Nitroaniline (NA) isomers are important, yet hazardous dye industry intermediates, require rapid and selective detection. Although conventional coordination polymers can detect NA through fluorescence quenching or wavelength shifting, however their limited signal discrimination often complicates the detection process. In this context, excited-state intramolecular proton transfer (ESIPT)-regulated emission switching offers distinct advantages by enabling dual-to-single emission transitions, visual color change, and improved analyte discrimination through the modulation of proton transfer pathways. Herein, an ESIPT-active Cd(II)-based coordination polymer has been synthesized using 2,5-dihydroxyterephthalate (dht) as an ESIPT-active ligand. The framework exhibits ESIPT-mediated dual emission in polar solvents, with the most pronounced response in water, producing intense yellow luminescence. Notably, exposure to aqueous solutions of NA isomers selectively perturbed the water-assisted ESIPT process, resulting in a distinct dual-to-single emission transition accompanied by fluorescence quenching and a readily noticeable visual color change from yellow to colorless. In contrast, other aromatic amines produced negligible disruption of the dual-emission response, highlighting the excellent selectivity of the sensing platform. Generalized-gradient-approximation-based DFT calculations by guest-induced modulation of competing proton-transfer pathways explain the observed ESIPT response. This study demonstrates that ESIPT-regulated dual-to-single emission switching can provide an advanced luminescent CP-based sensor for the selective detection and discrimination of nitroaniline isomers.

Three nonprofit organizations-ALS Therapy Development Institute (ALS TDI), Answer ALS, and the Critical Path Institute (C-Path)-collaborated to harmonize distinct ALS research datasets using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). This effort was designed to make otherwise separate ALS resources more comparable, enabling larger and more informative cross-cohort analyses. The teams coordinated vocabulary mapping, identified OMOP vocabulary gaps, and submitted new concepts to the Observational Health Data Science and Informatics (OHDSI) community for approval. Harmonized data from ALS TDI and Answer ALS were merged in the Neuromine data portal, while their clinical and digital health technology (DHT) datasets are also available through C-Path's Rare Disease Cures Accelerator-Data Analytics Platform (RDCA-DAP). This collaboration aligns with current regulatory priorities for data sharing and offers a model for harmonizing rare disease data. A robust, public GitHub repository was established to share real-time updates with the ALS research community.

Asthma is a chronic airway disease where androgens play a regulatory role. Dickkopf-1 (DKK1), a secreted glycoprotein, is positively correlated with androgens. This study aims to explore whether androgens upregulate DKK1 to inhibit Th2 response, potentially alleviating asthma. First, an asthma model was established using immunodeficient male mice. These mice were then divided into five groups and administered dihydrotestosterone (DHT) and/or the DKK-1 inhibitor WAY-262,611. Airway inflammation and lung tissue damage were assessed in each group. Furthermore, bronchoalveolar lavage fluid (BALF) inflammatory markers, the helper T cell 1/helper T cell 2 (Th1/Th2) ratio, and relevant parameters in serum and lung tissue were evaluated. Next, we established an asthma cell model using airway epithelial cells (BECs) and dust mites (HDM) stimulation. After treating with negative control (si-NC) and DKK1-targeted small interfering RNA (si-DKK1), five cell groups were established, with DHT treatment included. We assessed DHT's impact on DKK1 expression in BECs, then co-cultured these five cell groups with CD4[+] T cells to verify links to Th1/Th2-related factors. Firstly, the in vivo experiments showed that DHT attenuated asthma-induced lung damage and inflammation, reduced Th2's proportion, and normalized Th1/Th2 balance. Co-treatment with WAY-262,611 reversed DHT's protection impact. Subsequently, in vitro cell experiments confirmed that DHT suppressed Th2 response; siRNA-mediated DKK1 knockdown abrogated this suppression. Androgens promote the expression of DKK1 in BECs, thereby inhibiting Th2 response and ultimately improving asthma.

