Despite the widely existence of 2,6-di-tert-butylhydroxytoluene (BHT) and its transformation product 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) in aquatic environments, their chronic ecotoxicological effects remain insufficiently characterized. In this study, zebrafish were exposed to BHT and BHT-Q (0-100 μg/L) from embryo to adult to evaluate potential developmental and reproductive toxicity at environmentally realistic levels. The results revealed that BHT and BHT-Q exposure significantly impaired embryonic development, manifesting as a 17-25% decrease in hatching success, and stunted larval growth. Chronic exposure to BHT and BHT-Q from embryo to adulthood significantly disrupted the hypothalamic-pituitary-gonadal-liver (HPGL) axis-associated organ development and induced a female-biased population ratio in zebrafish. Furthermore, BHT and BHT-Q significantly elevated serum estrogen levels via dysregulation of the HPGL axis, including upregulated transcriptional levels of steroidogenic genes (cyp19a, cyp17, and star) and hepatic vitellogenin (VTG)-encoding genes (vtg1 and vtg3) in female and male, and downregulated transcriptional levels of androgen biosynthesis gene 17βhsd in males. Afterward, F0 zebrafish exposed to BHT and BHT-Q exhibited low production of the fertilized eggs and F1 offspring has slow hatching rate. These findings demonstrate that chronic BHT and BHT-Q exposure disrupts endocrine function and reproductive fitness in zebrafish, highlighting their potential ecological risks at environmentally relevant levels.
Virtual Reality (VR) has been proposed as a tool in rehabilitation to create more realistic, interactive, and engaging environments that can enhance the sense of embodiment, and thus possibly the effect of the treatment itself. Previous research has shown that combining movement observation with somatosensory stimulation may further improve training outcomes. The present study aimed to examine whether a protocol integrating the observation of human movements within an VR environment with proprioceptive stimulation, thereby establishing a Proprioceptive-Augmented virtual Reality (PAR) paradigm, could enhance participants' ability to imitate the dynamic properties of movements presented in VR. Twenty-three healthy young adults were asked to imitate the features of a flexion-extension forearm movement observed in an immersive VR environment, either while receiving or not receiving 80 Hz muscle tendon vibration that induced an illusory sensation of movement congruent with the observed direction (PAR). The imitation task was performed with the stimulated forearm either after the stimulation had ended (OFFLINE imitation) or concurrently with it (ONLINE imitation). Participants' ability to reproduce the avatar's mean and maximal velocities was assessed (reproduction error). Root means square error (RMSE) between avatar and participants' trajectory was calculated. In addition, a questionnaire evaluating the sense of embodiment was administered after the OFFLINE imitation task under both conditions, as well as the evaluation of the vividness evoked by PAR and VR. In the OFFLINE task the reproduction error was lower in PAR than in VR, while the opposite was obtained in the ONLINE task. In the OFFLINE task no difference emerged between PAR and VR RMSE values, whilst in the ONLINE task PAR RMSE was higher than that in VR. PAR evoked a higher sense of embodiment and higher vividness compared to VR when considering all the domain tested (body ownership, sense of agency, location of the body). These findings indicate that proprioceptive stimulation in the PAR condition positively affected movement reproduction during the OFFLINE imitation task, likely benefiting from the heightened sense of embodiment and vividness elicited in this condition. This suggests that muscle tendon vibration can enhance the perception of self-motion in VR, enabling richer interaction strategies and offering promising prospects for sensorimotor rehabilitation.
The evolution of seeds was a critical transition in plant evolution, but how ancestral seedless development was modified to form the first seed is only partly-answered through comparative morphology or the fossil record. We investigate seed origins by quantifying gene network conservation between seeds and seedless plant reproductive organs. Characterizing reproduction in the homosporous fern Ceratopteris richardii as a proxy for ancestral seedless reproduction, we create a gene expression atlas of fern diploid and haploid reproductive organ development and test for enrichment of these genes in Arabidopsis thaliana. Here we show ovule gene networks are enriched in genes regulating post-fertilization development of the fern haploid egg chamber (archegonium), a subset of which also show enrichment in sporophyll primordia, suggesting a mechanistic model to explain the origin of the ovule from a sporangium-bearing axis whereby gene networks in the ancestral post-fertilization archegonium became heterotopically expressed during development of the sporangium-bearing axis.
This paper investigates the dynamical behavior of a class of stochastic tumor-immune interaction systems incorporating Ornstein-Uhlenbeck (OU) processes. We first establish a four-dimensional deterministic ordinary differential equation (ODE) model describing the interactions among tumor cells, natural killer (NK) cells, CD8+T cells, and dendritic cells, then extend this model by incorporating OU processes to account for intrinsic stochastic perturbations with memory effects in the tumor microenvironment. Subsequently, the existence and local stability of equilibrium points in the deterministic system were analyzed, identifying multiple steady states, including death equilibrium, tumor-free equilibrium, and tumor-present equilibrium, along with their stability conditions. Further, the existence and uniqueness of global solutions for the stochastic system were proven, and an existence theorem for steady distributions was established using the Lyapunov function method. Moreover, through decoupling time scales, the system was simplified into a coupled model of tumor cells and OU noise. The stochastic basic reproduction number R0s was defined, revealing the system's threshold behavior: when R0s<1, tumors almost certainly become extinct; when R0s>1, tumors persist with positive probability. The study also identifies a critical noise intensity σc. When σ > σc, the system may undergo a noise-induced phase transition from extinction to persistence, even if the deterministic reproduction number R0<1. This research provides theoretical foundations for understanding the nonlinear dynamics of tumor-immune systems and may provide ideas for the future development of immunotherapies.
Most existing studies on disease transmission models concentrate on identifying control measures required to reduce the reproduction number below unity, with a primary focus on epidemic dynamics preceding the infection peak. However, the cumulative numbers of infections and deaths occurring after the epidemic becomes controllable (that is, the effective reproduction number drops to one) remain critical yet insufficiently explored. In this study, we systematically investigate post-peak epidemic indices by deriving explicit analytical results for the cumulative numbers of infected and deceased individuals following the infection peak within the SIR (Susceptible-Infected-Recovered) model framework. We present closed-form expressions for the epidemic peak and its timing, and rigorously establish sharp upper bounds for cumulative infections and deaths after the peak. The theoretical results are validated through numerical simulations based on three representative real-world epidemic scenarios. These findings advance the theoretical understanding of epidemic dynamics in SIR models with diverse incidence rates and offer practical tools for accurately assessing post-peak risks, thereby informing more effective public health interventions and resource planning. We finally explore, within some extended general model frameworks, the characteristics of cumulative numbers of infected and deceased individuals following the infection peak, and discuss the intrinsic limitations that prevent exact analytical expressions and upper bounds.
At present, there have been many studies on the effects of heavy metals on plants and microorganisms, but there is a lack of relevant studies on long-term effects. The purpose of this study was to systematically clarify the spatiotemporal distribution of heavy metals in soil-plant system and the responses of soil bacterial communities adjacent to a tailing dam piling up over 50 years. Soil pH, total organic carbon (TOC), particle size, soil bulk density (BD), and heavy metals (V, Cr, Cd) and Heteropogon contortus, were selected and analyzed on the MaJiaTian (MJT) tailing dam along the phytoremediation chronosequence. Our results demonstrated that the enrichment of heavy metals in soil were caused by long-term tailing dumping. The concentration of Cd and the extractable fraction of heavy metals in the roots have been increased with reclamation time, which markedly affected the compositions of bacterial communities in rhizosphere soils. Furthermore, the abundance of Proteobacteria (from 16.8% to 26.0%) and Patescibacteria (from 2.00% to 4.00%) in surface soil has also gradually increased with time. It's observed that the Heteropogon contortus rhizosphere activated the soil microbial communities. Soil acid-soluble fraction of vanadium (Acid-V) was found to affect bacterial community abundance negatively (λ = -0.529, p < 0.001). The majority of networks topological properties differ significantly according to null distribution models, confirming that rhizosphere effects non-randomly alter co-occurrence patterns. This study reveals Heteropogon contortus and corresponding rhizosphere bacterial communities can improve soil microecology through their growth and reproduction along 50 years.
Due to recent advances in green energy initiatives in response to climate change impacts, lithium exploration and production are rapidly increasing, with concomitant elevated lithium in discharges to waterways. However, lithium toxicity to aquatic species is not well understood, particularly in relation to sublethal effects. As such, lithium has become an element of interest for environmental regulators, particularly in Western Australia, currently the largest producer of lithium globally. This study provides the first published assessment of lithium toxicity using locally-relevant freshwater species from southwest Australia-a Global Biodiversity Hotspot and location of the world's largest lithium mine. Here, chronic toxicity of lithium was assessed using a novel suite of eight temperate southwest Australian aquatic-species tests undertaken in moderately hard water reflective of the region. Sensitivity to lithium based on no (significant) effect concentration (N(S)EC), from most to least sensitive was: cladoceran, Ceriodaphnia dubia > cladoceran, Simocephalus exspinosus > green alga, Chlamydomonas oviformis, > green alga, Scenedesmus sp. > green alga, Tetradesmus obliquus > hydroid, Hydra viridissima > green alga, Chlorella sp. > pulmonate snail, Glyptophysa georgiana. Environmentally relevant concentrations resulted in toxicity in all species. Reproduction was affected in snail and cladoceran species, while population growth and cell yield were inhibited in hydroid and algal species respectively. Both N(S)ECs and median effect concentrations (EC50s) ranged from 862-2,830 µg/L and 1,120-5,760 µg/L respectively (<0.45 µm filtered). Southwest Australian species were in some cases more sensitive to lithium than their international and interstate counterparts, highlighting the necessity for appropriate species test selection for this bioregion. This dataset is available to inform environmental risk assessment and future aquatic guideline value derivation through species-sensitivity-distributions.
Perceived discrimination can undermine healthcare system trust and contribute to medical mistrust, creating barriers to effective survivorship care. Endometrial cancer survivors, who experience intersecting social, reproductive, and aging-related challenges, remain understudied, and population-level evidence on the relationship between discrimination and medical mistrust in this group is limited. We analyzed enrollment survey data from the population-based Carolina Endometrial Cancer Study. Perceived discrimination was measured using the 9-item Everyday Discrimination Scale, categorized into tertiles (low, moderate, high). Medical mistrust was assessed using the 7-item Medical Mistrust Index (MMI), dichotomized as ≥ 1 item endorsed. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), adjusting for age at diagnosis, region, education, and caregiving support. Analyses were conducted overall and stratified by race, education, and geography, with sensitivity analyses of frequency- and chronicity-based discrimination measures. Among 907 survivors (35% Black, mean age 60.9 years), nearly half reported moderate or high perceived discrimination, and more than 80% endorsed ≥ 1 MMI item. Compared with low discrimination, moderate (aPR = 1.20, 95% CI: 1.12-1.30) and high discrimination (aPR = 1.26, 95% CI: 1.17-1.34) were associated with a higher prevalence of mistrust. Associations were consistent across racial, educational, and geographic subgroups. Sensitivity analyses confirmed that both the frequency and intensity of discrimination were positively associated with mistrust. Perceived discrimination was common and strongly associated with mistrust among endometrial cancer survivors. Our findings highlight the need for culturally responsive survivorship care and equity-focused interventions to strengthen trust and engagement.
The Latin American and Caribbean region (LAC) has historically been an early adopter of new vaccines, including the recently introduced maternal vaccine to protect infants against respiratory syncytial virus (RSV). Since maternal RSV vaccination requires gestational age (GA)-specific administration, antenatal care (ANC)-based delivery feasibility depends on ANC visit timing and frequency. We assessed ANC attendance relative to recommended vaccination windows in four LAC countries to inform planning for maternal RSV vaccine implementation and future maternal immunization programs. We conducted a retrospective, cross-sectional analysis from Perinatal Information System data across eight tertiary facilities in Bolivia, Ecuador, Honduras, and Uruguay. Women 15-45 years old with ≥1 ANC visit in 2023 and a live, singleton birth at a study facility were included. GA per visit was extracted or derived from last menstrual period or birth data. We defined RSV vaccination eligibility according to Pan American Health Organization (PAHO) (32-36 weeks) and World Health Organization (WHO) (≥ 28 weeks) recommendations. Descriptive analyses summarized ANC initiation, visit timing, and the proportion of women attending visits within eligibility windows. We included 37,604 women. The median GA at ANC initiation was 12 weeks, ranging from 10 weeks (Uruguay) to 15 weeks (Ecuador). Overall, 63.5% of women attended at least one ANC visit during the PAHO window, with country-specific proportions from 53.6% (Honduras) to 82.3% (Uruguay). Attendance within the WHO window was higher (91.4%). Median ANC attendance was five visits, ranging from five (Honduras) to eight (Uruguay). Earlier ANC initiation was associated with higher visit counts. There is substantial potential for achieving high maternal RSV vaccine coverage in LAC, particularly per broader WHO vaccine recommendations. Where ANC begins later or visits are fewer, narrower vaccine-eligible windows may limit achievable coverage. Strengthening early ANC engagement and immunization counseling may increase vaccination opportunities.
