Highly Ionic Conductive, Stretchable, and Tough Ionogel for Flexible Solid-State Supercapacitor.

The increasing demand for wearable electronics calls for advanced energy storage solutions that integrate high  electrochemical performances and mechanical robustness. Ionogel is a promising candidate due to its stretchability combined with high ionic conductivity. However, simultaneously optimizing both the electrochemical and mechanical performance of ionogels remains a challenge. This paper reports a tough and highly ion-conductive ionogel through ion impregnation and solvent exchange. The fabricated ionogel consists of double interpenetrating networks of long polymer chains that provide high stretchability. The polymer chains are crosslinked by hydrogen bonds that induce large energy dissipation for enhanced toughness. The resultant ionogel possesses mechanical stretchability of 26, tensile strength of 1.34 MPa, and fracture toughness of 4175 J m-2. Meanwhile, due to the high ion concentrations and ion mobility in the gel, a high ionic conductivity of 3.18 S m-1 at room temperature is achieved. A supercapacitor of this ionogel sandwiched with porous fiber electrodes provides remarkable areal capacitance (615 mF cm-2 at 1 mA cm-2), energy density (341.7 µWh cm-2 at 1 mA cm-2), and power density (20 mW cm-2 at 10 mA cm-2), offering significant advantages in applications where high efficiency, compact size, and rapid energy delivery are crucial, such as flexible and wearable electronics.

Teaching diagnostic radiology to radiology majors: Implementation and evaluation of a flipped classroom model.

PURPOSE: Radiology instruction focuses on cultivating medical students' diagnostic thinking skills and practical competence, and lecture-based learning (LBL) is the most commonly used teaching approach. While fact-based, this type of traditional instruction is often non-engaging, leading to a shift toward student-centered models, one of which is the flipped classroom (FC). However, studies involving a comprehensive evaluation of students' experiences using the FC approach and its effects on their learning are lacking. Therefore, this study analyzed the teaching efficacy of the FC approach based on data of large groups of radiology students, accumulated over time. METHODS: Data from 636 medical radiology students taught using the FC and LBL models from 2012 to 2021 were retrospectively collected and analyzed. RESULTS: The test scores of the FC group were significantly higher than those of the LBL group, and improvements in learning initiative and learning ability were notably higher in the FC than in the LBL group. The two groups showed no significant difference in the critical thinking disposition indicator, and the proportion of students with positive critical thinking tendencies was higher in the FC than in the LBL group. The academic and social self-perception scores of the FC group were significantly higher than those of the LBL group, and there was a significant difference in Kolb's learning style. CONCLUSIONS: Based on evidence of completing pre-, in-, and after-class work, the FC approach improved students' academic performance, learning initiative, diagnostic ability, and satisfaction with learning and the teaching institution. Our findings suggest that FC instruction promotes students' assimilation and convergence of learning styles, and cultivates positive critical thinking.

Enhancing Lithium Stripping Efficiency in Anode-Free Solid-State Batteries through Self-Regulated Internal Pressure.

Anode-free all-solid-state lithium metal batteries (ASLMBs) promise high energy density and safety but suffer from a low initial Coulombic efficiency and rapid capacity decay, especially at high cathode loadings. Using operando techniques, we concluded these issues were related to interfacial contact loss during lithium stripping. To address this, we introduce a conductive carbon felt elastic layer that self-adjusts the pressure at the anode side, ensuring consistent lithium-solid electrolyte contact. This layer simultaneously provides electronic conduction and releases the plating pressure. Consequently, the first Coulombic efficiency dramatically increases from 58.4% to 83.7% along with a >10-fold improvement in cycling stability. Overall, this study reveals an approach for enhancing anode-free ASLMB performance and longevity by mitigating lithium stripping inefficiency through self-adjusting interfacial pressure enabled by a conductive elastic interlayer.

Hydrocarbons in the Meniscus: Effects on Conductive Atomic Force Microscopy.

It is commonly accepted that during conductive atomic force microscopy (CAFM) measurement in ambient, a liquid meniscus can form between the tip and the sample. Such a liquid bridge, normally assumed to be composed of water, is a major factor in analyzing and understanding CAFM results. Here, we show that the adsorption of adventitious hydrocarbons from the air to a surface can greatly affect CAFM data both in imaging mode and in local spectroscopy (current-voltage or I-V curves). We propose a model to explain the phenomena whereby hydrocarbon contaminates contribute to the composition of the liquid bridge between the tip and the sample.

Influence of Atmospheric Contaminants on the Work Function of Graphite.

