A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events.

Sluggish and Ion-Resilient Behavior of Interfacial Aqueous Layer on Single-Layer Graphene Oxide: Insights from In Situ Atomic Force Microscopy.

Understanding interfacial interactions of graphene oxide (GO) is important to evaluate its colloidal behavior and environmental fate. Single-layer GO is the fundamental unit of GO colloids, and its interfacial aqueous layers critically dictate these interfacial interactions. However, conventional techniques like X-ray diffraction are limited to multilayer systems and are inapplicable to single-layer GO.

Bisphenols and brominated bisphenols induced endothelial dysfunction via its disruption of endothelial nitric oxide synthase.

Emerging literatures have concentrated on the association between cardiovascular diseases risk of typical endocrine disruptor bisphenols, which also put forward the further studies need respect to the potential mechanism. Herein, we investigated the endothelial dysfunction effects of bisphenols and brominated bisphenols involved in aortic pathological structure, endothelial nitric oxide synthase (eNOS) protein phosphorylation, synthase activity and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice. Bisphenol A (BPA) and bisphenol S (BPS) increased NO production by 85.

Revolutionizing Solid-State NASICON Sodium Batteries: Enhanced Ionic Conductivity Estimation through Multivariate Experimental Parameters Leveraging Machine Learning.

Na superionic conductor (NASICON) materials hold promise as solid-state electrolytes due to their wide electrochemical stability and chemical durability. However, their limited ionic conductivity hinders their integration into sodium-ion batteries. The conventional approach to electrolyte design struggles with comprehending the intricate interactions of factors impacting conductivity, encompassing synthesis parameters, structural characteristics, and electronic descriptors.

Long-Term Exposure of Graphene Oxide Suspension to Air Leading to Spontaneous Radical-Driven Degradation.

Understanding the environmental transformation and fate of graphene oxide (GO) is critical to estimate its engineering applications and ecological risks. While there have been numerous investigations on the physicochemical stability of GO in prolonged air-exposed solution, the potential generation of reactive radicals and their impact on the structure of GO remain unexplored. In this study, using liquid-PeakForce-mode atomic force microscopy and quadrupole time-of-flight mass spectroscopy, we report that prolonged exposure of GO to the solution leads to the generation of nanopores in the 2D network and may even cause the disintegration of its bulk structure into fragment molecules.

Associations between exposure to cadmium, lead, mercury and mixtures and women's infertility and long-term amenorrhea.

Background: Cadmium (Cd), lead (Pb), and mercury (Hg) have been shown to exhibit endocrine disrupting properties. Their effects on women's reproductive health, however, remain elusive. Here, we investigated associations between blood concentrations of Pb, Cd, Hg, and their mixture and infertility and long-term amenorrhea in women aged 20-49 years using the US National Health and Nutrition Examination Survey (NHANES) 2013-2018 cross-sectional survey.

Carcinogenic Risk of 2,6-Di--Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: , , and Investigations.

Thousands of contaminants are used worldwide and eventually released into the environment, presenting a challenge of health risk assessment. The identification of key toxic pathways and characterization of interactions with target biomacromolecules are essential for health risk assessments. The adverse outcome pathway (AOP) incorporates toxic mechanisms into health risk assessment by emphasizing the relationship among molecular initiating events (MIEs), key events (KEs), and adverse outcome (AO).

Benzophenone-1 induced aberrant proliferation and metastasis of ovarian cancer cells via activated ERα and Wnt/β-catenin signaling pathways.

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10-10 M) on estrogen receptor (ER) α-associated signaling pathways.

Endothelial barrier dysfunction induced by anthracene and its nitrated or oxygenated derivatives at environmentally relevant levels.

Polycyclic aromatic hydrocarbons (PAHs) are epidemiologically associated with cardiovascular diseases characterized by early key events involving in the disruption of endothelial barrier function. Whether PAHs can induce adverse cardiovascular outcome by directly destabilizing endothelial barrier function remains elusive. Herein, we investigated the effect of anthracene (ANT), 9-nitroanthracene (9-NANT), and 9,10-anthraquinone (9,10-AQ) on vascular endothelial barrier functions in human umbilical vein endothelial cells (HUVECs).

Transcriptome aberration in mice uterus associated with steroid hormone response and inflammation induced by dioxybenzone and its metabolites.