The postmenopausal bone health reflects the influence of various factors that have been in effect throughout life and hormonal regulation is among them. The aim of the current study is to investigate the effect of pregnancies and other factors related to female reproductive health on bone mineral density and the incidence of fractures in the postmenopausal period. We performed a case-control retrospective analysis in a group of 977 postmenopausal women from the RACOST-POL cohort. In the study group, there were 894 (91.5%) women who had at least one delivery and breastfeeding was reported by 845 (86.5%) women. Bone mineral density (FN T-score) was not related to pregnancies and history of lactation, but correlated positively with age at menopause and with time of reproductive period. Low-energy fractures were reported by 286 women, which consists 29.3% of the study group. There was no difference in fracture prevalence between women who delivered (29.4%) or not (27.7%). Also the breastfeeding status was not related to fracture prevalence (28.9% in the subgroup declaring lactation and 31.8% in the others). Women with fractures had earlier age of menopause and shorter time of reproductive period in comparison to subjects without fractures (48.3 ± 5.2 vs. 49.5 ± 4.7 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), and 34.1 ± 5.5 vs. 35.5 ± 4.9 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), respectively). Additionally, fracture prevalence in the 'early menopause' (below 45 ys) subgroup was significantly higher (39.1%) than in all the others (27.8%) with OR 1.66 (95% CI: 1.13 - 2.42). Our study did not show a significant association between history of pregnancies or lactation and the skeletal status in the postmenopausal period. However, a shortened period between menarche and menopause and an earlier age at menopause may have a negative impact on bone health in later life. Presented results complement the knowledge on a wide and diverse spectrum of factors modifying bone health in postmenopausal women.
The revised FIGO 2023 for endometrial cancer (EC) incorporates lymphovascular space invasion (LVSI) into staging and explicitly designates only substantial/extensive LVSI as adverse. While reduced field-of-view diffusion-weighted imaging (rFOV DWI) improves image quality and staging accuracy for EC, its potential for radiomics-based LVSI assessment remains underexplored. We compared radiomics models based on rFOV DWI and conventional DWI (cDWI) for preoperative prediction of substantial/extensive LVSI and assessed external generalizability. We included 206 patients: 130 from Hospital A (training/internal test) and 76 from Hospital B (external rFOV DWI test). Whole-tumor radiomics features were extracted from T2WI, rFOV DWI/ADC, and-at Hospital A only-cDWI/ADC. Two calibrated gradient-boosted tree classifiers were developed: rFOV DWI and cDWI models. Discrimination was summarized by AUC with 95 % CIs from stratified bootstrap; generalizability was evaluated in the test sets. On the internal test set, the rFOV DWI model achieved an AUC of 0.90 (95 % CI, 0.77-1.00) with sensitivity 1.00, specificity 0.77, and balanced accuracy 0.89; the cDWI model showed an AUC of 0.89 (95 % CI, 0.72-1.00) with sensitivity 0.75, specificity 0.68, and balanced accuracy 0.72. On the external test set, the rFOV DWI model yielded an AUC of 0.74 (95 % CI, 0.56-0.90). Feature importance favored diffusion-related textures; in both models, DWI/ADC features outweighed T2WI. The rFOV DWI-based model achieved higher sensitivity without a significant AUC advantage over cDWI. External testing showed a decline in performance despite harmonization. Multicenter validation is required before clinical implementation.