Airborne hydrocarbon contamination occurs rapidly on graphitic surfaces and negatively impact many of their material properties, yet much of the molecular details of the contamination remains unknown. We use Kelvin probe force microscopy (KPFM) to study the time evolution of the surface potential of graphite exposed to ambient. After exfoliation in air, the surface potential of graphite is not homogeneous and contains features that are absent in the topography image. In addition, the heterogeneity of the surface potential images increased in the first few days followed by a decrease at longer exposure times. These observations are strong support of slow conformation change, phase separation, and/or dynamic displacement of the adsorbed airborne contaminants.

Polystyrene nanoplastic exposure induces excessive mitophagy by activating AMPK/ULK1 pathway in differentiated SH-SY5Y cells and dopaminergic neurons in vivo.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging environmental contaminants detected in human samples, and have raised concerns regarding their potential risks to human health, particularly neurotoxicity. This study aimed to investigate the deleterious effects of polystyrene nanoplastics (PS-NPs, 50 nm) and understand their mechanisms in inducing Parkinson's disease (PD)-like neurodegeneration, along with exploring preventive strategies. METHODS: Following exposure to PS-NPs (0.5-500 µg/mL), we assessed cytotoxicity, mitochondrial integrity, ATP levels, and mitochondrial respiration in dopaminergic-differentiated SH-SY5Y cells. Molecular docking and dynamic simulations explored PS-NPs' interactions with mitochondrial complexes. We further probed mitophagy's pivotal role in PS-NP-induced mitochondrial damage and examined melatonin's ameliorative potential in vitro. We validated melatonin's intervention (intraperitoneal, 10 mg/kg/d) in C57BL/6 J mice exposed to 250 mg/kg/d of PS-NPs for 28 days. RESULTS: In our in vitro experiments, we observed PS-NP accumulation in cells, including mitochondria, leading to cell toxicity and reduced viability. Notably, antioxidant treatment failed to fully rescue viability, suggesting reactive oxygen species (ROS)-independent cytotoxicity. PS-NPs caused significant mitochondrial damage, characterized by altered morphology, reduced mitochondrial membrane potential, and decreased ATP production. Subsequent investigations pointed to PS-NP-induced disruption of mitochondrial respiration, potentially through interference with complex I (CI), a concept supported by molecular docking studies highlighting the influence of PS-NPs on CI. Rescue experiments using an AMPK pathway inhibitor (compound C) and an autophagy inhibitor (3-methyladenine) revealed that excessive mitophagy was induced through AMPK/ULK1 pathway activation, worsening mitochondrial damage and subsequent cell death in differentiated SH-SY5Y cells. Notably, we identified melatonin as a potential protective agent, capable of alleviating PS-NP-induced mitochondrial dysfunction. Lastly, our in vivo experiments demonstrated that melatonin could mitigate dopaminergic neuron loss and motor impairments by restoring mitophagy regulation in mice. CONCLUSIONS: Our study demonstrated that PS-NPs disrupt mitochondrial function by affecting CI, leading to excessive mitophagy through the AMPK/ULK1 pathway, causing dopaminergic neuron death. Melatonin can counteract PS-NP-induced mitochondrial dysfunction and motor impairments by regulating mitochondrial autophagy. These findings offer novel insights into the MNP-induced PD-like neurodegenerative mechanisms, and highlight melatonin's protective potential in mitigating the MNP's environmental risk.

Prenatal diagnosis of megaduodenum using ultrasound: a case report.

BACKGROUND: Congenital megaduodenum is a rare disorder; however, its prenatal diagnosis has not been reported previously. We report the case of an abdominal cystic mass in a fetus that was later diagnosed as megaduodenum. CASE PRESENTATION: An abdominal cystic mass was found during ultrasonography of a fetus at 11 weeks of gestation. The mass progressively enlarged with gestation. The amniotic fluid volume decreased and then returned to normal. During the last prenatal ultrasound examination, the mass was observed communicating with the stomach; therefore, duodenal dilation was suspected. Finally, the patient was diagnosed with megaduodenum caused by a developmental defect in the nerve plexus. CONCLUSIONS: Congenital megaduodenum is a differential diagnosis of massive fetal abdominal cystic masses. Ultrasound examinations of such masses communicating with the stomach may help determine the diagnosis.

Lactic acid, neuron-specific enolase, and blood-brain barrier index after a severe traumatic brain injury: a prospective study.

