snRNA-seq of human ovaries reveals heat shock proteins are associated with obesity related cancer risk.

Background: Obesity significantly impacts female reproductive health and increases the risk of gynecological tumors. However, the specific transcriptional changes that occur in the ovarian microenvironment during obesity-induced stress and the relationship between obesity and ovarian cancer remain unclear.

Methods: Our study investigated the single-cell landscape of the ovarian cortex in individuals with varying BMI levels by snRNA-seq, revealing weight-stage related cellular composition deviations and expression profile irregularities.

CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.

CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst.

The impact of type 2 diabetes on polycystic ovary syndrome in patients undergoing sleeve gastrectomy.

Study Question: Does the concurrent type 2 diabetes mellitus (T2DM) aggravate the features and prognosis of PCOS in patients undergoing sleeve gastrectomy (SG)?

Summary Answer: For patients undergoing SG with obesity, concurrent T2DM is associated with aggravated metabolic but milder reproductive features of PCOS and did not attenuate the resumption of regular menstruation for up to 1 year after surgery.

What Is Known Already: Women with T2DM have an increased risk of PCOS. However, whether concurrent T2DM further increases the disease burden and treatment difficulty of PCOS in patients with obesity requires further investigation.

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport.

Total weight loss rather than preoperative body mass index correlates with remission of irregular menstruation after sleeve gastrectomy in patients with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. Some retrospective studies with small sample sizes have reported that bariatric metabolic surgery is effective in remission of irregular menstruation in patients with PCOS and obesity. However, the correlation between preoperative body mass index (BMI), postoperative weight loss, and remission of irregular menstruation in patients with obesity and PCOS after sleeve gastrectomy (SG) is lack of consensus.

Deconvolution at the single-cell level reveals ovarian cell-type-specific transcriptomic changes in PCOS.

Background: Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood.

TOX3 deficiency mitigates hyperglycemia by suppressing hepatic gluconeogenesis through FoxO1.

Background: Excessive hepatic glucose production is a hallmark that contributes to hyperglycemia in type 2 diabetes (T2D). The regulatory network governing this process remains incompletely understood. Here, we demonstrate that TOX3, a high-mobility group family member, acts as a major transcriptional driver for hepatic glucose production.

Associations between vaginal microbiota and endometrial polypoid lesions in women of reproductive age: a cross-sectional study.

Research Question: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls?

Design: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort.

Thrombolysis with Recombinant Human Prourokinase 4.5-6 h After Acute Ischemic Stroke: A Phase IIa, Randomized, and Open-Label Multicenter Clinical Trial.

Background: Ischemic stroke is a major cause of disability and death worldwide. A narrow therapeutic window profoundly constrained the utilization of alteplase.

Objectives: To investigate therapeutic effects and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke (AIS) in the 4.

Epigallocatechin-3-gallate improves the quality of maternally aged oocytes.

The decline in female fertility as age advances is intricately linked to the diminished developmental potential of oocytes. Despite this challenge, the strategies available to enhance the quality of aged oocytes remain limited. Epigallocatechin-3-gallate (EGCG), characterised by its anti-inflammatory, antioxidant and tissue protective properties, holds promise as a candidate for improving the quality of maternally aged oocytes.

Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity.

Obesity, which can arise from genetic or environmental factors, has been shown to cause serious damages to the reproductive system. The ovary, as one of the primary regulators of female fertility, is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment (OME). Despite its importance, the effect of obesity on the entire ovary remains poorly documented.

Admission NLPR predicts long-term mortality in patients with acute ischemic stroke: A retrospective analysis of the MIMIC-III database.

Background: The neutrophil to lymphocyte*platelet ratio (NLPR) is a new index based on platelets, neutrophils, and lymphocytes associated with the prognosis of patients with infectious diseases and cancer. However, its use in acute ischemic stroke has rarely been reported. This study examined the relationship between levels of systemic immunoinflammatory indices at admission and patient outcomes at different times after onset to assess stroke prognosis by NLPR.

Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial.

Importance: Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS).

Objective: To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

Research Question: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?

Design: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing.

Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study.

A balanced vaginal microbiome dominated by can help promote women's reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thoroughly explored. In this nested case-control study based on an assisted reproductive technology follow-up cohort, we prospectively assessed the association between pregestational vaginal microbiomes with HDP by collecting vaginal swabs from 75 HDP cases (HDP group) and 150 controls (NP group) and using 16S amplicon sequencing for bacterial identification.

THADA inhibition in mice protects against type 2 diabetes mellitus by improving pancreatic β-cell function and preserving β-cell mass.

Impaired insulin secretion is a hallmark in type 2 diabetes mellitus (T2DM). THADA has been identified as a candidate gene for T2DM, but its role in glucose homeostasis remains elusive. Here we report that THADA is strongly activated in human and mouse islets of T2DM.

Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure.

Total fertilization failure (TFF), which refers to fertilization failure in all mature oocytes, accounting for 5%-10% of in vitro fertilization (IVF) cycles and 1%-3% of intracytoplasmic sperm injection (ICSI) cycles in human. In this study, we recruited three unrelated primary infertile men with repeated cycles of TFF and performed whole-exome sequencing to identify the potential pathogenic variants. We identified homozygous or compound-heterozygous variants of paternal-effect genes ACTL7A and PLCZ1 that followed a Mendelian recessive inheritance pattern.

Variations in mitochondrial DNA coding and D-loop region are associated with early embryonic development defects in infertile women.

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects.