Search Results (482)

Background: Two natural steroids derived from cholesterol pathways are testosterone and progesterone, androgen and antiandrogen receptor binding. Steroid androgen antagonists can be prescribed to treat an array of diseases and disorders such as gender dysphoria. In men, androgen antagonists are frequently used to treat prostate cancer and hyperplasia. Sex hormones regulate the expression of the viral receptors in COVID-19 progression, and these hormones may act as a metabolic signal-mediating response to changes in glucose and Reactive Oxygen Species (ROS). The objective of the present study is to use artificial intelligence (AI) applications in healthcare to predict the targets and to assess biological assays of novel steroid derivatives prepared in house from the commercially available 16-dehydropregnenolone acetate (DPA^®) aimed at achieving the metabolic stability of glucose and steroid brain homeostasis. This suggests the introduction of aromatic or aliphatic structures in the steroid B-ring and D-ring. This is important since the roles of 5α-reductase and ROS in brain control of glucose and novel steroids homeostasis remain unclear. Methods: A tool prediction was used as a tuned algorithm, with the novel steroid derivatives data in web interface to carry out their pharmacological evaluation. The new steroidal derivatives were determined with neuroprotection effect using the select biomarkers of oxidative stress on induced hypoglycemic male rat brain and liver. The enzyme kinetics was established by the inhibition of the 5α-reductase enzyme on the brain myelin. Results: We used novel chemical structures to order the information of a Swiss data bank that allow target predictions. Biological assays suggest that steroid derivatives with an electrophilic center can interact more efficiently with the 5α-reductase enzyme, and by this way, induce neuroprotection in hypoglycemia model. All compounds were synthesized with a yield of 30–80% and evaluated with tool target prediction to understand the molecular mechanisms underlying a given phenotype or bioactivity and to rationalize possible favorable or unfavorable side effects, as well as to predict off-targets of known molecules and to clear the way for drug repurposing. Apart, they turned out to be good inhibitors for the 5α-reductase enzyme. Conclusions: The probed efficacy of these novel steroids with respect to spironolactone control appears to be a promising compound for future hormonal therapy with neuroprotection activity in glucose disorder status. However, further research with clinically meaningful endpoints is needed to optimize the use of androgen antagonists in these hormonal therapies in COVID-19 progression. Full article

Background/Objectives: Hypertension is a major modifiable risk factor for cardiovascular disease and may negatively affect muscle strength through vascular and metabolic mechanisms. Nevertheless, reference values for respiratory muscle strength (RMS) in hypertensive adults remain unavailable. This study aimed to establish sex- and age-specific reference values for maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in Brazilian adults with hypertension and to investigate clinical factors associated with these measures. Methods: This cross-sectional study included 234 hypertensive adults (109 women and 125 men; 30–80 years) enrolled in a cardiovascular rehabilitation program. Anthropometric, hemodynamic, and clinical data were collected. RMS was assessed using standardized procedures for MIP and MEP with an analog manovacuometer (−300 to +300 cmH₂O). Participants were stratified by age and sex. Statistical analyses included the Mann–Whitney U and Kruskal–Wallis tests and multivariate linear regression (p < 0.05). Results: Men exhibited significantly higher MIP and MEP values than women across most age groups. RMS declined progressively with age, with a more marked reduction after 60 years. MIP was identified as the primary predictor of MEP in both sexes, with higher coefficients of determination in men. The reference values obtained were largely comparable to those reported for healthy individuals. Conclusions: This study provides clinically relevant reference values for RMS Brazilian individuals with hypertension, offering useful parameters for respiratory assessment and individualized rehabilitation strategies. Full article