OBJECTIVE: To explore the clinical significance of dynamic monitoring of cerebrospinal fluid (CSF) and serum Lactic acid（Lac), neuron-specific enolase (NSE), and the blood-brain barrier (BBB) index in evaluating the condition and prognosis after a severe traumatic brain injury (TBI). METHODS: A total of 52 severe TBI patients admitted to the Department of Neurosurgery within 24 hours after injury were dynamically monitored. CSF and serum samples were collected on the 1st, 3rd, and 7th day after a severe TBI to monitor the changes in Lac, NSE, and the BBB index. Intracranial pressure (ICP), Glasgow coma scale (GCS), and 6-month Glasgow outcome scale-extended (GOS-E) were tested. According to the results of GOS-E, the patients were divided into two groups (i.e. the poor prognosis group and good prognosis group). Statistical analysis was conducted to investigate the clinical significance of dynamic monitoring of CSF and serum Lac, NSE, and BBB index after a severe TBI. RESULTS: After a severe TBI, the levels of Lac, NSE, and BBB in CSF and serum were significantly higher than those in the normal range. Lac, NSE, and the BBB index did not correlate with ICP (except serum Lac) but had correlations with GCS and post-injury 6 months post-injury (except serum Lac). Moreover, the correlations between Lac, NSE, and BBB index were statistically significant (p < 0.05): CSF Lac and CSF NSE; CSF Lac and serum NSE; Lac and BBB index of CSF; Lac and BBB index of CSF; NSE and CSE of serum; CSF NSE and BBB index; and serum NSE and BBB index. Additionally, serum NSE is correlated with NSE in CSF (p < 0.05). CONCLUSION: After a severe TBI, dynamic monitoring of CSF and serum Lac, NSE, and BBB index has the potential to assess the condition, predict the prognosis, and have clinical significance.

Flaw-Insensitive Hydrogels under Static and Cyclic Loads.

New applications of hydrogels draw growing attention to the development of tough hydrogels. Most tough hydrogels are designed through incorporating large energy dissipation from breaking sacrificial bonds. However, these hydrogels still fracture under prolonged cyclic loads with the presence of even small flaws. This paper presents a principle of flaw-insensitive hydrogels under both static and cyclic loads. The design aligns the polymer chains in a hydrogel at the molecular level to deflect a crack. To demonstrate this principle, a hydrogel of polyacrylamide and polyvinyl alcohol is prepared with aligned crystalline domains. When the hydrogel is stretched in the direction of alignment, an initial flaw deflects, propagates along the loading direction, peels off the material, and leaves the hydrogel flawless again. The hydrogel is insensitive to pre-existing flaws, even under more than ten thousand loading cycles. The critical degree of anisotropy to achieve crack deflection is quantified by experiments and fracture mechanics. The principle can be generalized to other hydrogel systems.

Fatigue fracture of nearly elastic hydrogels.

Polyacrylamide hydrogels are highly stretchable and nearly elastic. Their stress-stretch curves exhibit small hysteresis, and change negligibly after many loading cycles. Polyacrylamide is used extensively in applications, and is the primary network for many types of tough hydrogels. Recent experiments have shown that polyacrylamide hydrogels are susceptible to fatigue fracture, but available data are limited. Here we study fatigue fracture of polyacrylamide hydrogels of various water contents. We form polymer networks in all samples under the same conditions, and then obtain hydrogels of 96, 87, 78, and 69 wt% of water by solvent exchange. We measure the crack extension under cyclic loads, and the fracture energy under monotonic loading. For the hydrogels of the four water contents, the fatigue thresholds are 4.3, 8.4, 20.5, and 64.5 J m-2, and the fracture energies are 18.9, 71.2, 289, and 611 J m-2. The measured thresholds agree well with the predictions of the Lake-Thomas model for hydrogels of high water content, but not in the case of low water content. It is hoped that further basic studies will soon follow to aid the development of fatigue-resistant hydrogels.

Molecular-Curvature-Induced Spontaneous Formation of Curved and Concentric Lamellae through Nucleation.

Spontaneous formation of concentric lamellae was observed in self-assembling giant surfactants consisting of a fluorinated polyhedral oligomeric silsesquioxane (FPOSS) head and flexible polymer tail(s). Owing to the asymmetrical sizes of the head and tail blocks and the rectangular molecular interface, the giant surfactants assumed a truncated-wedge-like molecular shape, which induced morphological curvature during self-assembly, thus resulting in the formation of curved and concentric lamellae. These curved/concentric lamellae were observed in FPOSS-based giant surfactants with different architectures and compositions. The spontaneous curvature formation not only promotes our fundamental understanding of assembly principles, but also provides a promising and efficient approach to the fabrication of a wide range of high-performance devices.

Association of liver multi-parameter quantitative metrics determined by dual-layer spectral detector computed tomography (SDCT) with coronary plaque scores.

