Integrated multi-omics analysis reveals complement component 3 as a central driver of immune dysregulation in polycystic ovary syndrome

BackgroundPolycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with a complex pathophysiology, affecting various aspects of women’s health. Despite its widespread impact, the molecular basis and immunological aspects of PCOS remain insufficiently understood, limiting effective diagnosis and treatment strategies.ObjectiveThis study aims to elucidate the molecular and immunological landscape of PCOS by integrating gene expression profiles from healthy and PCOS-affected ovaries using both bulk and single-cell omics data, with the goal of constructing a comprehensive bioinformatics network that identifies potential biomarkers and therapeutic targets.MethodsLeveraging publicly available omics datasets, we compared gene expression between healthy ovaries and those affected by PCOS through both bulk and single-cell analyses. Our approach focused on differential gene expression analysis, identification of distinct cell types and gene signatures in PCOS, construction of disease-specific gene expression modules, and mapping of cellular differentiation trajectories. Additionally, we examined the alterations in the immune microenvironment within PCOS to identify immune-related changes.ResultsOur analyses uncovered unique molecular signatures and immune modules in PCOS, characterized by differential gene expression, the presence of unique cell types, and altered pathways compared to healthy controls. Notably, we identified a significant role for Complement Component 3 (C3) in mediating these changes. Through gene intervention targeting C3 in granulosa cells and functional studies examining the effects of secreted C3 protein on H295R cells, Low level C3 mitigated inflammatory responses, while excess C3 proved detrimental to cell growth.ConclusionOur integrative omics analysis provides new insights into the molecular and immunological underpinnings of PCOS, highlighting the role of C3 in the disease’s pathogenesis. The identification of key molecular signatures and immune modules, including the involvement of C3, opens promising avenues for the development of novel diagnostic and therapeutic strategies for PCOS. These observations suggest that modulating C3 levels could have therapeutic implications for managing PCOS

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

An invasive species erodes the performance of coastal wetland protected areas

The world has increasingly relied on protected areas (PAs) to rescue highly valued ecosystems from human activities, but whether PAs will fare well with bioinvasions remains unknown. By analyzing three decades of seven of the largest coastal PAs in China, including World Natural Heritage and/or Wetlands of International Importance sites, we show that, although PAs are achieving success in rescuing iconic wetlands and critical shorebird habitats from once widespread reclamation, this success is counteracted by escalating plant invasions. Plant invasions were not only more extensive in PAs than non-PA controls but also undermined PA performance by, without human intervention, irreversibly replacing expansive native wetlands (primarily mudflats) and precluding successional formation of new native marshes. Exotic species are invading PAs globally. This study across large spatiotemporal scales highlights that the consequences of bioinvasions for humanity’s major conservation tool may be more profound, far reaching, and critical for management than currently recognized

Observation of whistler wave instability driven by temperature anisotropy of energetic electrons on EXL-50 spherical torus

Electromagnetic modes in the frequency range of 30-120MHz were observed in electron cyclotron wave (ECW) steady state plasmas on the ENN XuanLong-50 (EXL-50) spherical torus. These modes were found to have multiple bands of frequencies proportional to the Alfv\'en velocity. This indicates that the observed mode frequencies satisfy the dispersion relation of whistler waves. In addition, suppression of the whistler waves by the synergistic effect of Lower Hybrid Wave (LHW) and ECW was also observed. This suggests that the whistler waves were driven by temperature anisotropy of energetic electrons. These are the first such observations (not runaway discharge) made in magnetically confined toroidal plasmas and may have important implications for studying wave-particle interactions, RF wave current driver, and runaway electron control in future fusion devices

Effect of oregano essential oil on intestinal immunoglobulin G in Holstein dairy bulls

