Zeolitic imidazolate framework-8 nanoparticles (ZIF-8), a multifunctional metal-organic framework material with broad application prospects, have attracted increasing attention because of their potential environmental risks. However, their toxicity to terrestrial organisms remains poorly understood. Here, we evaluated the acute toxicity of ZIF-8 to the earthworm Eisenia fetida and compared the toxicological effects of different formulations in a terrestrial exposure system. Following OECD guidelines, a 14-day soil exposure study demonstrated that ZIF-8 exhibited acute toxicity, with the methanol-dispersed formulation showing the lowest LC50 (48.034 mg/kg; median overall survival, OS: 5 days), followed by the dry powder (LC50: 171.730 mg/kg; OS: >12 days) and the aqueous-dispersed formulation (LC50: 240.454 mg/kg; OS: 6 days). Growth inhibition, abnormal behaviors, and surface lesions were observed in all exposure groups, accompanied by reproductive epithelial atrophy, reduced secretory function, and histopathological damage. Ultrastructural examination further revealed mitochondrial swelling, cristae disruption, and numerous electron-dense particle-like structures within the cytoplasm of reproductive epithelial cells. Although these intracellular structures exhibited sizes comparable to those of the synthesized ZIF-8 nanoparticles, their identity could not be definitively confirmed. Overall, our findings indicate that mitochondrial alterations are associated with ZIF-8-induced reproductive injury and may contribute to reproductive epithelial damage. These results provide new evidence for formulation-dependent toxicity of ZIF-8 and contribute to the environmental risk assessment of metal-organic framework nanomaterials in terrestrial ecosystems.

Hepatitis E virus (HEV) is increasingly recognized as a cause of neurological disease beyond its hepatic manifestations. Neurological complications are the most frequently reported extrahepatic presentations and include both peripheral nervous system disorders, such as Guillain–Barré syndrome (GBS) and neuralgic amyotrophy (NA), and central nervous system (CNS) involvement, including encephalitis and myelitis, often in the absence of overt hepatitis. This review summarizes the clinical spectrum of HEV-associated neurological disease and integrates evidence from human studies and experimental models. Current evidence supports multifactorial pathogenesis, with direct viral neuroinvasion of the CNS and immune-mediated mechanisms predominating in peripheral neuropathies. Experimental in vivo and in vitro systems demonstrate that HEV can cross the blood–brain barrier (BBB) and replicate within neural tissues, providing biological plausibility for CNS involvement. By synthesizing clinical and experimental findings, this review highlights the dual pathogenic pathways underlying HEV-associated neurological injury and outlines key unresolved questions relevant to diagnosis, pathogenesis, and clinical management.

Hepatitis E virus (HEV) is a zoonotic pathogen that can infect pregnant women and cause adverse pregnancy outcomes, including miscarriage and preterm delivery. The previous study demonstrated that HEV genotype 3 (HEV-3) inhibits complete autophagic flux in both mouse placental tissue and human trophoblast cells (JEG-3), evidenced by reduced expression of ATG proteins (including LC3, Beclin1, ATG4B, ATG5, and ATG9A) and accumulation of p62. However, the specific regulatory pathway involved remains unclear. Thus, eukaryotic expression vectors for HEV open reading frames (ORFs) were constructed, and ORF2 and ORF3 proteins were transiently overexpressed in JEG-3 cells via liposome transfection. While both ORF2 and ORF3 significantly reduced LC3B protein levels (p < 0.01), only ORF2 induced p62 accumulation (p < 0.01), indicative of autophagic inhibition, which indicates that ORF2 was the key viral protein mediating autophagy suppression in JEG-3. The results of WB and RT-qPCR showed that ORF2 suppressed the PI3K/Akt/mTOR pathway while enhancing nuclear translocation of TFEB (p < 0.01) and AMPK phosphorylation (p < 0.01), suggesting paradoxical activation of upstream autophagy regulators. Through co-transfection of mCherry-LC3 with ORF2, co-localization studies, and AlphaFold 3-based intermolecular interaction predictions, we propose that ORF2 directly binds LC3B to block autophagosome formation. Finally, co-immunoprecipitation confirmed physical interaction between HEV ORF2 and LC3B, elucidating the molecular mechanism of HEV-induced autophagy suppression in trophoblasts. These findings reveal the molecular mechanism by which HEV inhibits autophagy leading to miscarriage in mice, providing new insights into HEV-induced reproductive damage.