Background: Hepatic steatosis is closely related to the occurrence and development of coronary plaques. Spectral detector computed tomography (SDCT) can provide more precise multiparameter quantitative parameters for hepatic steatosis. Hence, the purpose of this cross-sectional study was to explore the effect of quantitative liver metrics measured using SDCT on the extent and severity of coronary plaques. Methods: In patients who underwent upper abdomen unenhanced SDCT and coronary computed tomography angiography, plaque extent and severity were assessed using segmental involvement score (SIS) and segmental stenosis score (SSS). Liver fat quantification was evaluated by polychromatic and virtual mono-energetic images at 40 and 70 kev, spectral attenuation curve slope, and effective atomic number (CT40 keV, CT70 kev, λHU, and Zeff, respectively). A logistic regression model evaluated the factors influencing high SIS and SSS. Results: Enrolled patients (n=644) were divided into groups: low SIS (<5) (n=451), high SIS (≥5) (n=193), low SSS (<5) (n=461), and high SSS (≥5) (n=183). Zeff was more closely correlated with SIS (standard partial regression coefficient =-0.422, P<0.001) and SSS (standard partial regression coefficient =-0.346, P<0.001). Zeff was divided into four groups using interquartile intervals. Compared with the patients in the lowest quartile, those in the second [odds ratio (OR) =2.116, 95% confidence interval (CI): 1.134-3.949, P=0.018], third (OR =2.832, 95% CI: 1.461-5.491, P=0.002), and fourth (OR =3.584, 95% CI: 1.857-6.918, P<0.001) quartiles showed higher risk for high SIS. And correspondingly, the second (OR =1.933, 95% CI: 1.040-3.592, P=0.037), third (OR =2.900, 95% CI: 1.499-5.609, P=0.002), and fourth (OR =3.368, 95% CI: 1.743-6.510, P<0.001) quartiles showed higher risk for high SSS, especially in those who were <60 years old, male and had visceral adipose tissue/subcutaneous adipose tissue <1.18. Conclusions: The SDCT-Zeff was an independent factor associated with high SIS and SSS. The quantification of liver fat may be useful for evaluating the risk and prognosis of coronary atherosclerosis.

The clinical significance of mitochondrial calcium uniporter in gastric cancer patients and its preliminary exploration of the impact on mitochondrial function and metabolism.

Objective: The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. Methods: Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis. Data from TCGA, GTEx and GEO databases were retrieved for gastric cancer patients, and bioinformatics analysis was utilized to investigate the association between MCU expression and clinical pathological features. Furthermore, we conducted an in-depth analysis of the role of MCU in GC patients. We investigated the correlation between MCU expression in GC and its impact on mitochondrial function, metabolism, biosynthesis, and immune cells. Additionally, we studied the proteins or molecules that interact with MCU. Results: Our research revealed high expression of MCU in the GC tissues. This high expression was associated with poorer T and N staging, and indicated a worse disease-free survival period. MCU expression was positively correlated with mitochondrial function, mitochondrial metabolism, nucleotide, amino acid, and fatty acid synthesis metabolism, and negatively correlated with nicotinate and nicotinamide metabolism. Furthermore, the MCU also regulates the function of the mitochondrial oxidative respiratory chain. The MCU influences the immune cells of GC patients and regulates ROS generation, cell proliferation, apoptosis, and resistance to platinum-based drugs in gastric cancer cells. Conclusion: High expression of MCU in GC indicates poorer clinical outcomes. The expression of the MCU are affected through impacts the function of mitochondria, energy metabolism, and cellular biosynthesis in gastric cancer cells, thereby influencing the growth and metastasis of gastric cancer cells. Therefore, the mitochondrial changes regulated by MCU could be a new focus for research and treatment of GC.

Dual-layer spectral-detector CT for detecting liver steatosis by using proton density fat fraction as reference.

