Nanoplastics (NPs) are emerging as significant environmental hazards, especially in aquatic ecosystems, where they predominantly exist in aged forms due to weathering processes. Fish, known for their remarkable ability to regenerate injured caudal fins through intricate biological mechanisms, serve as an ideal model for studying sublethal effects of environmental pollutants. This study investigates the toxic impacts of aged polystyrene nanoplastics (PS-NPs) on caudal fin regeneration in goldfish, focusing on molecular, cellular, and physiological responses. Goldfish were exposed to UV-aged PS-NPs (50 nm) at concentrations of 0, 10, 100, and 1000 μg/L, and regeneration was monitored at 7-, 14-, and 35 days post-amputation (dpa). Results demonstrated that caudal fin regeneration was significantly impaired in a concentration- and time-dependent manner. Under exposure to a low concentration (10 μg/L) of aged PS-NPs, goldfish showed an adaptive antioxidant response. Exposure to medium-high concentrations (100-1000 μg/L) led to abnormal ROS activity, disordered apoptosis, and abnormal transcription of core genes in oxidative stress (gpx, sod), immune-inflammation (mpeg1, il-1β, tnf-α), and regeneration pathways (fgf20a, runx2a). This ultimately led to a significant inhibition of caudal fin regeneration at 35 dpa. This study indicates that UV-aged PS-NPs can inhibit the regeneration of goldfish tail fins by disrupting the coordinated function of the oxidative stress-immune-apoptosis-regeneration pathway. The study highlights the risks posed by aged NPs in aquatic environments, emphasizing their potential to impair critical tissue regeneration processes in fish, with broader implications for ecosystem health and resilience.

Fluoride (F-) exerts a dual role in agricultural systems, supporting dental mineralization at low levels but inducing multiorgan toxicity under chronic exposure. While the detrimental effects of F- have been well documented, its interactions with co-occurring micronutrients (e.g., Zn, Se, I) and toxicants (e.g., Al, Cd, As) remain incompletely characterized in the context of food production and animal husbandry. Accumulating evidence indicates that essential micronutrients can attenuate F- toxicity by potentiating antioxidant defenses and stabilizing metalloenzyme activity, whereas toxicants aggravate F--mediated injury through synergistic oxidative damage. These multielement interactions modulate F- bioavailability, tissue distribution, and organ-specific pathology in livestock tissues and food commodities. Critical knowledge gaps persist regarding cumulative exposure thresholds and the practical relevance of animal models for food safety risk assessment. This review synthesizes mechanistic insights into F--element interactions and discusses emerging mitigation strategies to prevent or ameliorate fluorosis under real-world multicontaminant scenarios in agricultural settings.

Fluoride, a common agricultural additive used to enhance plant resilience and pest control, poses toxicity risks when exposure surpasses safe thresholds, affecting ecosystems and human health. While its reproductive toxicity is recognized, the sex-specific and cross-generational effects remain underexplored. To address this gap, we employed an integrative approach combining transcriptomics (next-generation sequencing (NGS)), bioinformatic network analysis, gut microbiota sequencing, and in vivo functional assays. ICR mice (F0 generation), both male and female, were exposed to fluoride (100 mg/L in drinking water) for 35 days, continuing through gestation and offspring weaning. Our transcriptomic analysis revealed significant upregulation of autophagy (via the PI3K-AKT-mTOR pathway) and oxidative stress-induced mitochondrial dysfunction in gonadal tissue, with more pronounced effects observed in males. Further integrated analyses of transcriptomic and metabolomic data, supported by in vivo experiments, highlighted oxidative stress, mitochondrial dysfunction, and PI3K-AKT-mTOR pathway activation with stronger effects in males. The principal component analysis confirmed sex-specific transcriptome alterations, with males showing more substantial disruption. Additionally, 16S rRNA sequencing identified significant gut dysbiosis, particularly in males, with an increased Firmicutes/Bacteroidetes ratio and higher abundances of Oscillospirales and Anaerovoracaceae. Moreover, our study identified significant correlations between specific gut microbiota (e.g., Firmicutes, Proteobacteria) and autophagy, oxidative stress, and mitochondrial dysfunction pathways, with notable sex-dependent differences. These findings suggest that gut microbiota may play a critical role in modulating fluoride-induced reproductive toxicity, particularly through their effects on oxidative stress and cellular homeostasis. The breakdown of the gut barrier and elevated serum/gonadal lipopolysaccharide (LPS) levels in fluoride-treated mice further established a link between gut dysbiosis and fluoride-induced reproductive toxicity. These findings underscore the importance of considering sex differences in xenobiotic-induced reproductive and developmental toxicity.