Abstract Norovirus (NoV) is a leading cause of acute gastroenteritis worldwide. Irrigation water has been confirmed as a vector for transmitting NoV to crops. The study aimed to analyze the prevalence of NoV in irrigation water across China and assess its implications for food safety. Between December 2023 and April 2024, 200 irrigation water samples were collected from 27 cities. Viral concentration was performed using tangential flow filtration, followed by RNA extraction and RT-qPCR detection for NoV genogroups GI and GII. NoV was detected in 17 samples (8.50%, 17/200). Among the positive samples, GI was identified in 8 (4.00%), GII in 14 (7.00%), with 5 samples (2.50%) positive for both genogroups. The results indicated that the detection rate of NoV in irrigation water exhibited seasonal variation, with a significantly higher rate observed in winter compared to spring (p < 0.001). Irrigation water in China is a reservoir for NoV, with a significantly higher contamination level in winter. These findings highlight irrigation water as a potential risk factor for foodborne and waterborne NoV transmission and warrant focused attention in public health strategies.

Introduction: Bacterial biofilms are a major cause of persistent and device-related infections due to their antibiotic resistance and ability to shelter bacteria. Zinc oxide nanocrystals (ZnO NCs), with their multiple antimicrobial mechanisms, have emerged as efficient antibacterial agents. Methods: In this study, we synthesized rod-shaped ZnO NCs and evaluated their anti-biofilm efficacy against Escherichia coli. Antibiofilm activity was assessed at sub-minimum inhibitory concentration (MIC) and MIC levels. Transcriptomic analysis and qPCR were employed to examine gene expression changes in E. coli, with further mechanistic validation targeting specific metabolic pathways. Results: At sub-MIC levels, ZnO NCs potently inhibited biofilm formation and eradicated pre-formed E. coli biofilms. These treatments also markedly suppressed the synthesis of key extracellular polymeric substances (EPS) components, while MIC-level treatments effectively degraded existing EPS in mature biofilms. Concurrently, ZnO NCs reduced overall EPS density, loosened biofilm architecture, and increased its structural heterogeneity. Furthermore, bacterial motility (swimming, twitching, and swarming) was strongly impaired across sub-MIC to MIC concentrations. Transcriptomic analysis revealed that ZnO NCs downregulated genes associated with biofilm formation, motility, and amino acid biosynthesis. qPCR indicated that the downregulation of glgA and gltB impaired the synthesis of key EPS components. Conclusion: Mechanistically, we validate that in E. coli, ZnO NCs suppress glgA to disrupt glycogen-derived carbon precursors for polysaccharide synthesis, and downregulate gltB to impair glutamate synthase activity, thereby limiting nitrogen assimilation and amino acid supply for proteinaceous EPS components. These findings elucidate a previously undefined mechanism wherein ZnO NCs dismantle E. coli biofilms by simultaneously targeting two pivotal metabolic nodes (glgA and gltB) that fuel EPS production. This work provides not only a deeper mechanistic insight into anti-biofilm action against E. coli but also supports the potential of ZnO NCs as multi-targeted anti-biofilm agents.

Microplastics, defined as plastic fragments smaller than 5 mm, degrade from larger pollutants, with nanoscale microplastic particles presenting significant biological interactions. This study investigates the toxic effects of polystyrene nanoplastics (PS-NPs) on juvenile mice, which were exposed through lactation milk and drinking water at concentrations of 0.01 mg/mL, 0.1 mg/mL, and 1 mg/mL. The results show that PS-NP exposure during lactation and juvenile periods caused delayed weight gain and impaired organ development, particularly in the liver and kidneys, without causing functional abnormalities or toxic injuries. The primary toxicity of PS-NPs was observed in the intestinal tract, including shortened villi, disrupted tight junctions, inhibited epithelial cell proliferation, and oxidative stress responses. These findings highlight the importance of evaluating the developmental toxicity of nanoplastics at environmentally relevant doses.

