IL2RG knockout mitigates polycystic ovary syndrome pathogenesis by transitioning pyroptosis to apoptosis through the GSDME pathway.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear.

Results: The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects.

Gas detection based on a mid-infrared super-pixel multi-spectral imaging device.

Gas detection is an important application area in industry. The detection of plays a crucial role in environmental protection. However, the primary challenges in achieving atmospheric and other detection of other gases revolve around developing instrumentation featuring a broad detection range, heightened sensitivity, and dynamic real-time capabilities.

Microglial States Are Susceptible to Senescence and Cholesterol Dysregulation in Alzheimer's Disease.

Cellular senescence is a major contributor to aging-related degenerative diseases, including Alzheimer's disease (AD), but much less is known about the key cell types and pathways driving senescence mechanisms in the brain. We hypothesized that dysregulated cholesterol metabolism is central to cellular senescence in AD. We analyzed single-cell RNA-seq data from the ROSMAP and SEA-AD cohorts to uncover cell type-specific senescence pathologies.

An efficient and precise solution-vacuum hybrid batch fabrication of 2D/3D perovskite submodules.

The quickly processable solution deposition and accurately controllable vacuum deposition are the two competing mainstream fabrication techniques for perovskite films. However, the former may inevitably leave pinholes on film surface and calls for further treatment, the latter exhibits a generally low processing rate. In this work, we develop a solution-vacuum hybrid batch fabrication to precisely deposit nanoscale two-dimensional (2D) capping layer via all-vacuum evaporation on a solution-deposited three-dimensional bulk film.

Significant enhancement of inhibitory strength of bisphenol A analogs against human and rat 5α-reductase 1 upon halogenation of the benzene ring: Potentially disrupting neurosteroid biosynthesis.

Bisphenol A (BPA) halogenation derivatives, formed via radical or electrophilic substitution, constitute a class of emerging contaminants, with brominated variants dominating the flame-retardant market. Their effect on steroid 5α-reductase 1 (SRD5A1) activity in neural and testicular cells remains unclear. This study examined inhibitory effects of seven BPA analogs on SRD5A1, focusing on dihydrotestosterone synthesis.

Isothiazolinone biocides as aromatase inhibitors: Hormonal disruption, and in silico docking and SAR/QSAR analysis.

Isothiazolinone biocides, widely used in industrial, agricultural, and biomedical applications due to their unique chemical properties, have unclear effects on CYP19A1 (aromatase), a critical enzyme in placental estrogen synthesis. This study systematically assessed seven isothiazolinone biocides for their inhibitory effects on human and rat CYP19A1. Dichlorooctylisothiazolinone emerged as the most potent inhibitor, with IC values of 5.

Dexmedetomidine preserves neuronal function by promoting mitochondrial biogenesis through the AMPK/PGC-1α pathway.

Mitochondrial dysfunction, often linked to the deregulation of mitochondrial biogenesis, plays a significant role in the progression of neurological diseases. Dexmedetomidine (Dex), a selective alpha-2 adrenergic agonist utilized for anesthesia and sedation, has a largely unexplored impact on mitochondrial function. In this study, cells were treated with Dex at concentrations of 10 μg/mL and 20 μg/mL.

Real-time super-resolution structured illumination microscopy: current progress in joint space and frequency reconstruction.

Due to its low light dose, ultra-high imaging speed and super-resolution, structured illumination microscopy (SIM) is now widely used in various applications to study dynamic interactions between intracellular structures of living cells. However, real-time imaging remains challenging due to the limitations of existing reconstruction algorithms, such as spatial frequency domain conversion, iterative parameter estimation, and complex deconvolution. To achieve "what you see is what you get", the reconstruction algorithm of SIM needs to be improved.

Organotins as inhibitors targeting human and rat steroid 5α-reductase 1: structure-activity relationship and docking analysis.

Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone, playing crucial roles in steroidogenesis in the brain and reproductive system. This study aimed to systematically evaluate the inhibitory effects and mechanisms of action of organotins on human and rat SRD5A1. Sixteen organotins were screened for the inhibitory strength and enzyme inhibition assays, molecular docking, and correlation analyses were performed.

Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by salicylate preservatives: 3D quantitative structure-activity relationship and in silico docking analysis.

The placenta contains 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), an enzyme critical for converting estrone to estradiol. Salicylates, widely used as preservatives, may inhibit 17β-HSD1, but their inhibitory strength and structure-activity relationships (SAR) remain unclear. This study evaluated 13 structurally diverse salicylates, identifying potent inhibitors of human and rat 17β-HSD1.

Isothiazole Disinfectants Inhibit Neurosteroid Production by Targeting Human and Rat 5α-Reductase Type 1.

Isothiazole disinfectants are widely used antimicrobial preservatives found in various consumer products, raising concerns about their potential effects on human health. This study investigated the inhibitory effects of seven isothiazole disinfectants on human and rat steroid 5α-reductase type 1 (SRD5A1), a key enzyme in neurosteroid biosynthesis. Among the tested compounds, dichlorooctylisothiazole exhibited the strongest suppression on human SRD5A1 with an IC value of 3.

Wave vector filter based on surface and Tamm plasmon polaritons.

This study proposes a wave vector filter leveraging coupling-induced transparency (CIT) between surface plasmon polaritons (SPPs) and Tamm plasmon polaritons (TPPs) to enable simultaneous wavelength and incident-angle selection, overcoming conventional optical filters' inability to control both parameters. By synergizing the wave vector selectivity of SPPs with the low-loss field enhancement of TPPs, the device achieves efficient spectral-angular filtering in the short-wave infrared regime. Structural optimization of silver gratings and Ag/distributed Bragg reflector (DBR) layers yields a 60% transmission peak at 2.

Halogen Atoms in Bisphenol A Derivatives Enhance the Inhibitory Potency against Human and Rat Placental 3β-Hydroxysteroid Dehydrogenases.

Halogenated bisphenol A (BPA) derivatives are extensively utilized in industrial production and have been detected in the environment, as well as in human samples. The 3β-HSDs are important for the catalytic transformation of pregnenolone into progesterone. But inhibition by BPA derivatives on 3β-HSD activity is still unclear.

Azole fungicides: Potential endocrine disrupting effects and impact on placental steroidogenesis via inhibiting human and rat 3β-hydroxysteroid dehydrogenase.

Azole fungicides disrupt pregnancy, but their effects on placental 3β-hydroxysteroid dehydrogenases (3β-HSDs) and structure-activity relationships (SARs) remain unclear. This study evaluated 9 azole fungicides for their inhibitory potency, mechanism, SAR, and docking interactions with human 3β-HSD1 and rat 3β-HSD4. Bromuconazole, climbazole, cyproconazole, and etaconazole inhibited human 3β-HSD1 (IC = 6.

Inhibition of brain human steroid 5α-reductase 1 by dithiocarbamates: A Comprehensive enzymatic and structural analysis.

We investigated the inhibitory effects of dithiocarbamates (DTCs) on human steroid 5α-reductase 1 (SRD5A1), an enzyme crucial for the conversion of testosterone or pregnenolone into neuroactive steroids. Utilizing a comprehensive approach that included enzyme assays, molecular docking simulations, and both structure-activity relationship (SAR) and 3D quantitative SAR (3D-QSAR) analyses, we assessed the potency and interaction mechanisms of DTCs with SRD5A1 in human SF126 cells. Our results demonstrated that zinc dibutyldithiocarbamate, disulfiram, ferbam, thiram, and ziram displayed significant inhibitory activity against SRD5A1, with IC values of 1.

Structure activity relationship of Aristolochic acid analogues: Inhibitory effect on human and rat gonadal 3β-Hydroxysteroid dehydrogenases.

Aristolochia species have been used in traditional Chinese medicine for over 1500 years to treat gynecological disorders. Recent pharmacological efforts focus on developing safer aristolochic acid derivatives (AAs) to retain therapeutic efficacy while minimizing toxicity. Human 3β-hydroxysteroid dehydrogenase 2 (h3β-HSD2) catalyzes the formation of precursors for sex hormones and corticosteroids, which play critical role in endocrine disorders such as polycystic ovary syndrome (PCOS) and Cushing's syndrome.

Bisphenol Z inhibits the function of Leydig cells via upregulation of METTL3 expression in adult male rats.