OBJECTIVES: To evaluate the diagnostic accuracy of liver dual-layer spectral-detector CT (SDCT) derived parameters of liver parenchyma for grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). METHODS: Altogether, 320 consecutive subjects who underwent MRI-PDFF and liver SDCT examinations were recruited and prospectively enrolled from four Chinese hospital centers. Participants were classified into normal (n = 152), mild steatosis (n = 110), and moderate/severe(mod/sev) steatosis (n = 58) groups based on MRI-PDFF. SDCT liver parameters were evaluated using conventional polychromatic CT images (CTpoly), virtual mono-energetic images at 40 keV (CT40kev), the slope of the spectral attenuation curve (λ), the effective atomic number (Zeff), and liver to spleen attenuation ratio (L/S ratio). Linearity between SDCT liver parameters and MRI-PDFF was examined using Spearman correlation. Cutoff values for SDCT liver parameters in determining steatosis grades were identified using the area under the receiver-operating characteristic curve analyses. RESULTS: SDCT liver parameters demonstrated a strong correlation with PDFF, particularly Zeff (rs = -0.856; p < 0.001). Zeff achieved an area under the curve (AUC) of 0.930 for detecting the presence of steatosis with a sensitivity of 89.4%, a specificity of 82.4%, and an AUC of 0.983 for detecting mod/sev steatosis with a sensitivity of 93.1%, a specificity of 93.5%, the corresponding cutoff values were 7.12 and 6.94, respectively. Zeff also exhibited good diagnostic performance for liver steatosis grading in subgroups, independent of body mass index. CONCLUSION: SDCT liver parameters, particularly Zeff, exhibit excellent diagnostic accuracy for grading steatosis. CRITICAL RELEVANCE STATEMENT: Dual-layer SDCT parameter, Zeff, as a more convenient and accurate imaging biomarker may serve as an alternative indicator for MRI-based proton density fat fraction, exploring the stage and prognosis of liver steatosis, and even metabolic risk assessment. KEY POINTS: Liver biopsy is the standard for grading liver steatosis, but is limited by its invasive nature. The diagnostic performance of liver steatosis using SDCT-Zeff outperforms conventional CT parameters. SDCT-Zeff accurately and noninvasively assessed the grade of liver steatosis.

Fragile Guts Make Fragile Brains: Intestinal Epithelial Nrf2 Deficiency Exacerbates Neurotoxicity Induced by Polystyrene Nanoplastics.

Oral ingestion is the primary route for human exposure to nanoplastics, making the gastrointestinal tract one of the first and most impacted organs. Given the presence of the gut-brain axis, a crucial concern arises regarding the potential impact of intestinal damage on the neurotoxic effects of nanoplastics (NPs). The intricate mechanisms underlying NP-induced neurotoxicity through the microbiome-gut-brain axis necessitate further investigation. To address this, we used mice specifically engineered with nuclear factor erythroid-derived 2-related factor 2 (Nrf2) deficiency in their intestines, a strain whose intestines are particularly susceptible to polystyrene NPs (PS-NPs). We conducted a 28-day repeated-dose oral toxicity study with 2.5 and 250 mg/kg of 50 nm PS-NPs in these mice. Our study delineated how PS-NP exposure caused gut microbiota dysbiosis, characterized by Mycoplasma and Coriobacteriaceae proliferation, resulting in increased levels of interleukin 17C (IL-17C) production in the intestines. The surplus IL-17C permeated the brain via the bloodstream, triggering inflammation and brain damage. Our investigation elucidated a direct correlation between intestinal health and neurological outcomes in the context of PS-NP exposure. Susceptible mice with fragile guts exhibited heightened neurotoxicity induced by PS-NPs. This phenomenon was attributed to the elevated abundance of microbiota associated with IL-17C production in the intestines of these mice, such as Mesorhizobium and Lwoffii, provoked by PS-NPs. Neurotoxicity was alleviated by in vivo treatment with anti-IL-17C-neutralizing antibodies or antibiotics. These findings advanced our comprehension of the regulatory mechanisms governing the gut-brain axis in PS-NP-induced neurotoxicity and underscored the critical importance of maintaining intestinal health to mitigate the neurotoxic effects of PS-NPs.

Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation.

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

1,2-Dichloroethane induces testicular pyroptosis by activating piR-mmu-1019957/IRF7 pathway and the protective effects of melatonin.

1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish.

BACKGROUND: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. OBJECTIVES: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo. METHODS: We assessed the impact of polystyrene nanospheres (PNSs; 50 nm, 1.0mg/L) on HMS-induced MCF-7 cell proliferation (HMS: 0.01-1µM, equivalent to 2.62-262µg/L) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS (0.0262-262µg/L) with or without PNSs (50 nm, 1.0mg/L) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus-pituitary-gonad-liver (HPGL) axis. RESULTS: Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor α (ESR1) and the mRNAs of target genes (pS2, AREG, and PGR), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of SGK1 and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes (cyp17a2, hsd17[Formula: see text]1, esr2b, vtg1, and vtg2), and resulted in higher 17ß-estradiol (E2) release in females. Conversely, males showed lower testosterone, E2, and gene expressions of cyp11a1, cyp11a2, cyp17a1, cyp17a2, and hsd17[Formula: see text]1. DISCUSSION: PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.