IntroductionConventional approaches to treat ulcerative colitis (UC) focus on suppressing excessive inflammation and immune responses. Nevertheless, these treatments fail to address gut dysbiosis or restore the intestinal mucosal barrier effectively. Regulating the intestinal microenvironment may be pivotal to more effective therapies for UC.MethodsHerein, oral colon-targeted microspheres, sodium alginate-chitosan-encapsulate quercetin (SA-Q-CS MPs), were developed. The stability and pH responsiveness of SA-Q-CS MPs were explored. Therapeutic effects were assessed in dextran sulfate sodium (DSS)-induced ulcerative colitis in female C57BL/6 mice via 16S ribosomal RNA (rRNA) gene sequencing, Disease Activity Index (DAI) scoring, colonic histopathology, inflammatory and antioxidant levels, and intestinal barrier function.Results and DiscussionSA-Q-CS MPs markedly enhanced the overall richness and diversity of the gut microbiota, enhancing the abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroidales, Lactobacillales, and Lachnospiraceae. These changes contributed to improved intestinal barrier function, better metabolic processes, and stronger defense mechanisms, thereby ameliorating UC induced by 3% dextran sulfate sodium (DSS) in C57BL/6J mice. Compared to the DSS group, the SA-Q-CS MPs treatment group showed significant improvements, with the Disease Activity Index (DAI) and histopathological scores reduced by more than 66.9%, pro-inflammatory factor levels decreased by 65%, antioxidant levels increased over sevenfold, and tight junction protein expression elevated by more than threefold. In conclusion, this investigation presents SA-Q-CS MPs as a promising strategy for restoring gut microbiome homeostasis and providing precise treatment for UC.

This study quantitatively assessed microplastic contamination in commercial chicken eggs and hen ovarian follicles. Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS) and Laser Direct Infrared Analysis (LDIR) analyses revealed universal microplastic contamination. The dominant polymers-polypropylene, polyethylene, and polystyrene-reached concentrations of up to 227 μg/g, averaging 17.0 μg/g per egg. Crucially, maternal transfer was confirmed, with polystyrene and polyethylene detected in all ovarian follicles (6/6) at mean concentrations of 8.1 and 61.0 μg/g, respectively. To evaluate toxicity, polystyrene nanoplastics were injected into yolk sacs at 0.2, 1.0, and 5.0 mg/egg, a range where the medium dose modeled detected levels while low and high doses established dose-response relationships. Exposure caused dose-dependent growth retardation (14-day body weight: 75.4 g vs. 91.6 g in controls) and intestinal villus atrophy (556 μm vs. 787 μm). Mechanistically, transcriptomics identified disrupted autophagic flux and epithelial junctions as key toxicity pathways. This study emphasizes the potential health risks of dietary microplastic exposure.

ABSTRACT Hepatitis E virus (HEV) is a globally prevalent zoonotic pathogen that is primarily spread through the fecal-oral route, such as by consuming undercooked or contaminated pork. HEV infection leads to an estimated 3.3 million symptomatic cases of viral hepatitis and 70,000 deaths in human populations each year. Therefore, a rapid and accurate method for detecting HEV in serum or stool samples is essential. In this study, we aimed to develop and evaluate two methods for the rapid and convenient detection of HEV RNA: reverse transcription recombinase-aided amplification with lateral flow dipstick (RT-RAA-LFD) and quantitative real-time reverse transcription recombinase-aided amplification (qRT-RAA). We optimized the reaction conditions and assessed their sensitivity and specificity. The RT-RAA-LFD assay completed its reaction at 39°C within 15 minutes, achieving a 95% limit of detection (LOD) of 247 copies/μL. The qRT-RAA assay, completed at 42°C within 20 minutes, had a 95% LOD of 25 copies/μL. Both assays demonstrated no cross-reactivity with other porcine pathogens and exhibited strong specificity. In testing 245 porcine bile and fecal samples, the RT-RAA-LFD assay showed a kappa value of 0.943 ( P < 0.001) with a 97.14% (238/245) coincidence rate compared with quantitative reverse transcription PCR. Similarly, the qRT-RAA assay achieved a kappa value of 0.976 ( P < 0.001) with a 98.78% (242/245) coincidence rate. In conclusion, these two RT-RAA assays show promising potential as effective diagnostic tools for broad and efficient screening of swine HEV in veterinary clinics. IMPORTANCE Hepatitis E virus (HEV) is a globally widespread zoonotic pathogen that poses a significant public health risk. Swine serve as the primary natural host for zoonotic HEV. This study introduces a rapid and precise method for detecting swine HEV RNA, showcasing its potential as an effective diagnostic tool for comprehensive and efficient screening of swine HEV in veterinary clinics.

In recent years,the global incidence of hepatitis E virus(HEV)has been rising,leading to increased morbidity and mortality associated with hepatitis.Cas13,a CRISPR effector,shows promise as an antiviral agent against single-stranded RNA viruses.Cas13d,a type Ⅵ-D effector,exhibits higher efficiency in suppressing RNA viruses compared to other type Ⅵ variants.