Introduction and Objectives: The thickness of the plantar fat pad (PFP) beneath the metatarsal heads may play a protective role in preventing forefoot disorders such as metatarsalgia. However, reference values for plantar adipose tissue thickness in this region among healthy individuals are currently unavailable. Therefore, the aim of this study was to determine, by means of ultrasound imaging, the thickness of the PFP beneath the five metatarsal heads and to analyze its possible relationship with body mass index (BMI). Materials and Methods: Thirty-five young adults (17 males and 18 females) with neutral feet, free from deformities or pain, participated in the study. Using a VINNO E35 ultrasound device, the thickness of the PFP beneath each of the five metatarsal heads was quantified. A linear transducer was positioned longitudinally along the axis of each metatarsal. The distance between the dermis and the flexor tendon was measured from the second to the fifth metatarsal heads, and from the fibular sesamoid for the first metatarsal head. Results: The central forefoot showed the greatest PFP thickness (2nd metatarsal head, 7.1 ± 0.9 mm; 3rd metatarsal head, 6.9 ± 0.9 mm). No significant differences in PFP thickness were found between sexes. However, a positive correlation was observed between BMI and PFP thickness at the fourth metatarsal head (r = 0.358, p = 0.035). Conclusions: The study demonstrated greater PFP thickness beneath the second and third metatarsal heads, with no significant sex-related differences. These findings indicate a consistent anatomical pattern independent of sex in young, healthy individuals. Moreover, a moderate influence of BMI was identified at the fourth metatarsal head, which could represent a potential protective mechanism against forefoot overload. Full article

The red swamp crayfish (Procambarus clarkii) is a globally important freshwater crustacean that exhibits pronounced sexual dimorphism, with males growing faster than females. However, the molecular mechanisms underlying sex differentiation in crustaceans remain poorly understood. In this study, Oxford Nanopore-based Direct RNA Sequencing (DRS) was employed to analyze the gonadal transcriptomes of male and female P. clarkii, identifying 20,001 previously unannotated genes and revealing extensive sex-specific differences in transcript structure, alternative splicing, and RNA modifications. Ovarian transcripts had shorter poly(A) tails and more frequent alternative splicing, while male gonads showed greater enrichment of m⁶A and psU modifications in the 3′ UTRs. qPCR validation confirmed the sex-biased expression of key candidate genes, including Dmrt7, FR, Fruitless, IAGBP, RDH, and Vtg. Collectively, these findings provide the first comprehensive epitranscriptomic landscape of P. clarkii gonads, underscoring the pivotal role of post-transcriptional regulation in sex determination and offering valuable insights for mono-sex breeding strategies in aquaculture. Full article

In sturgeon aquaculture, all-female production is desirable due to the high value of caviar. Genetic sexing and the production of WW superfemales are important steps toward achieving this. In this study, we identified the WSR and ZSR primers for amplification of W- and Z-specific regions, respectively. WSR primers were designed on the gene W-linked RT RNase H-like domain containing protein (rnhW). The polymerase chain reaction (PCR) bands were obtained with the WSR primer only in phenotypic female sturgeons, indicating that stable genetic sexing was achieved in most species, including those captured around Hokkaido. Moreover, rnhW showed female-specific expression in the gonads during early sex differentiation in kaluga and Amur sturgeon. ZSR primers were developed from the orofacial cleft 1 candidate gene 1 protein homolog. Clear and distinct gel band patterns for ZZ, ZW, and WW genotypes were obtained using WSR and ZSR primers, consistent with genotypic estimations by quantitative PCR. This consistency confirmed the presence of WW superfemales among offspring produced by fertilizing ZW females with ZW pseudomales masculinized using 17α-methyltestosterone. Our findings provide new insights into the mechanisms of sex determination and differentiation in sturgeons, bringing the establishment of an all-female production system within reach. Full article

Background/Objectives: The larval stage plays a pivotal role in determining caste and sex in Apis mellifera. This study integrates RNA-seq, WGCNA, and alternative splicing analyses to explore gene expression differences among 2-day-old worker, drone, and queen larvae. Methods: RNA-seq was conducted on 2-day-old larvae from all three castes. Differential expression, WGCNA, and alternative splicing patterns were investigated. A deep learning TCN model was trained using WGCNA-derived modules and demonstrated high classification accuracy. Results: The TCN model highlighted a top-10 gene set, including PDHB, Fibroin3, and LOC724161. Significant caste- and sex-specific splicing events were detected in Tk, Csd, and Fem, with AF events being most prevalent. Splicing differences between sexes exceeded those observed among castes. Conclusions: The 2-day-old larval stage is crucial for both caste and sex differentiation in honeybees. This study identifies key genes and splicing events, offering new insights into the molecular mechanisms underlying caste formation and sex determination. Full article