Eimeria tenella (E. tenella) causes severe coccidiosis in chickens, leading to bloody diarrhea, growth retardation, high mortality, and substantial economic losses. Rising drug resistance and residue concerns limit conventional chemical anticoccidials, driving interest in Traditional Chinese Medicine as a safe, cost-effective, and sustainable alternative. To investigate the effects of Sophora flavescens seed extract (SFSE) on E. tenella-infected chicken ceca, 12-day-old chickens were assigned to control, infection, and SFSE groups, with the latter two orally inoculated with sporulated E. tenella oocysts on day 14. Samples were collected at 5- and 7-days post-infection (DPI). Cecal histopathology was assessed with HE and Masson’s trichrome staining. DNA damage was detected by TUNEL assay. Goblet cell distribution and glycoprotein composition were evaluated using PAS and AB-PAS staining, respectively. Apoptosis-related proteins, mucins, and cell junction proteins were analyzed via immunofluorescence. Myosin light chain kinase (MLCK) expression was examined via immunohistochemistry analysis. Parameters including relative weight gain, survival rate, oocyst value, cecal lesion score, and anticoccidial index (ACI) were assessed. SFSE treatment improved growth performance, alleviated cecal tissue damage and fibrosis, and yielded an ACI value of 126.26. SFSE reduced Caspase-3 expression and elevated the Bcl-2/Bax ratio. Furthermore, SFSE enhanced intestinal mucosal barrier function by increasing goblet cell counts, glycoprotein expression, and MUC2 and TFF3 secretion. The expression of tight junction proteins Occludin, ZO-1, E-cadherin, and Desmoplakin was upregulated, whereas Claudin-2 and MLCK were downregulated. Collectively, SFSE treatment showed partial anticoccidial efficacy by alleviating cecal damage and apoptosis, increasing goblet cell numbers and mucin secretion, and downregulating MLCK to restore tight junction proteins, thereby improving intestinal barrier function. This study provides a scientific basis for using traditional Chinese medicine in preventing and treating avian coccidiosis, with significant clinical relevance.

Eimeria tenella (E. tenella), an obligate intracellular apicomplexan parasite, invades chicken cecal epithelial cells, causing severe chicken coccidiosis. During the host invasion process, actin provides the driving force for E. tenella. Actin depolymerization factor (ADF), an actin binding protein, can regulate actin filaments turnover and cytoskeleton reconstruction, playing a critical role in parasite gliding invasion of host cells. Diclazuril, a benzeneacetonitrile anticoccidial agent, exhibits potent activity against E. tenella. However, mechanism of diclazuril action on ADF against E. tenella remains unclear. In this study, a chicken model infected with E. tenella was established, and the second-generation merozoites were subsequently harvested from both infected and diclazuril-treated groups. EtADF subcellular localization was assessed by immunofluorescence, while total and phosphorylated EtADF (p-EtADF) expression levels were quantified via western blotting. Subsequently, the in vitro depolymerization and polymerization kinetics of actin were monitored using a fluorescence spectrophotometer. Actin co-sedimentation assay and SDS-PAGE were employed to assess the biological activity of EtADF, while the F-actin morphology was examined using transmission electron microscopy (TEM). Results demonstrated that EtADF was localized in cytoplasm of E. tenella second-generation merozoites, and diclazuril reduced total EtADF expression while increasing p-EtADF levels. Actin dynamics assays, co-sedimentation analysis, and TEM revealed that EtADF exhibits F-actin binding, bundling and depolymerization activities, as well as G-actin sequestering and polymerization inhibition. Diclazuril effectively inhibited these activities of EtADF. Collectively, these findings provide important insights into molecular mechanism underlying the anticoccidial effect of diclazuril, and highlight EtADF as a potential novel drug target.

