Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.

BACKGROUND: Dysregulation of iron metabolism is implicated in malignant transformation, cancer progression, and therapeutic resistance. Here, we demonstrate that iron regulatory protein 2 (IRP2) preferentially regulates iron metabolism and promotes tumor growth in colorectal cancer (CRC). METHODS: IRP2 knockdown and knockout cells were generated using RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 methodologies, respectively. Cell viability was evaluated using both CCK-8 assay and cell counting techniques. Furthermore, IRP2 inhibition was determined by surface plasmon resonance (SPR) and RNA immunoprecipitation (IP). The suppressive effects of IRP2 were also corroborated in both organoid and mouse xenograft models, providing a comprehensive validation of IRP2's role. RESULTS: We have elucidated the role of IRP2 as a preferential regulator of iron metabolism, actively promoting tumorigenesis within CRC. Elevated levels of IRP2 expression in patient samples are correlated with diminished overall survival, thereby reinforcing its potential role as a prognostic biomarker. The functional suppression of IRP2 resulted in a pronounced delay in tumor growth. Building on this proof of concept, we have developed IRP2 inhibitors that significantly reduce IRP2 expression and hinder its interaction with iron-responsive elements in key iron-regulating proteins, such as ferritin heavy chain 1 (FTH1) and transferrin receptor (TFRC), culminating in iron depletion and a marked reduction in CRC cell proliferation. Furthermore, these inhibitors are shown to activate the AMPK-ULK1-Beclin1 signaling cascade, leading to cell death in CRC models. CONCLUSIONS: Collectively, these findings highlight the therapeutic potential of targeting IRP2 to exploit the disruption of iron metabolism in CRC, presenting a strategic advancement in addressing a critical area of unmet clinical need.

Ion Release and Apatite Formation of Resin Based Pit and Fissure Sealants Containing 45S5 Bioactive Glass.

The purpose of this study was to evaluate a resin based pit and fissure sealant containing 45S5 bioactive glass (BAG) by examining its ion release, pH variation, and apatite-forming properties. To prepare the experimental materials, 45S5 BAG, used as a filler, was incorporated into the light curable resin matrix at concentrations of 0 (control), 12.5, 37.5, and 50.0 wt.%. Ion release, pH variation, and apatite formation (Raman spectrometer and scanning electron microscopy-energy-dispersive X-ray spectrometry measurements) were performed. While no ions were released from the control group, the experimental groups containing 45S5 BAG showed an increased release of Ca and P ions with increasing amounts of 45S5 BAG (p < 0.05). The pH of the experimental group remained high and was significantly different from the control group (p < 0.05). Unlike the control group, it was confirmed that the apatite peak was formed in the 50.0 wt.% BAG group for 90 days, and the apatite layer consisting of Ca and P was deposited on the surface. Thus, a resin based pit and fissure sealant containing 45S5 BAG is a promising material for preventing secondary caries by releasing ions and forming apatite.

Targeted delivery of anti-miRNA21 sensitizes PD-L1high tumor to immunotherapy by promoting immunogenic cell death.

Rationale: Growing evidence has demonstrated that miRNA-21 (miR-21) upregulation is closely associated with tumor pathogenesis. However, the mechanisms by which miR-21 inhibition modulates the immunosuppressive tumor microenvironment (TME) and improves tumor sensitivity to immune checkpoint blockade therapies remain largely unexplored. In this study, we demonstrate the precise delivery of anti-miR-21 using a PD-L1-targeting peptide conjugate (P21) to the PD-L1high TME. Methods: Investigating miR-21 inhibition mechanisms involved conducting quantitative real-time PCR, western blot, flow cytometry, and confocal microscopy analyses. The antitumor efficacy and immune profile of P21 monotherapy, or combined with anti-PD-L1 immune checkpoint inhibitors, were assessed in mouse models bearing CT26.CL25 tumors and 4T1 breast cancer. Results Inhibition of oncogenic miR-21 in cancer cells by P21 efficiently activates tumor suppressor genes, inducing autophagy and endoplasmic reticulum stress. Subsequent cell-death-associated immune activation (immunogenic cell death) is initiated via the release of damage-associated molecular patterns. The in vivo results also illustrated that the immunogenic cell death triggered by P21 could effectively sensitize the immunosuppressive TME. That is, P21 enhances CD8+ T cell infiltration in tumor tissues by conferring immunogenicity to dying cancer cells and promoting dendritic cell maturation. Meanwhile, combining P21 with an anti-PD-L1 immune checkpoint inhibitor elicits a highly potent antitumor effect in a CT26.CL25 tumor-bearing mouse model and 4T1 metastatic tumor model. Conclusions: Collectively, we have clarified a miR-21-related immunogenic cell death mechanism through the precise delivery of anti-miR-21 to the PD-L1high TME. These findings highlight the potential of miR-21 as a target for immunotherapeutic interventions.

Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates.

Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. We developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) in monkeys. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys measurement sensors which may lead to misclassification of these signals as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. We identified and discriminated cell type-specific units in the monkey striatum that were shown to correlate to specific behavioral task parameters related to reward size and eye movement direction. Synchronously recorded spike and dopamine signals displayed contrasting relations to the task variables, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.

Myricetin ameliorates the severity of pancreatitis in mice by regulating cathepsin B activity and inflammatory cytokine production.

Cathepsin B (CTSB) and inflammatory cytokines are critical in initiating and developing pancreatitis. Calcineurin, a central calcium (Ca2+)-responsive signaling molecule, mediates acinar cell death and inflammatory responses leading to pancreatitis. However, the detailed mechanisms for regulating CTSB activity and inflammatory cytokine production are unknown. Myricetin (MC) exhibits various biological activities, including anti-inflammatory effects. Here, we aimed to investigate MC effects on pancreatitis and the underlying mechanisms. Prophylactic and therapeutic MC treatment ameliorated the severity of cerulein-, L-arginine-, and PDL-induced acute pancreatitis (AP). The inhibition of CTSB activity by MC was mediated via decreased calcineurin activity and macrophage infiltration, not neutrophils infiltration, into the pancreas. Additionally, calcineurin activity inhibition by MC prevented the phosphorylation of Ca2+/CaM-dependent protein kinase kinase 2 (CaMKK2) during AP, resulting in the inhibition of CaMKIV phosphorylation and adenosine monophosphate-activated protein kinase (AMPK) dephosphorylation. Furthermore, MC reduced nuclear factor-κB activation by modulating the calcineurin-CaMKIV-IKKα/ß-Iκ-Bα and calcineurin-AMPK-sirtuin1 axes, resulting in reduced production of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. Our results showed that MC alleviated AP severity by inhibiting acinar cell death and inflammatory responses, suggesting that MC as a calcineurin and CaMKK2 signaling modulator may be a potential treatment for AP.

Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

PURPOSE: This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. METHODS: The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. RESULTS: The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. CONCLUSION: The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Anti-Obesity Effect and Signaling Mechanism of Potassium Poly-γ-Glutamate Produced by Bacillus subtilis Chungkookjang in High-Fat Diet-Induced Obese Mice.

The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.

All-Solution-Processed High-Performance MoS2 Thin-Film Transistors with a Quasi-2D Perovskite Oxide Dielectric.

Assembling solution-processed van der Waals (vdW) materials into thin films holds great promise for constructing large-scale, high-performance thin-film electronics, especially at low temperatures. While transition metal dichalcogenide thin films assembled in solution have shown potential as channel materials, fully solution-processed vdW electronics have not been achieved due to the absence of suitable dielectric materials and high-temperature processing. In this work, we report on all-solution-processedvdW thin-film transistors (TFTs) comprising molybdenum disulfides (MoS2) as the channel and Dion-Jacobson-phase perovskite oxides as the high-permittivity dielectric. The constituent layers are prepared as colloidal solutions through electrochemical exfoliation of bulk crystals, followed by sequential assembly into a semiconductor/dielectric heterostructure for TFT construction. Notably, all fabrication processes are carried out at temperatures below 250 °C. The fabricated MoS2 TFTs exhibit excellent device characteristics, including high mobility (>10 cm2 V-1 s-1) and an on/off ratio exceeding 106. Additionally, the use of a high-k dielectric allows for operation at low voltage (∼5 V) and leakage current (∼10-11 A), enabling low power consumption. Our demonstration of the low-temperature fabrication of high-performance TFTs presents a cost-effective and scalable approach for heterointegrated thin-film electronics.

Understanding the caregiving experiences of Asian Indian, Chinese, Korean, and Vietnamese American family care partners of persons living with dementia.

OBJECTIVES: Disparities impacting dementia health care exist in racial/ethnic minority groups, including Asian Americans, an understudied population in Alzheimer's disease and related dementias. The qualitative study explored caregiving experiences and potential cultural influences among Asian Indian, Chinese, Korean, and Vietnamese family care partners of persons living with dementia. METHODS: We conducted focus groups and individual interviews with 32 care partners from these four Asian subgroups using Zoom, WeChat, or telephone. RESULTS: Four themes emerged from the data: (1) Family obligations influencing caregiving decisions; (2) Evolving challenges related to dementia caregiving; (3) Caregiving burdens/negative impacts from caregiving (relationship burdens and emotional distress); and (4) Coping with their situation in their own ways (cognitive, behavioral, and social strategies).Conclusion: Cultural values (e.g. familism or filial piety) played a significant role in caregiving decisions and experiences. There was a need to raise public awareness of dementia and create culturally and linguistically appropriate training programs for this population.