Cardiometabolic phenotypes such as obesity and impaired insulin action are key determinants of type 2 diabetes (T2D). Growing evidence highlights the postprandial state as a critical window in metabolic regulation, where epigenetic mechanisms, particularly DNA methylation in insulin-sensitive tissues, may play pivotal roles. However, their dynamics across prandial states in subcutaneous adipose tissue (SAT) remain unclear. We analyzed genome-wide DNA methylation in paired fasting and postprandial SAT biopsies from 29 asymptomatic, drug-naïve individuals classified as controls (n = 8), prediabetes n = 9), or T2D (n = 12). Postprandial samples followed a standardized mixed-meal test. DNA methylation was quantified using the Illumina MethylationEPIC array and analyzed through the Chip Analysis Methylation Pipeline (ChAMP) pipeline. Differential methylation was more pronounced postprandially, especially in the T2D group. After adjusting for age and sex, 4599 differentially methylated CpG sites (DMCs) were identified, with increased hypermethylation in T2D. A total of 130 DMCs across 99 genes, including LCLAT1, HLA-C, ZNF714, and HOOK2, were shared by prediabetes and T2D groups. Over-representation analysis revealed 202 enriched pathways related to insulin resistance, AMPK signaling, and immune responses. Additionally, 110 Differentially Methylated Regions (DMRs), including ZNF577 and AGPAT1, were detected. These findings reveal early, prandial-dependent epigenetic alterations in SAT that precede overt dysglycemia, offering insights into personalized prevention in T2D. Full article

Advances in next-generation sequencing have significantly improved the molecular diagnosis of mitochondrial diseases (MDs), a group of heterogeneous neurogenetic disorders. However, progress in understanding their pathogenic mechanisms and translating this knowledge into effective therapies remains limited. Elucidating the molecular determinants of phenotypic variability in primary MDs is essential to uncover disease mechanisms and identify novel therapeutic targets. We investigated a cohort of eight adult patients with genetically confirmed Progressive External Ophthalmoplegia (PEO)—an extremely rare mitochondrial disorder—and compared them with eight age- and sex-matched healthy controls. A comprehensive multi-omics approach combining LC–MS/MS-based proteomics, UPLC–MS/MS-based metabolomics, ATR–FTIR spectroscopy, and chemometric multivariate analysis was employed to identify molecular alterations associated with mitochondrial dysfunction. Distinct proteomic and metabolic patterns related to energy metabolism were observed in PEO patients, correlating with their genetic background. Metabolomic analysis showed altered amino acid levels (seven statistically relevant) and disruptions in the metabolism of cysteine, methionine, and glutathione; proteomics finding (154 differentially expressed proteins) revealed dysregulation in extracellular matrix (ECM) organization and immune response pathways. This integrative analytical strategy offers new insights into the molecular complexity of PEO and mitochondrial disorders. The identification of disease-associated molecular signatures may enhance the understanding of pathogenic mechanisms and support the development of improved diagnostic and therapeutic approaches for MDs. Full article

Raptors wintering in temperate regions face strong energetic constraints due to low temperatures and limited prey availability. Understanding how intrinsic traits and environmental conditions shape hunting performance helps to clarify the mechanisms underlying winter foraging efficiency. We studied wintering Hen Harriers (Circus cyaneus) in Austria over five consecutive winters (2020/21–2024/25) to quantify touchdown attempt rate and outcome in relation to sex, age, territorial status, and weather. Using generalized linear mixed models, we analyzed 1829 recorded touchdowns with individual identity as a random effect. Territorial females showed slightly higher attempt rates than males, whereas non-territorial females exhibited a tendency toward lower touchdown success. Adult males achieved the highest per-attempt efficiency, but age alone had no significant effect. Touchdown outcomes improved under cloud cover and declined with wind speed, while temperature showed no influence. Attempt rate was unaffected by any environmental variable. These results demonstrate that both intrinsic and extrinsic factors jointly determine winter foraging performance: males, with their smaller body size and agility, can persist even in vole-poor habitats by compensating through efficient flight and prey capture; territorial females benefit from stable access to vole-rich patches; and non-territorial females remain constrained by competition and limited access to prey. The findings highlight the need to maintain open farmland and vole-rich habitat to support diverse overwintering strategies. Full article

