a magnetic Weyl semimetal.

The modulation of topological electronic state by an external magnetic field is highly desired for condensed-matter physics. Schemes to achieve this have been proposed theoretically, but few can be realized experimentally. Here, combining transverse transport, theoretical calculations, and scanning tunneling microscopy/spectroscopy (STM/S) investigations, we provide an observation that the topological electronic state, accompanied by an emergent magneto-transport phenomenon, was modulated by applying magnetic field through induced non-collinear magnetism in the magnetic Weyl semimetal EuB6. A giant unconventional anomalous Hall effect (UAHE) is found during the magnetization re-orientation from easy axes to hard ones in magnetic field, with a UAHE peak around the low field of 5 kOe. Under the reasonable spin-canting effect, the folding of the topological anti-crossing bands occurs, generating a strong Berry curvature that accounts for the observed UAHE. Field-dependent STM/S reveals a highly synchronous evolution of electronic density of states, with a dI/dV peak around the same field of 5 kOe, which provides evidence to the folded bands and excited UAHE by external magnetic fields. This finding elucidates the connection between the real-space non-collinear magnetism and the k-space topological electronic state and establishes a novel manner to engineer the magneto-transport behaviors of correlated electrons for future topological spintronics.

Scaling of Berry-curvature monopole dominated large linear positive magnetoresistance.

The linear positive magnetoresistance (LPMR) is a widely observed phenomenon in topological materials, which is promising for potential applications on topological spintronics. However, its mechanism remains ambiguous yet, and the effect is thus uncontrollable. Here, we report a quantitative scaling model that correlates the LPMR with the Berry curvature, based on a ferromagnetic Weyl semimetal CoS2 that bears the largest LPMR of over 500% at 2 K and 9 T, among known magnetic topological semimetals. In this system, masses of Weyl nodes existing near the Fermi level, revealed by theoretical calculations, serve as Berry-curvature monopoles and low-effective-mass carriers. Based on the Weyl picture, we propose a relation [Formula: see text], with B being the applied magnetic field and [Formula: see text] the average Berry curvature near the Fermi surface, and further introduce temperature factor to both MR/B slope (MR per unit field) and anomalous Hall conductivity, which establishes the connection between the model and experimental measurements. A clear picture of the linearly slowing down of carriers, i.e., the LPMR effect, is demonstrated under the cooperation of the k-space Berry curvature and real-space magnetic field. Our study not only provides experimental evidence of Berry curvature-induced LPMR but also promotes the common understanding and functional designing of the large Berry-curvature MR in topological Dirac/Weyl systems for magnetic sensing or information storage.

Linear and non-linear Mendelian randomization analyses of sex-specific associations between sleep duration and hyperuricemia.

Background: Observational studies have suggested a potential non-linear association between sleep duration and hyperuricemia. However, the causal nature and sex-specific differences are poorly understood. We aimed to determine the shape of sex-specific causal associations between sleep duration and hyperuricemia in the UK Biobank. Methods: Logistic regression was used to investigate the observational association between self-reported sleep duration and hyperuricemia among 387,980 white British participants (mean age: 56.9 years and 46.0% males). Linear and non-linear Mendelian Randomization (MR) analyses were performed to assess the causal association between continuous sleep duration and hyperuricemia. The causal effects of genetically predicted short (<7 h) and long (>8 h) sleep durations on hyperuricemia were further estimated, respectively. Results: Traditional observational analysis suggested U- and J-shaped associations between sleep duration and hyperuricemia in females and males, respectively. Linear MR did not support the causal effect of sleep duration on hyperuricemia. Non-linear MR demonstrated an approximately U-shaped causal association between continuous sleep duration and hyperuricemia in overall participants and females, but not in males. Genetically predicted short sleep duration was significantly associated with hyperuricemia in females (OR [95% CI]: 1.21 [1.08-1.36]; P = 0.001), but not in males (1.08 [0.98-1.18]; P = 0.137). By contrast, genetically predicted long sleep duration was not significantly associated with the risk of hyperuricemia in either females or males. Conclusion: Genetically predicted short sleep duration is a potential causal risk factor for hyperuricemia for females but has little effect on males. Long sleep duration does not appear to be causally associated with hyperuricemia.