Sinonasal Organizing Hematoma: Demographics, Diagnosis, and Treatment Outcomes of 112 patients.

INTRODUCTION: Sinonasal organizing hematoma (OH) is a rare, nonneoplastic lesion that often presents with epistaxis, a reddish mass, and destruction of the involved sinonasal structures. Due to its rarity, the demographics, diagnostic modalities, treatment strategies, and outcomes have not yet been studied in a large, long-term study. MATERIALS AND METHODS: Retrospect cohort of 112 sinonasal OH patients treated between 1997 and 2020 in a tertiary, university hospital were evaluated. Demographics, systemic comorbidities, sinonasal surgery history, serum laboratory tests, radiological findings, and treatment results were collected. The present study aimed to assess the accuracy of preoperative computed tomography (CT), Gadolinum-enhanced magnetic resonance (MR), and punch biopsies in detecting sinonasal OH as the most likely diagnosis. In addition, incidental differences by age and year of diagnosis were calculated using the Poisson log-linear regression model. RESULTS: The median age was 44, and 58% were male. Fewer than 20% of these cases had a chronic systemic comorbidity, bleeding tendency, or sinonasal surgery history. MR had the highest accuracy of (87%) to detect sinonasal OH as the most likely diagnosis, compared with contrast-enhanced-CT (53%), punch biopsy (49%), and non-enhanced-CT (16%) (all <0.05). Sinonasal OH incidence did not vary by age, but the yearly rate significantly increased by 1.05 times over 23 years (p < 0.05). Notably, 84% of 112 patients received surgical removal through the assistance of an endoscope, and none had substantial bleeding without preoperative embolization. CONCLUSION: Sinonasal OH was observed regardless of age, sex, systemic comorbidities, bleeding tendency, prior sinonasal surgery, or trauma. Preoperative MR gives the highest accuracy for detecting this disease. Sinonasal OH may be safely managed with endoscopic-assisted surgery removal without embolization. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1581-1590, 2024.

Computational modeling approaches for developing a synergistic effect prediction model of estrogen agonistic activity.

The concerns regarding the potential health threats caused by estrogenic endocrine-disrupting chemicals (EDCs) and their mixtures manufactured by the chemical industry are increasing worldwide. Conventional experimental tests for understanding the estrogenic activity of mixtures are expensive and time-consuming. Although non-testing methods using computational modeling approaches have been developed to reduce the number of traditional tests, they are unsuitable for predicting synergistic effects because current prediction models consider only a single chemical. Thus, the development of predictive models is essential for predicting the mixture toxicity, including chemical interactions. However, selecting suitable computational modeling approaches to develop a high-performance prediction model requires considerable time and effort. In this study, we provide a suitable computational approach to develop a predictive model for the synergistic effects of estrogenic activity. We collected datasets on mixture toxicity based on the synergistic effect of estrogen agonistic activity in binary mixtures. Using the model deviation ratio approach, we classified the labels of the binary mixtures as synergistic or non-synergistic effects. We assessed five molecular descriptors, four machine learning-based algorithms, and a deep learning-based algorithm to provide a suitable computational modeling approach. Compared with other modeling approaches, the prediction model using the deep learning-based algorithm and chemical-protein network descriptors exhibited the best performance in predicting the synergistic effects. In conclusion, we developed a new high-performance binary classification model using a deep neural network and chemical-protein network-based descriptors. The developed model will be helpful for the preliminary screening of the synergistic effects of binary mixtures during the development process of chemical products.

Pyrogenic Black Carbon Suppresses Microbial Methane Production by Serving as a Terminal Electron Acceptor.