Osteoporosis is a metabolic bone disease primarily caused by a decreased bone formation and increased bone resorption. Osteoclasts are a special class of terminally differentiated cells that play an important role in normal bone remodeling and bone loss in osteoporosis as well as in a variety of osteolytic diseases. Osteoclasts can be differentiated from monocyte-macrophage cells of the hematopoietic system; they are the key cells in bone resorption. Osteoclast formation and differentiation are regulated by various cytokines and transcription factors. In this review, we summarize recent advances in research on the regulation of osteoclast differentiation and function by factors such as M-CSF, RANKL, AP-1, NFATC1, MITF, and PU.1. Understanding these cytokines and transcription factors can not only help identify targets for osteoclast differentiation but also aid in intervening in the treatment of osteoclast-related diseases.

Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice. To explore these mechanisms, F0 pregnant mice were exposed to deionized water (control) or 100 mg/L sodium fluoride (NaF) during gestation and throughout the F1 generation (n = 16 females/group), covering puberty to weaning and maturity. NaF exposure caused significant reductions in body weight, organ coefficients, and pathological indices, with increased ovarian autophagic vacuoles, mitochondrial injuries, and elevated serum/ovary LPS levels in F1 females. qRT-PCR, fluorescent staining, biochemical assays, and Western blotting confirmed the activation of IL-17 signaling, apoptosis, and autophagy. Moreover, 16S rRNA sequencing revealed gut microbiota dysbiosis in NaF-exposed F1 females, potentially exacerbating ovary injury via serum LPS elevation. The gut dysbiosis could justify deteriorated serum LPS levels and its connection to F-induced ovary injury. These findings provide mechanistic insights into fluoride-induced reprotoxicity, emphasizing the interplay of IL-17 signaling, autophagy, and apoptosis in disrupting cellular homeostasis and suggesting potential therapeutic targets.

Decabromodiphenyl ethane (DBDPE) is one of the most extensively used novel brominated flame retardants, and it has been frequently detected in the global environment. Although organisms encounter various pollutants through the intestine, the toxicity effects of DBDPE exposure on the intestine and the potential mechanisms remain unclear. Here, by morphological observation, histopathology, high-throughput sequencing, and transcriptomics methods, we evaluated the effects of environmental (0.011 and 0.11 mu g/g dw) and extreme DBDPE concentrations (1.1 and 11 mu g/g dw) on the intestine of silkworms. Morphological observations revealed that 11 mu g/g dw DBDPE significantly inhibited the development of silkworms. After DBDPE exposure, the intestinal tissue structure was significantly damaged. Furthermore, DBDPE exposure had a notably impact on the composition of the intestinal microbiota. Further RNA-seq analysis demonstrated that the transcription profiles of silkworms were markedly altered following DBDPE exposure, which was associated with enriched oxidative stress and protein export processes, downregulated transmembrane transport processes, and a series of disordered metabolic processes. Finally, the significant Spearman's correlation emphasizes the role of intestinal microbiota in the metabolic/immune dysregulation processes of silkworms. Overall, our results are the first to assess the toxic effects of environmentally relevant DBDPE concentrations on the insect intestine.

Neuroinflammation is a hallmark of central nervous system injury caused by fluorosis; however, the regulatory relationship between intestinal microbial and fluoride-induced neuroinflammation remains unclear. Here, we aimed to evaluate the alleviating effect of short-chain fatty acids (SCFAs) on fluoride exposure-induced neuroinflammation in rats. In this study, it is demonstrated that the composition of colonic microbiota was disrupted in fluoride-exposed rats at both phylum and genus levels, and fluoride exposure decreased the number of positive cells per crypt, inhibited mucin secretion, and reduced the protein expression of MUC2 and TFF3, and tight junction proteins (Occludin and ZO-1) in the colon tissue, leading to colonic mucosal barrier damage. Additionally, the content of IL-1β, TNF-α and LPS in the serum of fluoride-exposed rats was increased, and the TLR4/NF-κB pathway was also activated in the colon tissue. Moreover, the expression of Occludin and ZO-1 in the cerebral cortex was decreased by fluoride exposure, resulting in neuronal damage, astrocyte and microglial activation and the activation of the TLR4/NF-κB signaling pathway, which subsequently induced neuroinflammation. However, these adverse effects were mitigated by supplementation with SCFAs. It was observed that supplementation with SCFAs improves microbial dysbiosis in the colon, and SCFAs enhance tight junction integrity between intestinal epithelial cells, decrease intestinal permeability and the content of IL-1β, TNF-α and LPS in the serum, inhibit colonic inflammation. Additionally, SCFAs restored the damaged blood-brain barrier structure, suppressed astrocyte and microglial activation, and relieved fluoride-induced neuroinflammation by inhibiting the activation of the TLR4/NF-κB signaling pathway. In conclusion, SCFAs supplementation alleviates fluoride-induced colonic barrier damage and microbial disturbances, thereby mitigating fluoride-induced neuroinflammation in rats through the microbiota-gut-brain axis.

