Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients.

Background: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence.

Theophylline derivatives promote primordial follicle activation via cAMP-PI3K/Akt pathway and ameliorate fertility deficits in naturally aged mice.

In elderly women and patients with premature ovarian insufficiency (POI), activating their remaining dormant primordial follicles is challenging. In this study, we found that phosphodiesterase (PDE) subtypes were expressed mainly in primordial follicle oocytes. The specific PDE inhibitors and theophylline derivatives (aminophylline, dyphylline, and enprofylline) activated primordial follicles in neonatal mice by ovary culture and intraperitoneal injection.

Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity.

Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage.

Voices: Challenges and opportunities in regulating the immune system.

The rise of immunotherapy and mRNA vaccines has underscored the power of modulating the immune system for a desired response. In this Voices piece, the Cell Chemical Biology editors ask researchers from a range of backgrounds: what are some major challenges and opportunities facing the field in coming years?

[Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments].

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.

Humoral and cellular immune responses in persons with rheumatoid arthritis after a third dose of mRNA COVID-19 vaccine.

Objective: Disease-modifying anti-rheumatic drugs (DMARDs) that treat rheumatoid arthritis (RA) may reduce immune responses to COVID-19 vaccination. We compared humoral and cell-mediated immunity before and after a 3rd dose of mRNA COVID vaccine in RA subjects.

Methods: RA patients that received 2 doses of mRNA vaccine enrolled in an observational study in 2021 before receiving a 3rd dose.

Mifepristone increases AQP1 mRNA expression, angiogenesis, and cell permeability through the ERK MAPK pathway.

Aims: The purpose of this study was to investigate the mechanism of mifepristone serves as an anti-implantation contraceptive drug on aquaporins 1 (AQP1) expression.

Methods: Human umbilical vein endothelial cells (HUVECs) were used to detect the effects of different concentrations of mifepristone (0, 0.065, 0.

SARS-CoV-2 epitope-specific CD4 memory T cell responses across COVID-19 disease severity and antibody durability.

CD4 T cells are central to long-term immunity against viruses through the functions of T helper 1 (T1) and T follicular helper (T) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4 T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls.

Immune recall improves antibody durability and breadth to SARS-CoV-2 variants.

Key features of immune memory are greater and faster antigen-specific antibody responses to repeat infection. In the setting of immune-evading viral evolution, it is important to understand how far antibody memory recognition stretches across viral variants when memory cells are recalled to action by repeat invasions. It is also important to understand how immune recall influences longevity of secreted antibody responses.

Antibodies induced by an ancestral SARS-CoV-2 strain that cross-neutralize variants from Alpha to Omicron BA.1.

Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many human antibodies, especially those in widely distributed ("public") classes. Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection.

Prevalence of genotype-specific human papillomavirus in cytology specimens and cervical biopsies, and its implication in cervical cancer risk stratification: a retrospective study of 10647 cases.

This study aimed to describe the risk stratification of squamous cell carcinoma (SCC) and its precursor lesions based on HPV E6/E7 mRNA genotyping. 10647 hrHPV+ women (mean age 40.8 years), who had concurrent cytology and follow-up biopsy results available between September 2016 and May 2020, met the inclusion criteria and were selected for immediate risk analysis.

HMGB1 regulates lipopolysaccharide-induced cellular dysfunction in HTR8/SVneo cells: Implications for the role of HMGB1 in unexplained spontaneous miscarriage.

Introduction: Approximately half of miscarriages are of an unknown aetiology and are likely characterized by aberrant inflammation at the uteroplacental interface. High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that participates in the pathological inflammatory response. The present study investigated the role of HMGB1 in inflammation-induced damage in trophoblasts and elucidated the underlying mechanism.

Primary ovarian serous carcinomas with extensive squamous differentiation: a case report and literature review.

Background: Primary ovarian serous carcinomas (OSC) with extensive squamous differentiation is a rare, and histological diagnostic criteria and biological behavior have not been fully established. We present an extremely rare case of primary OSC of the ovary with squamous differentiation.

Case Presentation: A 58-year-old (gravidity 3, parity 2) female was admitted complaining of abdominal distention for 6 months.

Ursodeoxycholic acid improves pregnancy outcome in patients with intrahepatic cholestasis during pregnancy: A protocol for systematic review and meta-analysis.

Background: Intrahepatic cholestasis of pregnancy (ICP) is a common complication in the third trimester of pregnancy, which may result in premature delivery, fetal distress, stillbirth, and other adverse pregnancy outcomes. Ursodeoxycholic acid (UDCA) is a first-line treatment for ICP and has been controversial in improving adverse pregnancy outcomes. The purpose of this protocol is to systematically evaluate the effect of UDCA on pregnancy outcomes in patients with intrahepatic cholestasis during pregnancy.

A new emu genome illuminates the evolution of genome configuration and nuclear architecture of avian chromosomes.

Emu and other ratites are more informative than any other birds in reconstructing the evolution of the ancestral avian or vertebrate karyotype because of their much slower rate of genome evolution. Here, we generated a new chromosome-level genome assembly of a female emu, and estimated the tempo of chromosome evolution across major avian phylogenetic branches, by comparing it to chromosome-level genome assemblies of 11 other bird and one turtle species. We found ratites exhibited the lowest numbers of intra- and inter-chromosomal changes among birds since their divergence with turtles.

Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production.

Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19.

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre-COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID-19 patient antibodies primarily recognized spike protein and nucleoprotein.

DNA vaccine protection against SARS-CoV-2 in rhesus macaques.

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2.

Seminal plasma cell-free mitochondrial DNA copy number is associated with human semen quality.

Objective: Previous studies have shown that mitochondrial DNA (mtDNA) copy number in human sperm is associated with semen quality. This study examines whether there is association between seminal cell-free mtDNA copy number and human semen parameters.

Study Design: Seminal cell-free mtDNA copy number was measured in 205 men.

Microbial symbionts regulate the primary Ig repertoire.

The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape preimmune Ig repertoires, expressed on IgM IgD B cells as B cell receptors (BCRs), are poorly defined. Here, we studied germ-free mice and conventionalized littermates to explore the hypothesis that symbiotic microbes help shape the preimmune Ig repertoire.

Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women.

Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4 T cells compared to those with Lactobacillus crispatus-dominant communities.

Quantitative Proteomics Analysis of VEGF-Responsive Endothelial Protein S-Nitrosylation Using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and LC-MS/MS.

Adduction of a nitric oxide moiety (NO•) to cysteine(s), termed S-nitrosylation (SNO), is a novel mechanism for NO to regulate protein function directly. However, the endothelial SNO-protein network that is affected by endogenous and exogenous NO is obscure. This study was designed to develop a quantitative proteomics approach using stable isotope labeling by amino acids in cell culture for comparing vascular endothelial growth factor (VEGFA)- and NO donor-responsive endothelial nitroso-proteomes.