Methane (CH4) is the second most important greenhouse gas, 27 times as potent as CO2 and responsible for >30% of the current anthropogenic warming. Globally, more than half of CH4 is produced microbially through methanogenesis. Pyrogenic black carbon possesses a considerable electron storage capacity (ESC) and can be an electron donor or acceptor for abiotic and microbial redox transformation. Using wood-derived biochar as a model black carbon, we demonstrated that air-oxidized black carbon served as an electron acceptor to support anaerobic oxidation of organic substrates, thereby suppressing CH4 production. Black carbon-respiring bacteria were immediately active and outcompeted methanogens. Significant CH4 did not form until the bioavailable electron-accepting capacity of the biochar was exhausted. An experiment with labeled acetate (13CH3COO-) yielded 1:1 13CH4 and 12CO2 without biochar and predominantly 13CO2 with biochar, indicating that biochar enabled anaerobic acetate oxidation at the expense of methanogenesis. Methanogens were enriched following acetate fermentation but only in the absence of biochar. The electron balance shows that approximately half (∼2.4 mmol/g) of biochar's ESC was utilized by the culture, corresponding to the portion of the ESC > +0.173 V (vs SHE). These results provide a mechanistic basis for quantifying the climate impact of black carbon and developing ESC-based applications to reduce CH4 emissions from biogenic sources.

SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVID-19.

IMPORTANCE: Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.

Association between antibiotics and asthma risk among adults aged over 40 years: a nationally representative retrospective cohort study.

INTRODUCTION: Several studies have reported that exposure to antibiotics can lead to asthma during early childhood. However, the association between antibiotic use and risk of asthma in the adult population remains unclear. This study aimed to investigate the association between antibiotic use and asthma in adults. METHODS: We used data from the National Health Insurance Service (NHIS)-Health Screening Cohort, which included participants aged ≥40 years who had health screening examination data in 2005-2006. A total of 248 961 participants with a mean age of 55.43 years were enrolled in this retrospective cohort study. To evaluate antibiotic exposure from the NHIS database for 5 years (2002-2006), cumulative usage and multiclass prescriptions were identified, respectively. During the follow-up period (2007-2019), 42 452 patients were diagnosed with asthma. A multivariate Cox proportional hazard regression model was used to assess the association between antibiotic use and newly diagnosed asthma. RESULTS: Participants with antibiotic use for ≥91 days showed a higher risk of asthma (adjusted HR (aHR) 1.84, 95% CI 1.72 to 1.96) compared with participants who did not use antibiotics (n=38 450), with a duration-dependent association (ptrend<0.001). Furthermore, ≥4 antibiotic class user group had an increased risk of asthma (aHR 1.44, 95% CI 1.39 to 1.49) compared with one class of antibiotic use (n=64 698). Also, one class of antibiotic use had a higher risk of asthma (aHR 1.21, 95% CI 1.17 to 1.26) compared with non-users, and it also showed a duration-dependent relationship in all classes, including 1, 2, 3 and ≥4 class group (ptrend<0.001). The duration-response relationship between antibiotic use and increased risk of asthma remained in our sensitivity analyses with the washout and shifting of the index date. CONCLUSIONS: The duration-response pattern observed in antibiotic use and asthma may suggest the implication of proper antibiotic use and management in adults.

The arousal effect of sugammadex reversal of neuromuscular blockade differs with anesthetic depth in propofol-remifentanil anesthesia: a randomized controlled trial.

Sugammadex reverses neuromuscular blockade by encapsulating steroidal neuromuscular blockers; therefore, it does not pharmacologically affect sedation levels. However, some clinicians avoid using it because of sudden unwanted acting out or patient arousal. Previous studies suggested sugammadex-induced awakening, but frontal muscle contraction after sugammadex administration compromised reliability of results obtained from EEG-based anesthesia depth monitoring tools like bispectral index (BIS). We hypothesized that sugammadex would affect patients' arousal depending on their baseline levels of sedation. We evaluated arousal signs after sugammadex administration with BIS between 25 - 35 and 45 - 55 under steady-state propofol-remifentanil anesthesia at the end of a surgery (n = 33 in each group). After sugammadex administration, twelve patients with a BIS of 45 - 55 showed clinical signs of awakening but none with a BIS of 25 - 35 (36.4% vs. 0%, P = 0.001). The distribution of the modified observer's assessment of alertness/sedation scale scores was also significantly different between the two groups (P < 0.001). Changes in the BIS were significantly greater in the BIS 45 - 55 than in the 25 - 35 group (median difference, 7; 95% CI 2 - 19, P = 0.002). Arousal after sugammadex was affected by patient sedation levels, and clinical signs of awakening appeared only in those with BIS 45 - 55. Unwanted arousal of the patient should be considered when using sugammadex under shallow anesthesia.Clinical trial registry number: Clinical Trial Registry of Korea ( https://cris.nih.go.kr ; Principal investigator: Jieae Kim; Registration number: KCT0006248; Date of first registration: 11/06/2021).

Design of siRNA Bioconjugates for Efficient Control of Cancer-Associated Membrane Receptors.