Polystyrene nanoparticles are emerging as contaminants in freshwater environments, posing potential risks to amphibians exposed to extended periods of water contamination. Using tadpoles as a model, this study aimed to evaluate the toxicity of PS NPs. Pyrolysis-gas chromatography-tandem mass spectrometry (Py-GCMS) analysis revealed a concentration-dependent increase in polystyrene nanoparticles (PS NPs) levels in tadpoles with escalating exposure concentrations. Following exposure to 100 nm fluorescent microspheres, fluorescence was observed in the intestines and gills, peaking at 48 hours. Histopathological analysis identified degenerative necrosis and inflammation in the liver, along with atrophic necrosis of glomeruli and tubules in the kidneys. These results indicate a discernible impact of PS NPs on antioxidant levels, including reduced superoxide dismutase and catalase activities, elevated glutathione content, and increased malondialdehyde levels. Electron microscopy observations revealed the infiltration of PS NPs into Kupffer's cells and hepatocytes, leading to visible lesions such as nuclear condensation and mitochondrial disruption. The primary objective of this research was to elucidate the adverse effects of prolonged PS NPs exposure on amphibians.

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long -term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed. Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs. Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 mu g/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 mu g/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (center dot OH) compared to ZnO NPs. Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.

IntroductionThe frequent occurrence of mutations in the SARS-CoV-2 Spike (S) protein, with up to dozens of mutations, poses a severe threat to the current efficacy of authorized COVID-19 vaccines. Membrane (M) protein, which is the most abundant viral structural protein, exhibits a high level of amino acid sequence conservation. M protein ectodomain could be recognized by specific antibodies; however, the extent to which it is immunogenic and provides protection remains unclear.MethodsWe designed and synthesized multiple peptides derived from coronavirus M protein ectodomains, and determined the secondary structure of specific peptides using circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect IgG responses against the synthesized peptides in clinical samples. To evaluate the immunogenicity of peptide vaccines, BALB/c mice were intraperitoneally immunized with peptide-keyhole limpet hemocyanin (KLH) conjugates adjuvanted with incomplete Freund’s adjuvant (IFA). The humoral and T-cell immune responses induced by peptide-KLH conjugates were assessed using ELISA and ELISpot assays, respectively. The efficacy of the S2M2-30-KLH vaccine against SARS-CoV-2 variants was evaluated in vivo using the K18-hACE2 transgenic mouse model. The inhibitory effect of mouse immune serum on SARS-CoV-2 virus replication in vitro was evaluated using microneutralization assays. The subcellular localization of the M protein was evaluated using an immunofluorescent staining method, and the Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) activity of the S2M2-30-specific monoclonal antibody (mAb) was measured using an ADCC reporter assay.ResultsSeroconversion rates for ectodomain-specific IgG were observed to be high in both SARS-CoV-2 convalescent patients and individuals immunized with inactivated vaccines. To assess the protective efficacy of the M protein ectodomain-based vaccine, we initially identified a highly immunogenic peptide derived from this ectodomain, named S2M2-30. The mouse serum specific to S2M2-30 showed inhibitory effects on the replication of SARS-CoV-2 variants in vitro. Immunizations of K18-hACE2-transgenic mice with the S2M2-30-keyhole limpet hemocyanin (KLH) vaccine significantly reduced the lung viral load caused by B.1.1.7/Alpha (UK) infection. Further mechanism investigations reveal that serum neutralizing activity, specific T-cell response and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) correlate with the specific immuno-protection conferred by S2M2-30.DiscussionThe findings of this study suggest that the antibody responses against M protein ectodomain in the population most likely exert a beneficial effect on preventing various SARS-CoV-2 infections.

AIMS:To develop and evaluate nisin-loaded chitosan/sodium alginate (CS/SA) microspheres as an improved antimicrobial delivery system targeting Staphylococcus aureus strains. METHODS AND RESULTS:The microspheres were prepared using a modified water-in-oil emulsion cross-linking method, resulting in spherical particles sized 1-8 µm with a surface charge of -7.92 ± 5.09 mV, confirmed by scanning electron microscopy (SEM) and Zetasizer analysis. Encapsulation efficiency (EE) and loading capacity (LC) of nisin were 87.60% ± 0.43% and 1.99% ± 0.01%, respectively. In vitro release studies over 48 h indicated a controlled release pattern of nisin, described by the Korsmeyer-Peppas model, with higher release rates at 37°C and alkaline pH. Antimicrobial assays showed an enhanced efficacy of nisin-loaded CS/SA microspheres compared to free nisin, with minimum inhibitory concentration values reduced by 50%. Confocal laser scanning microscopy (CLSM), SEM, and transmission electron microscopy showed significant bacterial membrane damage and cellular disruption induced by the microspheres. CONCLUSIONS:This study highlights the potential of nisin-loaded CS/SA microspheres as an innovative antimicrobial delivery system with improved stability and antimicrobial efficacy against S. aureus, addressing limitations associated with nisin applied alone.