The use of bisphenol A has been restricted due to its toxicity. However, the impact of its substitute, bisphenol Z (BPZ), on Leydig cell function remains uncertain. We aimed to examine the associations between BPZ exposure and the disruption of Leydig cell function via upregulating Mettl3 and inducing oxidative stress.

Asymmetric 1,4-Addition and Functionalization Strategy in Total Synthesis.

The transition-metal catalyzed enantioselective 1,4-addition and subsequent functionalization strategy provides a powerful approach to construct 2,3-disubstituted cycloalkanones, which are further utilized as important intermediates in the total synthesis of natural products. This concept article highlights recent advances in the methodology development and related synthetic applications.

High-Strength Conductive Hydrogel Fiber Prepared Via Microfluidic Technology for Functionalized Strain Sensing.

The rapid advancement of wearable flexible electronics has heightened the demand for hydrogel materials that combine mechanical robustness with electrical conductivity. Herein, the TEMPO-oxidized cellulose nanofibers-Graphene nanosheets/poly(vinyl alcohol)-sodium alginate-tannic acid (TOCN-GN/PVA-SA-TA, TGG) composite hydrogel fibers are prepared by microfluidic spinning technology to solve the bottleneck problems of poor dispersion of GN and imbalance of mechanical-conductive properties of traditional hydrogels. TOCN, acting as a biotemplate, effectively inhibits GN agglomeration via hydrogen bonding and mechanical interlocking, thereby enhancing GN dispersion and facilitating the formation of 3D conductive networks within hydrogel fibers.

Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by isothiazolinone-based disinfectants: Insights into mechanism and implications for hormonal homeostasis.

Isothiazolinone disinfectants constitute a class of broad-spectrum antimicrobial agents due to the pandemic of COVID-19. The aim of this study was to assess the impacts of six distinct isothiazolinone disinfectants on the activity of 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) in humans and rats, as well as on BeWo cells. We identified IC with 4,5-dichloro-2-octyl-1,2-thiazol-3-one exhibiting the most potent inhibition (8.

Impact of isothiazolinone biocides on gonadal steroid production: Focus on 3β-hydroxysteroid dehydrogenase inhibition.

Isothiazolinone biocides have been widely used as disinfectants during the COVID-19 pandemic. However, their effects on gonadal steroidogenesis remain unclear. This study investigated the endocrine-disrupting potential of isothiazolinone biocides, focusing on their inhibition of gonadal 3β-hydroxysteroid dehydrogenases (3β-HSDs).

In situ dual-activated NIRF/PA carrier-free nanoprobe for diagnosis and treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease threatening the life of millions people worldwide. Oxidative stress, mitochondrial dysfunction, and neuroinflammation are the pivotal causative elements of PD. Precise diagnosis enables timely monitoring initiation and progression of PD, thereby facilitating the formulation of customized and targeted treatment strategies.

Evidence for cPLA2 activation in Alzheimer's Disease Synaptic Pathology.

Background: Synapses are essential for learning and memory, and their loss predicts cognitive decline in Alzheimer's disease (AD). Synaptic loss is associated with excitotoxicity, neuroinflammation, amyloid-β, and tau pathology, but the molecular mechanisms remain unclear. There is an urgent need to identify new targets to modify the disease and slow synaptic loss and cognitive decline.

Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy.

The development of effective and broad-spectrum antiviral therapies remains an unmet need. Current virus-targeted antiviral strategies are often limited by narrow spectrum of activity and the rapid emergence of resistance. As a result, there is increasing interest in alternative approaches that target host cell factors critical for viral replication.

Placental mesenchymal stem cell-derived exosomes treat endometrial injury in a rat model of intrauterine adhesions.

Intrauterine adhesion (IUA) refer to persistent inflammation and fibrosis due to damaged or infected endometrium and eventually lead to dysfunction. This study aimed to explore the therapeutic effects of exosomes (Exos) derived from placental mesenchymal stem cells (PMSCs) on endometrial repair in a rat model of IUA and to elucidate the underlying molecular mechanisms. PMSCs were characterized using flow cytometry and differentiation assays (osteogenic, adipogenic, and chondrogenic).