Research on siRNA delivery has seen tremendous growth over the past few decades. As one of the major delivery strategies, siRNA bioconjugates offer the potential to enhance and extend the pharmacological properties of siRNAs while minimizing toxicity. In this paper, we suggest the development of a siRNA conjugate platform with peptides and proteins that are ligands of target receptors for cancer treatment. The siRNA bioconjugates target and block the receptor membrane proteins, enter the cells through receptor-mediated endocytosis, and inhibit the expression of that same target membrane receptor, thereby doubly controlling the function of the membrane proteins. The three kinds of bioconjugates targeting CD47, PD-L1, and EGFR were synthesized via two different copper-free click chemistry reactions. Results showed the cellular uptake of each conjugate, reduction of target gene expression, and efficient functional control of receptor proteins. This platform provides an effective approach for regulating membrane proteins in various diseases beyond cancer.

Scalable, flexible carbon fiber electrode thread arrays for three-dimensional probing of neurochemical activity in deep brain structures of rodents.

We developed a flexible "electrode-thread" array for recording dopamine neurochemicals from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin (∼10 µm diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single-entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility. This spatial redistribution allows navigation of the CFETs towards deep brain targets spreading horizontally from the axis of insertion. Commercial "linear" arrays provide single-entry insertion but only allow measurements along the axis of insertion. Horizontally configured arrays inflict separate penetrations for each individual channel. We tested functional performance of our CFET arrays in vivo for recording dopamine and for providing lateral spread to multiple distributed sites in the rat striatum. Spatial spread was further characterized in agar brain phantoms as a function of insertion depth. We also developed protocols to slice the embedded CFETs within fixed brain tissue using standard histology. This method allowed extraction of the precise spatial coordinates of the implanted CFETs and their recording sites as integrated with immunohistochemical staining for surrounding anatomical, cytological, and protein expression labels. Our CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson's disease and major mood disorders.

Body distribution and ecotoxicological effect of nanoplastics in freshwater fish, Zacco platypus.

The increased consumption of plastics worldwide, has led to the emergence of nanoplastics as important environmental pollutants. Despite the presence of nanoplastics in aquatic environments, their effects on ecosystems remain largely unexplored due to the analysis complexity. This study investigated the organ accumulation and toxic effects of 50 nm polystyrene nanoplastics (PS-NPs) in Zacco platypus (Z. platypus; also known as pale chub fish) using pyrolyzer-gas chromatography-mass spectrometry (Pyr-GC/MS). PS-NPs accumulated in Z. platypus' brain, digestive tract, branchia, and liver, causing changes at cellular level. Over a 14-day exposure, the accumulated PS-NPs led to observable changes in fish behavior (e.g., Total traveled distance and maximum velocity). In addition, the oxidative stress in each organ of Z. platypus increased as the exposure concentration of PS-NPs increased. This study shows that accumulation of nanoplastics in fish, resulting in behavioral changes and biochemical toxicity. As the pattern of change magnifies with exposure time and concentration, from a long-term perspective, the influence of nanoplastics on aquatic ecosystems become evident. This underscores the urgency for continuous research into the potential risks of nanoplastics in aquatic ecosystems.

Icariin Supplementation Suppresses the Markers of Ferroptosis and Attenuates the Progression of Nonalcoholic Steatohepatitis in Mice Fed a Methionine Choline-Deficient Diet.

Icariin, a flavonoid abundant in the herb Epimedium, exhibits anti-ferroptotic activity. However, its impact on nonalcoholic steatohepatitis (NASH) development remains unclear. This study aimed to investigate the potential role of icariin in mitigating methionine choline-deficient (MCD) diet-induced NASH in C57BL/6J mice. The results showed that icariin treatment significantly reduced serum alanine aminotrasferase and aspartate aminotransferase activities while improving steatosis, inflammation, ballooning, and fibrosis in the liver tissues of mice fed the MCD diet. These improvements were accompanied by a substantial reduction in the hepatic iron contents and levels of malondialdehyde and 4-hydroxynonenal, as well as an increase in the activities of catalase and superoxide dismutase. Notably, icariin treatment suppressed the hepatic protein levels of ferroptosis markers such as acyl-CoA synthetase long-chain family member 4 and arachidonate 12-lipoxygenase, which were induced by the MCD diet. Furthermore, transmission electron microscopy confirmed the restoration of morphological changes in the mitochondria, a hallmark characteristic of ferroptosis, by icariin. Additionally, icariin treatment significantly increased the protein levels of Nrf2, a cystine/glutamate transporter (xCT), and glutathione peroxidase 4 (GPX4). In conclusion, our study suggests that icariin has the potential to attenuate NASH, possibly by suppressing ferroptosis via the Nrf2-xCT/GPX4 pathway.