This trial evaluated the combined effect of yoga and camelina sativa powder (CSP) on glycemic indices, inflammatory and oxidative stress parameters in women with type 2 diabetes mellitus (T2DM). In this trial, 80 patients with T2DM were randomly allocated into four groups: group 1 (placebo), group 2 (receiving CSP), group 3 (doing yoga), and group 4 (receiving CSP and doing yoga) for 8 weeks. Glycemic indices, inflammatory and oxidative stress parameters were assessed pre-and post-intervention. CSP plus yoga treatment significantly increased the McAuley-index and Quick-index compared to the placebo group (P = 0.021 and P < 0.001, respectively). A significant decrease in the glycemic exposure (GE) index (P = 0.010), fasting blood sugar (FBS) (P = 0.003), hemoglobin A1c (P = 0.013), insulin (P = 0.002), and homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001) was found in the CSP plus yoga group compared to the placebo after adjustment for confounders. Serum superoxide dismutase level significantly increased in camelina, yoga, and both CSP plus yoga groups compared to the placebo group (P < 0.001, P = 0.019, and P = 0.005, respectively). Serum catalase levels increased significantly in CSP plus yoga group compared to the placebo following 8 weeks (P = 0.022). Malondialdehyde concentration declined significantly in yoga and CSP plus yoga groups compared to placebo (P = 0.017 and P < 0.001, respectively). Serum tumor necrosis factor-α (TNF-α) level significantly decreased in CSP, yoga, and combined CSP plus yoga groups compared with the placebo group (P < 0.001, P = 0.033, and P < 0.001, respectively). We found a favorable effect of co-treatment of CSP and yoga for 8 weeks in women with T2DM on some glycemic indices, oxidative stress, and inflammatory parameters. The combined effect of yoga and camelina sativa powder on glycemic indices, inflammation, and oxidative stress. PPAR-γ: peroxisome proliferator-activated receptor gamma, NF-kB: nuclear factor kappa B, GLP: glucagon-like peptide, PYY: peptide YY, SCFA: short chain fatty acids, ROS: reactive oxygen species, LPS: lipopolysaccharides, HPA: hypothalamic-pituitary-adrenal axis.
In assisted reproductive technology (ART), in vitro maturation (IVM) is critical for advancing oocytes from the first meiosis to the second meiotic metaphase II (MII) stage, a prerequisite for successful embryo development. However, oocytes are particularly vulnerable to oxidative stress during in vitro production and maturation. Isoorientin (ISO), a natural flavonoid, has demonstrated a range of physiological and pharmacological properties, including antioxidant, anti-inflammatory, anxiolytic, anti-myocardial ischemia, and lipid metabolism regulation effects. In our studies, treatment with ISO at optimal concentrations during the IVM phase significantly enhanced oocyte maturation rates and subsequent embryo development. This was accompanied by reduced reactive oxygen species (ROS) levels, increased mitochondrial membrane potential, elevated ATP content, and enhanced lipid droplet and fatty acid accumulation. Additionally, upregulation of β-oxidation-related genes was observed. Notably, ISO treatment also reduced iron accumulation via SIRT1-associated pathways, mitigated endoplasmic reticulum stress caused by lipid peroxidation, and reversed iron-induced cell death in oocytes.
β-Thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the β-globin chain, leading to variable clinical severity and substantial lifelong health burden. Because prevention depends heavily on awareness, screening, and informed reproductive decision-making, understanding public knowledge, attitudes, and practices is essential for designing effective control strategies. An analytical cross-sectional study was conducted between November 2025 and January 2026 using a structured, self-administered Arabic questionnaire distributed online through Google Forms. The survey was adapted from a previously validated thalassemia KAP instrument and disseminated using snowball sampling through social media platforms. The minimum required sample size was 358, calculated using a single-proportion formula with an expected awareness proportion of 36.8% from a previous young-adult β-thalassemia KAP study, 95% confidence level, and 5% margin of error. A total of 424 Palestinian participants were included in the final analysis. Participants who had never heard of thalassemia were classified as unaware and excluded from domain-based KAP scoring analyses. Knowledge, attitude, and practice domains were scored using Bloom's 60% cut-off criterion. Descriptive statistics, chi-square tests, t-tests, ANOVA, correlation analyses, and multivariable logistic regression were used for data analysis. Overall, 87.0% of participants had heard of thalassemia. Among aware participants (n = 369), 46.1% demonstrated adequate knowledge, 73.7% had a positive attitude, and 82.7% had positive practice. Knowledge was stronger for hereditary concepts, carrier status, and the role of consanguinity, but weaker for disease treatability, clinical subtypes, and prevention policies. Females had significantly higher knowledge and practice scores than males, while positive attitude did not differ significantly by sex. Previous screening uptake was limited, but endorsement of premarital testing, prenatal diagnosis, and knowledge sharing was high. Knowledge score was positively correlated with practice score and independently predicted positive practice (aOR = 1.35, 95% CI: 1.15-1.57, p < 0.001). Female sex, increasing age, and higher education were independently associated with adequate knowledge. Although awareness of beta thalassemia among Palestinian young adults was high, important gaps remained in functionally relevant knowledge and in the translation of preventive intentions into actual screening behavior. The independent association between knowledge and positive practice suggests that strengthening practical genetic literacy may be a key pathway for improving prevention-oriented behavior. These findings support the need for culturally appropriate educational strategies, premarital counseling, and community-based initiatives to enhance informed decision-making and strengthen thalassemia prevention efforts in Palestine. Nurse-led health education, premarital counseling, and accessible community-based screening may help translate awareness into informed preventive action.