Gene Regulatory Networks (GRNs) are crucial for understanding cell fate decisions and disease mechanisms. However, inferring GRNs from single-cell RNA sequencing remains challenging due to noise, data sparsity, and species-specific distribution variations. We propose GP-DHT (Gene Pair-Dual Head Transformer), a single-cell GRN inference framework that pre-trains gene representations on a unified shared gene space using the BEELINE datasets of humans and mice. It models gene-cell expression relationships through a multi-relational heterograph and predicts transcription factor (TF)-target regulatory links using a dual-head Transformer. These two heads correspond to complementary task objectives: a classification head for regulatory link prediction and a projection head for gene pair-level supervised contrastive learning. This design enables the model to optimize both prediction accuracy and representation separability in a sparse single-cell setting. The human-mouse shared-gene stage is used to initialize expression-derived gene representations in a harmonized gene space. During dataset-wise supervised training, GenePairSupCon is applied within each training fold to regularize gene-pair representations, followed by fine-tuning and evaluation within each BEELINE dataset. To enhance reproducibility and interpretability, we further clarify the mapping of orthologous genes and gene symbol unification, TF-level data partitioning and leakage control, negative label sensitivity, and quantitative embedding quality assessment. Hard negative example experiments show that negative label construction has a substantial impact on task difficulty, while supervised contrastive learning significantly improves the separability of embeddings, as measured by Silhouette score, Davies-Bouldin index, Calinski-Harabasz score, and inter/intra distance ratio. GP-DHT can also recover prior-supported candidate regulatory modules and provide additional interpretable support through post-hoc pair-level attribution analysis on frozen predictors. In summary, these results support GP-DHT as a robust shared gene representation learning framework for dataset-level single-cell GRN prediction.

This study aimed to assess the structural response of the normal prostate during its recovery following dutasteride discontinuation, either abruptly or gradually, in short-term or long-term treated rats. Fifty-six adult male Wistar rats were randomly allocated into seven groups: a control group and two dutasteride-treated groups (for 4 or 8 weeks, 0.5 mg/kg/day, orally). Furthermore, each corresponding group of the 4- and 8-week groups was subjected to abrupt or tapered drug discontinuation. At the end, blood samples were withdrawn for testosterone (T) and dihydrotestosterone (DHT) analyses. Ventral prostates (VP) were resected and subjected to hematoxylin and eosin (H&E) and Masson trichrome (MTC) staining. Besides, polymerase chain reaction (PCR) analysis and immunohistochemical identification of proliferating cell nuclear antigen (PCNA), caspase-3, and androgen receptors (AR) were performed. After 4 and 8 weeks of treatment, VP showed acinar trophic changes with reduced epithelial thickness in H&E, increased Masson-stained collagen distribution area, suppression of proliferation marker PCNA, activation of apoptosis, and AR downregulation. Discontinuation of dutasteride, whether abruptly or gradually, after short-term treatment showed prostate re-expansion and proliferation in both designs of withdrawal. However, in long-term dutasteride-treated rats, tapered discontinuation maintained the attained atrophic changes provoked in the prostate versus abrupt discontinuation. Abrupt discontinuation was associated with enhanced AR expression coupled with prostate proliferation and caspase-3 downregulation, leading to marked prostate rebound. As a preclinical study, it was concluded that the duration of exposure and the discontinuation design, whether abrupt or tapered, were found to have an impact on the prostate's recovery following dutasteride cessation. Abrupt discontinuation was linked to structural prostate rebound, which may be explained by AR upregulation.

Abuse of Anabolic-Androgenic Steroids (AAS) by professional and recreational athletes for endurance performance and physique is increasing globally, consequently resulting in secondary pathophysiological effects. The present investigation aims to determine the effect of one of the AAS, stanozolol (ST), on uterine physiology and histology. A total of 15 female mice were assigned to three experimental groups (n = 5). ST was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/kg bwt or 1% alcohol-baseline control) for 30 days, and treatment was withdrawn on the 31st day. In this study, we evaluated histomorphometry of the uterus, immunoexpression of the estrogen receptor α (ERα), the androgen receptor (AR), and the prolactin receptor (PRLR), after ST treatment. In addition, we measured serum levels of testosterone (T), estradiol (E2), and prolactin (PRL). Morphometric evaluation of uterus demonstrated aberrant endometrial luminal epithelial proliferation, marked by irregular branching with papillary formations. Prolonged administration of ST resulted in disruption of uterine organization, reflecting its deleterious impact on uterine histoarchitecture. In the high-dose treated group, divergent ERα immunoexpression-characterized by endometrial downregulation and myometrial upregulation-correlated with increased myometrial thickness and subsequent hyperplasia. ST, being a derivative of Dihydrotestosterone (DHT), an anabolic steroid, may exert its androgenic-to-enhanced anabolic efficacy through non-genomic actions in the myometrium, while inducing distinct pathologic changes in the endometrium, suggesting a compartment-specific effect in the murine uterus. Prolonged treatment of ST augmented stromal immunoexpression of AR in the endometrium, suggesting AR-dependent mechanisms in this compartment. Substantial hyperexpression of prolactin receptor (PRLR) in both endometrium and myometrium suggests a potential stimulatory effect of ST on PRLR. High-dose ST administration significantly elevated circulating T and PRL levels while suppressing E2 concentrations, indicating interference with the hypothalamic-pituitary-gonadal (HPG) axis, reflecting an altered hormonal milieu. It is inferred that prolonged treatment of ST resulted in aberrant endometrial proliferation, histoarchitectural anomalies, compartment-specific differential immunoexpression of hormone receptors in the endometrium and myometrium, and altered serum hormonal milieu.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine and metabolic disorder whose etiology has not yet been fully elucidated. Emerging research has revealed an association between PCOS pathogenesis and post-translational modifications of proteins. However, the effect of neddylation on PCOS pathogenesis has not been investigated. In this study, key proteins of the neddylation pathway (Nedd8, neddylation-activating enzyme (NAE), and Cullin-1/2/3) were significantly upregulated in the granulosa cells of patients with PCOS; this was accompanied by enhanced apoptosis (increased Bax and Caspase-3, decreased Bcl-2) and elevated expression of the androgen synthesis-related proteins, namely: androgen receptor (AR) and Cytochrome P450 Family 17 Subfamily A Member 1(CYP17A1). In the in vitro DHT-induced PCOS KGN cell model, key neddylation pathway proteins (Nedd8, NAE, and Cullin-1) were upregulated. Overexpression of Nedd8 and inhibition of neddylation by MLN4924 promoted apoptosis. However, inhibition of neddylation by MLN4924 reversed AR/CYP17A1 protein expression. In a rat model of PCOS, MLN4924 treatment significantly suppressed the expression of Nedd8, NAE, and Cullin-1/2/3 in the ovarian tissue, restored estrous cycles, alleviated ovarian morphological abnormalities (characterized by increased corpora lutea and reduced cystic follicles), and decreased serum testosterone and LH levels. MLN4924 significantly promoted ovarian granulosa cell apoptosis, but reduced the expression of androgen synthesis-related proteins. Together, these findings indicate the unrecognized role of neddylation in PCOS, while highlighting that MLN4924 represents a potential therapeutic approach for PCOS treatment.