Background: Clear aligner therapy (CAT) represents a biomimetic orthodontic approach that uses flexible thermoplastic materials to reproduce the physiological tooth movement and mechanical load distribution of natural tissues. While these materials promote oral hygiene and aesthetic comfort, their long-term biological impact on the caries process remains uncertain. This retrospective study aimed to evaluate changes in the number of decayed teeth (ΔD) before and after clear aligner treatment and to identify duration-dependent risk factors. Methods: This retrospective study included 362 patients (279 females, 83 males) treated with Invisalign^® aligners between 2020 and 2024. Baseline and post-treatment panoramic radiographs were analyzed to determine decayed tooth counts. Age, sex, and total aligner count were recorded. Non-parametric tests, multivariable regression, and ROC analysis were used to assess predictors of ΔD. Results: The mean number of decayed teeth increased slightly from 3.54 ± 2.76 to 3.83 ± 2.93 (p < 0.001). Longer treatment duration was independently associated with caries progression (β = +0.0088 per tray, p = 0.0037), and each 10-tray increment increased the odds of new decay by 55% (OR = 1.55, 95% CI: 1.26–1.90). ROC analysis identified ≥42 trays as a clinically relevant threshold (AUC = 0.67). Conclusions: Clear aligner therapy demonstrated a statistically significant yet clinically small increase in caries incidence, primarily related to treatment duration. As a biomimetic orthodontic approach that integrates mechanical and biological dynamics, extended clear aligner use may alter biofilm–surface interactions and salivary conditions over time. Therefore, preventive strategies–such as professional fluoride applications, strict cleaning protocols, and shorter recall intervals–should be emphasized for long-duration treatments to preserve the biological benefits of this biomimetic system. Full article

Intersex people continue to face barriers in healthcare. Despite notable ethical and legal advances, the role of socio-cognitive factors influencing clinical decision-making remains insufficiently understood. Critical perspectives call for revising the epistemological and normative foundations of medical practice, as clinical judgments may still be shaped by professionals’ beliefs and limited access to accurate information. Objective: This study examined how levels of knowledge, beliefs about gender determinism, and adherence to gender roles influence healthcare professionals’ attitudes toward intersex people. Methods: A total of 210 healthcare professionals from Spain participated in a cross-sectional survey. Participants completed the Intersex Knowledge Questionnaire, the short version of the Bem Sex-Role Inventory, and the Gender Determinism Scale. Data were analyzed using χ² tests, one-way ANOVA, and t-tests. Results: Higher levels of knowledge (conceptual, procedural, and legislative) were associated with more affirmative and non-normative attitudes toward intersex healthcare. Neither gender determinism nor adherence to traditional gender roles was associated with professionals’ attitudes. Participants with prior contact with intersex people demonstrated higher conceptual knowledge and lower support for corrective surgeries. Significant disciplinary differences were also found: physicians tended to display more corrective and ambivalent attitudes, whereas psychologists and social workers were more frequently aligned with affirmative and diversity-respectful perspectives. Conclusions: Intersex healthcare attitudes may be influenced by limited training opportunities and the low visibility of intersex topics in medical education. Knowledge appears to be an important factor associated with more affirmative professional attitudes. Future studies using larger samples are needed to confirm these associations and explore underlying causal mechanisms. Full article

Background: There are differences in lipid metabolism by sex that are relevant for health, but metabolic pathways are not fully understood. We investigated sex differences in cross-sectional associations between metabolic pathways identified using untargeted metabolomics and clinical lipid measures (total cholesterol [TC], triglycerides [TG], and low- and high-density lipoprotein cholesterol [LDL-c; HDL-c]) from blood plasma in the Coronary Artery Risk Development in Young Adults (CARDIA) study (Year 20; 2005–2006). Our objective was to determine whether associations between metabolic pathways and lipid measures differ by sex and to identify pathways that may underlie sex-specific mechanisms of lipid metabolism. Methods: Using data from 2169 participants, (44% women, mean age = 45, 58% White, 42% Black), we used: (1) Orthogonal partial least squares-regression (OPLS-R) to compare variation in TC, TG, LDL-c, and HDL-c explained by metabolites in men vs. women, (2) linear regression to assess sex-modification of associations between 7255 metabolite peaks and lipid measures using false discovery rate (FDR)-corrected p < 0.1, and (3) pathway enrichment analyses to identify metabolic pathways that differed by sex using Fisher’s exact test (FET) p < 0.05. Results: We found that: (1) untargeted metabolomic data reflected variation in lipid measures better for men compared to women, (2) associations between metabolite peaks and lipid measures differed by sex, and (3) 8 unique pathways differed by sex, particularly primary bile acid biosynthesis, linoleic acid metabolism, and arginine biosynthesis. Conclusions: Our findings suggest distinct lipid-associated metabolic activity by sex that points to potential mechanistic pathways. Full article