This study aimed to investigate the effects of dietary fluoride (F) and curcumin (Cur) supplementation on the tibial biomechanical performance, histopathology, and behavior of pullets. Four dietary F levels (0, 400, 800, 1200 mg/kg) supplemented with CUR (0, 200 mg/kg) were used to create 8 experimental groups in Hyline Brown pullets. Behavioral study results showed that supplements of 1200 mg/kg F reduced the percentages of feeding, walking, standing, and preening behaviors while increasing the percentage of lying behavior (P < 0.05). This is associated with F-induced tibial elastic modulus, maximum stress, and stiffness coefficient were reduced and toughness coefficient was increased (P < 0.05). F-induced tibial cortical bone thickened, trabecular bone widened, and excessive accumulation of bone collagen fibers (P< 0.05) in the tibia explained the biomechanical properties reduction in Hyline Brown pullets. Additionally, the loss of antioxidant capacity was mediated by excessive F-accelerated pathological damage to the bone (P < 0.05). Supplementation with 200 mg/kg CUR alleviated abnormal behavior, expansion of the trabecular bone, accumulation of collagen fibers, and loss of antioxidant capacity (P < 0.05). In conclusion, F reduced the antioxidant level of the body, caused tibia histopathological damage, destroyed the tibia biomechanical properties, and caused abnormal behavior of pullets. Supplementation with 200mg/kg CUR attenuates F-induced oxidative and tibia damage and rectifies abnormal behavioral traits.

The hepatotoxicity of microplastics (MPs) has garnered increasing attention, but their effects on elderly organisms remain inadequately characterized, particularly concerning hepatic stress response patterns in environmental conditions. In this study, a 10-day exposure period of elderly zebrafish to polystyrene microplastics (PS-MPs, 1 mu m) was conducted, with exposure concentrations set at 5.6 x 10-7 mu g/L, 5.6 x 10-4 mu g/L, and 5.6 x 10-1 mu g/L. PS-MPs-induced toxicity varied with concentration: superoxide dismutase (SOD), complement 3 (C3), and complement 4 (C4) initially decreased before rising; 8-hydroxy-2-deoxyguanosine (8-OhdG), interleukin-6 (IL-6), and interleukin-8 (IL-8) increased at high concentrations. Additionally, catalase (CAT) activity and thiobarbituric acid reactive substances (TBARS) contents rose with concentration. The aged zebrafish liver exhibited differentiation driven by responsiveness; low levels cause homeostatic disruption, and high levels induce genotoxicity and immune activation. LC-MS identified twelve crucial metabolites involved in 18 metabolic pathways, including amino acids (L-tyrosine, l-arginine), lipids (phospholipids, 12(S)-leukotriene B4 and triglycerides), and N-acetylneuraminic acid, related to energy, immunity, and neurological health. Overall, elderly zebrafish exhibited clear dose-dependent thresholds and distinct physiological stress responses under varying concentrations of PS-MPs. These findings reveal how PS-MP exposure can affect physiological health and metabolism, offering critical insights into the ecological risks faced by aging organisms.