Artificial intelligence (AI)-powered large language models (LLMs) are increasingly used as adjunctive tools in education, research, and patient care. This systematic review aimed to investigate the current literature on the applications, performance, and ethical considerations regarding the use of artificial intelligence (AI), including large language models (LLM) in plastic and reconstructive surgery. A comprehensive search of PubMed, Scopus, and Cochrane Library was conducted by two independent investigators for studies published in English in peer-reviewed journals reporting findings about applications (education, clinical decision-making, research process), ethical and practical challenges (bias, data privacy, and accountability), and performance of LLMs in facial plastic and reconstructive surgery practice. PRISMA statements and PICOTS frameworks were used for conducting the search and summarizing the literature findings. Twenty-one studies met inclusion criteria, including 11 examining practical uses of ChatGPT and other LLMs, 8 evaluating performance on medical and surgical tasks, and 7 assessing ethical issues and potential limitations. Based on several performance tools, LLMs demonstrated moderate-to-high accuracy, ranging from 54.96% to 77.3%, for generating operative notes, improving patient communication, and conducting literature synthesis. The following concerns were identified in the literature: risk of hallucination or misinformation, lack of data protection compliance, and insufficient transparency. More robust evidence-based longitudinal investigations are needed to establish not only safety and effectiveness but also real-world feasibility. LLMs report promising application results in plastic and reconstructive surgery, particularly for educational and administrative purposes. The use of LLMs in plastic and reconstructive surgical practice remains limited by the lack of evidence-based longitudinal investigations and unclear data protection and ethical frameworks.
Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) leads to significant economic losses for the global swine industry. Screening and identification of PRRSV-regulated host proteins, followed by the development of long-acting anti-PRRSV therapeutics targeting these genetically stable host factors, represents a mainstream research direction in this field. Glucose-6-phosphate transporter (G6PT) is a core regulator of glucose uptake. However, its role in PRRSV infection remains unknown. Here, we report for the first time that PRRSV infection significantly upregulated the expression of G6PT in MARC-145 cells, a monkey kidney cell line, and in porcine alveolar macrophage (PAM)-Tang, a PAM-derived immortalized cell line. Functionally, overexpression of G6PT facilitated PRRSV replication, while knockdown of G6PT inhibited PRRSV replication. These findings indicated that G6PT contributed to efficient PRRSV propagation. Mechanistically, G6PT suppressed retinoic acid-inducible gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated type I interferon transcription in a manner independent of its canonical G6P transport activity. Furthermore, G6PT overexpression upregulated key glycolytic enzymes, including hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). In conclusion, we propose that PRRSV hijacks G6PT to promote its replication by suppressing innate immunity and enhancing aerobic glycolysis, identifying G6PT as a potential novel target for anti-PRRSV drug development.
Ovarian endometriosis is an estrogen-dependent inflammatory disorder in which endometrial stromal cells are key cellular contributors to hormone-immune crosstalk and lesion persistence. Here, we isolated paired eutopic (NESC) and ectopic (EESC) endometrial stromal cells from patients with ovarian endometriosis, compared their proliferation, migration/invasion and decidual responsiveness, and profiled their transcriptomes by RNA sequencing. EESCs displayed enhanced proliferative and migratory/invasive capacity and an attenuated decidual response. RNA-seq revealed an inflammatory transcriptional program with enrichment of cytokine-cytokine receptor interaction and MAPK-related pathways and increased expression of chemokines and pro-inflammatory cytokines. Steroid receptor analyses showed reduced ERα and progesterone receptor expression with relative ERβ predominance, consistent with progesterone-resistance-like features. We then generated SV40 large T antigen-immortalized NESC and EESC lines. These lines showed stable growth and retained stromal identity and several disease-relevant phenotypic features, while also acquiring immortalization-associated transcriptomic remodeling involving cell-cycle, DNA-replication and proliferation-related programs. These paired primary and immortalized stromal cell models provide a practical platform to investigate endocrine-immune mechanisms in endometriosis and to facilitate preclinical screening of therapies targeting inflammatory and steroid signaling.