Background/Objectives: Quasipaa spinosa, a large-sized spiny frog, has high commercial value in the food trade. Although the sexual dimorphism in body size between males and females has been investigated, the sex-determining mechanism in this frog remains unknown. Methods: This study employed a genotyping-by-sequencing (GBS) method to identify sex-associated genomic markers and elucidate the sex determination mechanism in the species. Results: We obtained 853 candidate sex-specific GBS tags, with 811 tags (95.07%) demonstrating a male heterozygous system (XX/XY). The diagnostic specificity of the nine markers was further demonstrated by PCR analysis across multiple adult individuals from seven distinct geographic populations of the frog. Four sex-specific markers were aligned with the DMRT1 gene, representing a master regulator of sex determination and gonadal differentiation across the animal kingdom. Conclusions: Our results deciphered the genetic mechanisms governing sex determination in Q. spinosa and presented effective strategies for mono-sex breeding. Full article

Instant Cascara (IC), a beverage obtained from dried coffee cherry pulp, represents a sustainable hydration option rich in bioactive phytochemicals, such as caffeine, chlorogenic acids, and melanoidins, which may provide effects beyond basic nutrition. This study evaluated the impact of three weeks of IC consumption on somatic and visceral sensitivity, and on neural and immune markers in the colon of male and female healthy Wistar rats. Behavioral tests showed that IC increased locomotor activity and somatic sensitivity in females (p < 0.05). Although control females were more sensitive to visceral pain than males (p < 0.05), IC intake did not significantly alter pain sensitivity in either sex. Histological and immunohistochemical analyses in the colonic myenteric plexus revealed higher enteric glial cell density and glia-to-neuron ratio (p < 0.01), but lower calcitonin gene-related peptide (CGRP)-positive fiber density (p < 0.001) in IC-treated compared to control females. Macrophages decreased in IC-treated compared with control males in the colon wall (p < 0.05), whereas their number increased in IC-treated females compared to IC-treated males (p > 0.0001). Visceral pain responses are associated with complex sex-dependent neuroimmune changes in the colon. Interestingly, IC effects appear mild under healthy conditions, possibly due to compensatory mechanisms exerted by its different phytochemicals. Further investigation is needed to determine the effects of IC in pathological situations involving visceral hypersensitivity, such as brain–gut axis disorders. Full article

Study objective: Electronic vapor product (EVP) use remains prevalent among adolescents in the United States. EVP use may be associated with high-risk substance use behaviors. This study investigates the association between current EVP use and current opioid misuse in high school students. Methods: We conducted a secondary analysis of the 2021 Youth Risk Behavior Survey (YRBS) (n = 7471). We first examined the prevalence rates of current prescription opioid misuse between participants ages 14 to 19 who reported any EVP use compared to those who did not report any EVP use. We conducted an adjusted Poisson regression analysis to determine whether EVP use was associated with prescription opioid misuse after controlling for multiple variables, including age, biological sex, race, ethnicity, alcohol use, other tobacco use, marijuana use, and depressive symptoms. Results: Among participants, 17.2% (95% confidence interval (CI): 15.4–19.1%) reported current EVP use. The prevalence of current opioid misuse was higher in the group of students who use EVPs (13.3%) as compared to students who do not use EVPs (3.2%) (p < 0.0001). Compared to participants who did not use EVPs, those with EVP use had an 80% greater prevalence of opioid misuse, after adjusting in regression analyses (adjusted prevalence rate ratio: 1.8, 95% CI: 1.4–2.3, p < 0.0001). Conclusions: Our findings highlight the significantly increased prevalence of opioid misuse among this population and the need to educate adolescents about the additional risks associated with nicotine and EVP use. Longitudinal studies are needed to test causal relationships and better understand the biobehavioral mechanisms that connect EVP use and opioid misuse. Full article