IntroductionImmunoglobulin G (IgG) is important in mediating humoral immunity and in the maintenance of immune homeostasis in the intestinal mucosa. Oregano essential oil (OEO) is a natural herbal extract that possesses antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. As the effects of OEO on intestinal mucosal immunity in Holstein dairy bulls remained unclear, we investigated the effect of dietary supplementation of OEO on IgG levels and IgG+ cells residing in the intestinal tract in Holstein dairy bulls.MethodsTwelve Holstein bulls in good health of approximately 10 months of age were selected for the experiment and randomly equally divided into two groups. The control (CK) group was fed a basal ration, and in the OEO group, the basal ration was supplemented with OEO (20 g/head/day). After 300 days of feeding, tissue samples of the jejunum, ileum, and colon of the bulls in each group were collected for histopathological analysis, immunohistochemistry, and enzyme-linked immunosorbent assays, respectively.ResultsThe jejunum, ileum, and colon of bulls in the CK group had obvious pathological damage, whereas the structure of each intestinal segment was clear and intact. In the OEO group, pathological damage was significantly reduced. IgG+ plasma cells were diffusely distributed in the lamina propria of the jejunum, ileum, and colon in the CK and OEO groups, with no significant difference between the groups. OEO supplementation significantly reduced the number of IgG+ plasma cells in each intestinal segment, with the highest decrease rate being noted for the ileum (22.87%), followed by the colon (19.45%) and jejunum (8.52%). ELISA test results and immunohistochemical results were mutually verified. The change in IgG content was consistent with the trend of change in the number of IgG+ plasma cells.DiscussionOur findings suggest that OEO supplementation does not alter the diffuse spatial distribution of IgG+ plasma cells in the intestines of Holstein dairy bulls, but lowers immunoglobulin levels to normal levels, significantly reduces intestinal damage, and may enhance mucosal immune defence barrier function by inhibiting inflammatory reactions

Comparative and functional genomics reveals genetic diversity and determinants of host specificity among reference strains and a large collection of Chinese isolates of the phytopathogen Xanthomonas campestris pv. campestris

Construction of a microarray based on the genome of Xanthomonas campestris pv.campestris (Xcc), and its use to analyse 18 other virulent Xcc strains, revealed insights into the genetic diversity and determinants of host specificity of Xcc strains

Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization

While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could neutralize ~30% of HIV-1 strains. To explore the ability of the murine immune system to generate cross-clade neutralizing antibodies and to investigate how higher breadth and potency might be achieved, we tested 17 prime-boost regimens that utilized diverse fusion peptide-carrier conjugates and HIV-1 envelope trimers with different fusion peptides. We observed priming in mice with fusion peptide-carrier conjugates of variable peptide length to elicit higher neutralizing responses, a result we confirmed in guinea pigs. From vaccinated mice, we isolated 21 antibodies, belonging to 4 distinct classes of fusion peptide-directed antibodies capable of cross-clade neutralization. Top antibodies from each class collectively neutralized over 50% of a 208-strain panel. Structural analyses - both X-ray and cryo-EM - revealed each antibody class to recognize a distinct conformation of fusion peptide and to have a binding pocket capable of accommodating diverse fusion peptides. Murine vaccinations can thus elicit diverse neutralizing antibodies, and altering peptide length during prime can improve the elicitation of cross-clade responses targeting the fusion peptide site of HIV-1 vulnerability

Solenoid-free current drive via ECRH in EXL-50 spherical torus plasmas

As a new spherical tokamak (ST) designed to simplify engineering requirements of a possible future fusion power source, the EXL-50 experiment features a low aspect ratio (A) vacuum vessel (VV), encircling a central post assembly containing the toroidal field coil conductors without a central solenoid. Multiple electron cyclotron resonance heating (ECRH) resonances are located within the VV to improve current drive effectiveness. Copious energetic electrons are produced and measured with hard X-ray detectors, carry the bulk of the plasma current ranging from 50kA to 150kA, which is maintained for more than 1s duration. It is observed that over one Ampere current can be maintained per Watt of ECRH power issued from the 28-GHz gyrotrons. The plasma current reaches Ip>80kA for high density (>5e18me-2) discharge with 150kW ECHR heating. An analysis was carried out combining reconstructed multi-fluid equilibrium, guiding-center orbits of energetic electrons, and resonant heating mechanisms. It is verified that in EXL-50 a broadly distributed current of energetic electrons creates smaller closed magnetic-flux surfaces of low aspect ratio that in turn confine the thermal plasma electrons and ions and participate in maintaining the equilibrium force-balance