Androgenetic alopecia (AGA) is a progressive hair disorder with a substantial psychosocial impact. Current therapies have variable efficacy and adherence challenges. Exosomes are emerging as regenerative candidates. We systematically appraised preclinical (in vivo / in vitro) evidence on exosome-based intervention for AGA following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searching PubMed and Scopus. Eligible studies evaluated exosome or extracellular vesicle interventions in androgen-related alopecia models. Of 352 records, 16 studies met inclusion criteria, most employing male C57BL/6 mice with testosterone or dihydrotestosterone (DHT) induction alongside assays in dermal papilla cells (DPCs) and hair follicle stem cells. Sources include mesenchymal stem cell derived, DPC-derived, platelet-rich plasma derived, and engineered/primed exosomes, predominantly delivered via local intradermal/subcutaneous routes or topical microneedles/hydrogels over 2 to 4 weeks. Across studies, exosomes improved hair coverage and density, anagen/telogen ratio, follicle diameter, dermal thickness, and proliferation markers, while reducing apoptosis; mechanistic signals consistently showed reactivation of Wnt/β-catenin and down-modulation of TGF-β/SMAD3, with additional angiogenic support, anti-inflammatory effects, and mitigation of oxidative stress, and adverse signals were minimal in animals. Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) appraisal indicated generally low risk with common concerns regarding blinding and allocation concealment. Overall, exosome therapy demonstrates compelling preclinical efficacy for AGA via multi-target regenerative mechanisms.

The testicular functions of neuropeptide Y are largely unexplored in non-mammalian vertebrates as the few reports available remain restricted to fishes. Current research work reveals the testicular presence of npy and npyr in Hemidactylus flaviviridis and its variation in expression depending upon reproductive phases, marking the first documentation of such findings in reptilian species. Expression analysis of npy/npyr across different reproductive phases showed peak levels of both ligand and receptor during the recrudescent period, while the lowest expression occurred in regression. The investigation also examined the influence of NPY on markers of testicular spermatogenesis and steroidogenesis in H. flaviviridis. The in vitro exposure of wall lizard testes to NPY during recrudescent phase stimulated bcl2, while simultaneously reduced caspase-3. NPY treatment also stimulated testicular expression of scf, c-kit, pcna, bmp-15 and gdf-9, along with gonadotropin receptor (fshr), and sex-steroid receptors (er-α, er-β, and ar). Further, NPY elevated star expression and promoted testosterone synthesis in wall lizard. Regarding the regulation of testicular npy and its receptor, npyr the expression of both ligand and its receptor was upregulated by the neuropeptide, kisspeptin, adipokines like leptin and nesfatin-1, and sex steroids such as DHT, and E2, while they were suppressed by the gonadotropin, FSH and the neuropeptide, substance P. Overall, this investigation provides a detailed documentation of the presence, phase-specific pattern of expression, role, and hormonal regulation of NPY and its receptor in wall lizard testes.