Corneal injury can lead to visual impairment, and inflammation can significantly delay corneal injury repair. Therefore, anti-inflammatory therapy is crucial for the treatment of corneal injury. The work developed an ecofriendly strategy for the efficient preparative separation and purification of stilbenes and assess their effects on corneal injury repair using a mouse model. This novel process involved the use of ultrasound-assisted natural deep eutectic solvents (NaDESs) extraction, coupled with macroporous resins and preparative high-performance liquid chromatography (prep-HPLC). The optimal extraction process for stilbenes involved mixing the powdered C. candolleana roots (1.0 kg) with choline chloride/L-malic acid (1/1, molar ratio, water content 34.9 %) at a solid-liquid ratio of 126.2:1 mg/mL, followed by ultrasonication at 65 degrees C for 14.2 min three times. Resveratrol (C-1, 23.6 mg), epsilon-viniferin (C-2, 47.4 mg), and alpha-viniferin (C-3, 871.0 mg) were obtained through D101 resin and prep-HPLC. alpha-Viniferin and epsilon-viniferin significantly accelerated corneal epithelial healing compared to control in the mouse model, as shown by sodium fluorescein staining and hematoxylin-eosin staining. Immunofluorescence staining revealed that alpha-viniferin effectively inhibited the Akt/NF-kappa B signaling pathway. Quantitative real-time polymerase chain reaction confirmed the inhibitory effect of alpha-viniferin on the mRNA expression levels of pro- inflammatory factors. Consequently, these studies propose a new strategy for the preparation of stilbenes, among which, alpha-viniferin is effective in promoting corneal epithelial wound healing by targeting the Akt/NF-kappa B signaling pathway to inhibit inflammation, implying alpha-viniferin possesses promising potential as an alternative medication for treating corneal injury.

Fluoride, a common environmental pollutant in drinking water and air, poses a major public health risk in endemic regions. Fluorosis disrupts bone structure and density and impairs key physiological processes, including calcium-phosphorus homeostasis, hormone regulation, enzyme activity, and cytokine-mediated signaling—thereby compromising skeletal integrity. This review explores the molecular mechanisms through which chronic environmental fluoride exposure disrupts bone metabolism, leading to structural and functional skeletal damage. Chronic fluoride exposure alters bone mineral crystals due to its high affinity for calcium, reducing mechanical strength and disturbing phosphorus balance. It also inhibits vitamin D hydroxylation, decreasing active vitamin D bioavailability and impairing calcium and phosphorus absorption. Fluoride disrupts endocrine homeostasis by altering secretion of parathyroid hormone, calcitonin, and estrogen. At the enzymatic level, it modulates alkaline phosphatase, acid phosphatase, and matrix metalloproteinases, affecting osteoblast/osteoclast function and bone remodeling. Furthermore, fluorosis modulates cytokine networks, influencing irisin, osteopontin, and hypoxia-inducible factor-α—key regulators of bone metabolism. These insights are vital for environmental health risk assessment and the development of targeted prevention and therapeutic strategies. Future research should clarify these pathways to better address fluorosis-induced skeletal disorders.

Our previous studies have demonstrated that fluoride (F) overexposure is a risk factor for colonic microenvironment, yet its underlying mechanisms and the influencing factors remain poorly understood. Here, a rat model of F exposure (0, 25, 50, 100 mg/L in drinking water) combined with ovariectomy (OVX)-induced estrogen deficiency was established to investigate the roles of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in F-induced colonic damage under the state of estrogen deficiency. Result showed that F exposure significantly reduced occludin and claudin-1 expression, further resulting in the colon's morphology impairment. Concurrently, F suppressed epithelial proliferation, decreased goblet cell numbers, and diminished short-chain fatty acid (SCFA) production. OVX-induced estrogen deficiency exacerbated F-induced colonic barrier damage and SCFA decreased. Mechanistically, estrogen deficiency aggravated F intestinal toxicity by further inhibiting the protein expression of Nrf2 and HO-1 and upregulating Keap1 protein expression, following downregulated Bcl-2 mRNA levels and upregulated Bax and caspase-3 mRNA levels, and promoting colonic epithelial cell apoptosis. These findings identify that Nrf2/HO-1 key protein disorders are involved in F-induced colonic barrier injury, and estrogen deficiency further aggravated F intestinal toxicity.

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.