Background:A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT). Materials and Methods:In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy. Results:MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response. Conclusion:The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.

AbstractThe Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 μg mL−1 and 60 mg kg−1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine. Graphical Abstract

AbstractNanomaterials, including ZIF‐8 nanoparticles (NPs), are shown to be effective antimicrobial agents against Methicillin‐resistant Staphylococcus aureus(MRSA). However, the antibiofilm properties and mechanisms of ZIF‐8 NPs remain uncertain. In this study, ZIF‐8 NPs are prepared using the room temperature solution reaction method and characterized. Biofilm formation inhibition test and biofilm eradication test are performed and the results show that ZIF‐8 NPs can inhibit the formation of MRSA biofilm as well as disperse established MRSA biofilm. Proteomics and real‐time fluorescence quantitative polymerase chain reaction (PCR) are conducted to prove that ZIF‐8 NPs reduce the expression of adhesion‐related proteins, namely the fibronectin‐binding proteins A and B (fnbA/fnbB), fibrinogen binding protein caking factors A and B (clfA/clfB), elastin binding protein (ebps), and fibrin binding protein (eno). ZIF‐8 NPs also inhibit the arginine biosynthesis pathway by affecting the activities of argininosuccinate lyase, ornithine carbamyl transferase, Glutamate dehydrogenase, carbamate kinase, and arginine deiminase. A conclusion can be drawn from the above results that ZIF‐8 NPs can inhibit bacterial adhesion and kill bacteria directly, ultimately destroying MRSA biofilm. This study provides a molecular basis for the treatment of MRSA biofilm with ZIF‐8 NPs.

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In this study, we propose a novel therapy system composed of UiO-66 nanoparticles, which contain quercetin combined with chloroquine (UQCNP), to achieve dual autophagy-ubiquitination blockade. Through UiO-66 NP drug loading, the solubility of quercetin (a proteasome inhibitor) was improved under physiological conditions, thereby increasing its effective concentration at the tumor site. The cell experiment results showed that UQCNP significantly increased the apoptosis rate of 4T1 cells by 73.6%, which was significantly higher than other groups. Transmission electron microscopy results showed that the autophagosome of cells in the UQCNP treatment group was significantly lower than that in other treatment groups. Moreover, western blot results showed that, compared with other groups, LC3 expression and proteasome activity (p < 0.01), as well as the tumor volume of mice treated with UQCNP (p < 0.01) were significantly reduced. These results indicate that UQCNP achieves effective tumor therapy by blocking the autophagy and proteasome pathways synchronously.

The persistent detection of nano-sized plastic particles in humans, animals, and animal-derived products underscores the potential impact of these particles on living organisms. Consequently, the toxicology of such particles has emerged as a pivotal research interests in recent years. In this study, NP was synthesized successfully with an average particle size of 100 nm using a emulsion polymerization method as model particles. Following co-incubation of IEC-6 cells with NP for 24-168 h, a notable inhibition of cell viability and proliferation was observed. The significant activation of autophagy and a concomitant blockage of autophagic flux in IEC-6 cells after 24-72 h of co-incubation with NP were unveiled by transmission electron microscopy, western blotting, and double-fluorescent autophagy analysis. A significant increase in the number of lysosomes and an increase in the expression of hydrolase CTSB were detected, indicating dysregulation of lysosomal function. The subsequent transcriptomic and metabolomics analyses, coupled with the observation of activated lysosomes and the RIPK1-RIPK3-MLKL/PYGL pathway, led us to posit that the blockade of autophagy and lysosomal dysfunction, culminating in lysosomal membrane permeabilization (LMP) induced necroptosis, constitutes one of the mechanisms contributing to the cytotoxicity of NP. SYNOPSIS: The cytotoxicity and its related mechanisms of nano-plastic is still unclear. This study found that nano-plastics may induce necroptosis in cells, and autophagy blockade and lysosomal dysfunction are prodromal manifestations.