The widespread presence of neonicotinoid insecticides (NNIs) in aquatic environments raises significant ecological concerns. This review aims to summarize the toxicological effects and mechanisms of representative NNIs and their mixtures on zebrafish (Danio rerio). Current evidence reveals that individual NNIs induce multidimensional adverse outcomes across various physiological systems, primarily causing neurotoxicity, endocrine disruption, and developmental impairment. Furthermore, in realistic environments, NNI mixture toxicity depends on chemical composition and ratios. These mixtures display either synergistic or antagonistic effects. Under specific ratios, synergistic combinations worsen neurodevelopmental and reproductive damage. In conclusion, both individual and mixed NNIs pose severe health hazards to aquatic organisms. To accurately reflect natural aquatic conditions and protect aquatic ecosystems, future environmental risk assessments must prioritize the joint toxicity of pesticide mixtures.
To evaluate whether progesterone-induced changes in endometrial thickness (EMT) affect singleton infant outcomes during frozen-thawed embryo transfer (FET) cycles. This retrospective study analyzed 6,331 singleton live births following frozen-thawed Day 3 embryo transfers. EMT was measured via transvaginal ultrasound one day before progesterone initiation and on the day of FET. Participants were grouped by EMT change: increase, decrease, or stable. Primary outcomes included mean birthweight, low birthweight (LBW), and small-for-gestational-age (SGA) status. Associations between EMT changes and neonatal outcomes were evaluated using multivariable linear and logistic regression. No significant differences in mean birthweight were observed among the three groups (3,355.30 ± 502.69 g vs. 3,351.30 ± 474.79 g vs. 3,344.26 ± 514.54 g; p = 0.753). Compared with the EMT stable group, the EMT decreased group showed no significant increase in LBW (1.1%; aOR 1.645, 95% CI 0.818-3.307) or SGA (2.7%; aOR 1.141, 95% CI 0.783-1.662). Similarly, the EMT increased group showed no significant association with LBW (aOR 1.310, 95% CI 0.723-2.375) or SGA (aOR 0.912, 95% CI 0.660-1.261). Multiple linear regression confirmed that gestational age and infant gender significantly influenced birthweight, while EMT change did not. EMT may increase, decrease, or remain stable after progesterone administration in FET cycles. However, these changes do not demonstrate an independent association with adverse perinatal outcomes in term singleton infants.
D-ribose-L-cysteine (DRc) has been shown to protect against copper-induced neurotoxicity. However, its potential protective effect against copper-induced testicular toxicity has not been previously investigated. The present study aimed to evaluate the protective efficacy of DRc against copper-induced gonadotoxicity and to elucidate the underlying mechanisms using complementary in vivo and in silico approaches. Male Swiss mice were administered oral treatments of copper sulfate [CuSO4 (100 mg/kg)] and/or DRc (10, 25, and 50 mg/kg) once a day for 28 days. After euthanization, the epididymal sperm were immediately subjected to semen analysis, and the excised testicular tissues were processed for biochemical and histomorphological assays. In parallel, network pharmacology analysis was performed to predict key molecular targets and pathways associated with DRc-mediated gonadoprotection. DRc significantly improved copper-induced reproductive toxicity, as evidenced by improvements in sperm count, motility, viability, morphology, gonadosomatic index, testosterone levels, and testicular histoarchitecture. These protective effects were accompanied by a marked reduction in oxidative stress (decreased levels of MDA and NO, and increased levels of GSH and SOD), inflammation (e.g., decreased IL-6 and TNF-α), and apoptosis (e.g., decreased caspase-3). Network pharmacology analysis identified 19 targets, including caspase-3 (CasP3), X-linked inhibitor of apoptosis protein (XIAP), nitric oxide synthase 1 (NOS1), Janus kinase 2 (JAK2), and DNA repair protein (RAD50), suggesting coordinated regulation of oxidative stress, inflammatory, apoptotic, and DNA repair pathways. Taken together, DRc mitigates copper-induced gonadotoxicity through modulation of oxidative-inflammatory, apoptotic, and DNA repair machinery.