Benzophenone-type UV filters have been implicated in multiple adverse reproductive outcomes, yet the underlying processes and molecular targets on the female reproductive tract remain largely unknown. Herein, we investigated the effect of dioxybenzone, one of the widely used congeners, and its demethylated (M1) and hydroxylated (M2) metabolites on transcriptome profiles of ICR mice uterus and identified potential cellular targets in human endometrial stromal cells (HESCs) separated from normal endometrium tissues. Dioxybenzone, M1 and M2 (20 mg/kg bw/d) significantly induced transcriptome aberration with the induction of 683, 802, and 878 differentially expressed genes mainly involved in cancer, reproductive system disease and inflammatory disease.

2,6-Di-tert-butylphenol and its quinone metabolite trigger aberrant transcriptional responses in C57BL/6 mice liver.

2,6-Di-tert-butylphenol (2,6-DTBP) is used as an antioxidant with wide commercial applications and its residues have been detected in various environmental matrices. 2,6-DTBP may enter human body via ingestion, inhalation or other exposure pathways. However, its susceptibility to biotransformation and potential of the metabolic products to trigger aberrant transcriptional responses remain unclear.

Enhanced Disrupting Effect of Benzophenone-1 Chlorination Byproducts to the Androgen Receptor: Cell-Based Assays and Gaussian Accelerated Molecular Dynamics Simulations.

Benzophenone-1 (BP-1), one of the commonly used ultraviolet filters, has caused increasing public concern due to frequently detected residues in environmental and recreational waters. Its susceptibility to residual chlorine and the potential to subsequently trigger endocrine disruption remain unknown. We herein investigated the chlorination of BP-1 in swimming pool water and evaluated the endocrine disruption toward the human androgen receptor (AR).

Dioxybenzone triggers enhanced estrogenic effect via metabolic activation: in silico, in vitro and in vivo investigation.

Dioxybenzone is widely used in cosmetics and personal care products and frequently detected in multiple environmental media and human samples. However, the current understanding of the metabolic susceptibility of dioxybenzone and the potential endocrine disruption through its metabolites in mimicking human estrogens remains largely unclear. Here we investigated the in vitro metabolism of dioxybenzone, detected the residue of metabolites in rats, and determined the estrogenic disrupting effects of these metabolites toward estrogen receptor α (ERα).

Pentabromoethylbenzene Exposure Induces Transcriptome Aberration and Thyroid Dysfunction: , and Investigations.

Pentabromoethylbenzene (PBEB), as one of the novel brominated flame retardants (NFBRs), has caused increasing public concern for health risks. Till now, information regarding potential effects of PBEB on thyroid function remains unclear. Herein, we investigated thyroid disruption of PBEB and and evaluated thyroid dysfunction induced by PBEB using Sprague-Dawley rats.

Metabolic Susceptibility of 2-Chlorothioxanthone and Its Toxic Effects on mRNA and Protein Expression and Activities of Human CYP1A2 and CYP3A4 Enzymes.

Thioxanthones (TXs) are photoinitiators widely used in UV curable resins and food packaging, and their residues have been frequently detected in human bodies. Our current understanding of the susceptibility of residual TXs to metabolism and their effects on human health is very limited. The in vitro metabolism of TXs and its toxic effects on cytochrome P450 (CYP) (the key xenobiotic metabolizing enzymes) were examined in this study.

Thyroid Disruption by Bisphenol S Analogues via Thyroid Hormone Receptor β: in Vitro, in Vivo, and Molecular Dynamics Simulation Study.

Bisphenol S (4-hydroxyphenyl sulfone, BPS) is increasingly used as a bisphenol A (BPA) alternative. The global usage of BPS and its analogues (BPSs) resulted in the frequent detection of their residues in multiple environmental media. We investigated their potential endocrine-disrupting effects toward thyroid hormone receptor (TR) β.

Binding Specificity Determines the Cytochrome P450 3A4 Mediated Enantioselective Metabolism of Metconazole.

Cytochrome P450 3A4 (CYP3A4) is a promiscuous enzyme, mediating the biotransformations of ∼50% of clinically used drugs, many of which are chiral molecules. Probing the interactions between CYP3A4 and chiral chemicals is thus essential for the elucidation of molecular mechanisms of enantioselective metabolism. We developed a stepwise-restrained-molecular-dynamics (MD) method to model human CYP3A4 in a complex with cis-metconazole (MEZ) isomers and performed conventional MD simulations with a total simulation time of 2.

Side Chains of Parabens Modulate Antiandrogenic Activity: In Vitro and Molecular Docking Studies.

Parabens have been widely used in packaged foods, pharmaceuticals, and personal-care products. Considering their potential hydrolysis, we herein investigated structural features leading to the disruption of human androgen receptor (AR) and whether hydrolysis could alleviate such effects using the recombinant yeast two-hybrid assay. Parabens with an aryloxy side chain such as benzyl paraben and phenyl paraben have the strongest antiandrogenic activity.