BackgroundThe vulnerable period to neurotoxicity of isoflurane overlaps with a developmental stage characterized by programmed neuronal death. STAT3 has been identified as a crucial molecule involved in survival pathways during this period. We aimed to investigate the role of STAT3 in cellular vulnerability to isoflurane.MethodsC57/BL6 mice on postnatal day 7 or 21, primary neurons derived from mice embryos at gestational days 14-16 and cultured for 5 or 14 days, as well as human neuroglioma U251 cells were treated with isoflurane. A plasmid containing human wild-type STAT3, STAT3 anti-sense oligonucleotide, STAT3 specific inhibitor STA21, proteasome inhibitor MG-132 and calcineurin inhibitor FK506 were utilized to evaluate the influence of STAT3 levels on isoflurane-induced cytotoxicity. The levels of Western blot results, mRNA, intracellular ROS, apoptotic rate, and calcineurin activity were analyzed using unpaired Student's t-test or one-way ANOVA followed by Bonferroni post hoc test, as appropriate.ResultsElevated levels of STAT3, reduced activity of calcineurin, as well as a diminished response to isoflurane-induced calcineurin activation and neuroapoptosis were observed in more mature brain or neurons. Isoflurane accelerated the degradation of ubiquitin-conjugated proteins but did not facilitate ubiquitin conjugation to proteins. STAT3 was of particular importance in the all ubiquitin-conjugated proteins degraded by isoflurane. Knockdown or inhibition of STAT3 nuclear translocation exacerbated isoflurane-induced oxidative injury and apoptosis, while STAT3 overexpression mitigated these effects. Finally, this study demonstrated that FK506 pretreatment mitigated the apoptosis, ROS accumulation, and the impairment of neurite growth in primary neurons after exposed to isoflurane.ConclusionsThese findings indicate that specific regulation of STAT3 was closely related with the cellular vulnerability to isoflurane via an antioxidative pathway.

Microplastic (MP) toxicity has attracted widespread attention, whereas before triggering hepatotoxicity, ingested MPs first undergo transportation and digestion processes in the gastrointestinal tract, possibly interacting with the gastrointestinal contents (GIC). More alarming is the need for more understanding of how this process may impact the liver health of aged animals. This study selected old mice. Firstly, we incubated polystyrene microplastics (PS-MPs, 1 mu m) with GIC extract. The results of SEM/EDS indicated a structural alteration in PS-MPs. Additionally, impurities resembling corona, rich in heteroatoms (O, N, and S), were observed. This resulted in an enhanced aggregating phenomenon of MPs. We conducted a 10-day experiment exposing aged mice to four concentrations of PS-MPs, ranging from 1 x 103 to 1 x 1012 particles/L. Subsequent measurements of tissue pathology and body and organ weights were conducted, revealing alterations in liver structure. In the liver, 12 crucial metabolites were found by LC-MS technology, including purines, lipids, and amino acids. The AMPK/ FoxO pathway was enriched, activated, and validated in western blotting results. We also comprehensively examined the innate immune system, inflammatory factors, and oxidative stress indicators. The results indicated decreased C3 levels, stable C4 levels, inflammatory factors (IL-6 and IL-8), and antioxidant enzymes were increased to varying degrees. PS-MPs also caused DNA oxidative damage. These toxic effects exhibited a specific dose dependence. Overall, after the formation of the gastrointestinal corona, PS-MPs subsequently impact various cellular processes, such as cycle arrest (p21), leading to hepatic and health crises in the elderly. The presence of gastrointestinal coronas also underscores the MPs' morphology and characteristics, which should be distinguished after ingestion.

BACKGROUND:Molybdenum (Mo) plays a crucial role in regulating normal physiological function. However, its potential effect on female infertility has received little attention. METHODS:In this study, we explored the potential molecular mechanisms of Mo's action on mouse ovaries and oocytes by establishing a busulfan-induced infertility model. Adult female Kunming mice were randomly divided into three groups: control, +busulfan, and +busulfan+Mo. After 30 days of busulfan treatment [Myleran, 20 mg/kg body weight ip], mice in the busulfan+Mo group were provided with 7.5 mg/L Mo per day in drinking water for an additional 42 days. On day 72, we examined the morphology of the oocytes and ovarian tissue after H&E staining, measured the concentrations of serum hormones by ELISA, and detected Bax, Bcl-2, caspase-3 and caspase-9 by immunohistochemical staining and western immunoblotting. We also assessed the oxidative stress in cells by measuring the activity of the antioxidant enzyme, SOD, the concentrations of MDA and LDH, and the percentage of apoptotic cells using kits. The number of litters born was counted after mating with male mice, and the organ coefficients were calculated after weighing on an analytic balance. RESULTS:Results showed that Mo treatment restored female reproductive hormone levels to near normal. Mo also significantly inhibited the mitochondrial stress-induced expression of apoptotic proteins. CONCLUSION:Our findings demonstrate that Mo treatment at a dose of 7.5 mg/L can ameliorate busulfan-induced infertility in female mice. These data may provide a reference for the development of treatments for female infertility.

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.