BACKGROUND: Liver injury is a frequent complication of heatstroke and constitutes a direct cause of death. However, only a few studies examined the mechanism underlying heatstroke-induced liver injury. OBJECTIVE: We aimed to evaluate the role of peroxisome proliferator-activated receptor α (PPARα) in heatstroke-induced liver injury and to explore the potential mechanisms. METHODS: Male C57BL/6N mice were subjected to a control (22 ± 1 °C) or extreme heat temperature (39.5 ± 0.5 °C) to induce a heatstroke-associated liver injury animal model. PPARα agonist, ferroptosis inhibitor, and AAV8-mediated PPARα overexpression were administered to the mice to investigate the role of PPARα and ferroptosis in the heatstroke-induced liver injury. Serum was collected for liver function evaluation. Liver tissues were applied for morphological observation, staining detection, ferroptosis examination, and mechanistic exploration. RESULTS: Compared with the control group, extreme heat exposure-induced temperature dysregulation, impaired liver function, and morphological damage in mice. Proteomics screened PPARα as a protein of interest, with its level being significantly decreased in response to extreme heat exposure. Both PPARα activation and overexpression attenuated extreme heat-induced heatstroke and liver injury. Hmox1 was next screened and higher Hmox1 expression was identified, accompanied by elevated markers of ferroptosis including prostaglandin-endoperoxide synthase 2 (Ptgs2), malondialdehyde (MDA), lipid peroxidation (LPO) and Fe2+ levels. Ferroptosis inhibition mitigated heatstroke and liver injury induced by heat exposure. In the setting of extreme heat exposure, PPARα activation suppressed Hmox1 expression and the levels of ferroptosis markers. It not only induced differences in the expression of members of iron generation, efflux and uptake process and reduced hepatic intracellular Fe2+ accumulation, but also stimulated expression of molecules for countering lipid peroxidation including Nrf2-SLC7A11-GPX4 axis and FSP1 signaling. DISCUSSION: PPARα played an essential role in extreme heat exposure-induced heatstroke and liver injury, and PPARα intervention conferred protection against it via inhibition of ferroptosis.

Nitrogen level significantly impacts rice resistance to the brown planthopper (BPH, Nilaparvata lugens). Yet, the mechanisms underlying nitrogen level-mediated rice BPH resistance remain largely unclear. Here, we found that, relative to medium nitrogen (MN) and high nitrogen (HN) conditions, low nitrogen (LN) suppressed rice growth but enhanced plant resistance to BPH, as evidenced by reduced nymph biomass, decreased phloem ingestion and lower fecundity. Biochemical and transcriptome analyses revealed that compared to MN and HN plants, LN plants exhibited significantly higher basal and/or BPH-induced levels of abscisic acid (ABA) and salicylic acid (SA), cell wall components (lignin, cellulose and hemicellulose), and certain flavonoids but lower levels of phenolamides. Moreover, the relative water content (RWC) and total amino acid concentrations were significantly lower in LN plants compared with those in MN and HN plants. Impairing the signalling pathway mediated by ABA but not SA in rice abolished the basal and/or BPH-induced accumulation of defence compounds (cell wall components and certain flavonoids) in plants and plant resistance to BPH. The results demonstrate that the ABA signalling pathway, together with reduced RWC and total amino acid concentrations in plants caused by LN conditions, plays an important role in regulating the LN-mediated rice resistance to BPH.

The rising prevalence of metabolic diseases represents a global health challenge, among which metabolically unhealthy normal-weight individuals constitute a largely ignored subgroup. Fine particulate matter (PM2.5), which contains substantial nanoscale particulate matter, is a recognized extrinsic environmental trigger of metabolic disorders in both obese and nonobese situations, whereas the loss of plasticity in inguinal white adipose tissue (iWAT) is a critical intrinsic pathological feature of metabolic diseases. However, the long-term metabolic effects of maternal PM2.5 exposure on nonobese offspring, particularly in iWAT plasticity, and underlying cellular mechanisms remain poorly understood. Here, we revealed that maternal PM2.5 exposure induced insulin resistance in middle-aged male mouse offspring and identified iWAT as a susceptible adipose depot with impaired plasticity, which is characterized by adipocyte hypertrophy, inflammation, fibrosis, and metabolic dysfunction. Using single-cell RNA sequencing on iWAT from middle-aged male mouse offspring, we found that maternal PM2.5 exposure altered the fate decisions of adipose-derived stem cells from adipogenesis to fibrosis through increasing CD142+ adipogenesis-regulatory cell expansion and inducing fibrogenesis in DPP4+ adipose stem cells. Mechanistically, maternal PM2.5 exposure induced IgG production from plasma cells, which promoted fibrogenesis in DPP4+ adipose stem cells by activating macrophages. This process was further exacerbated by monocyte- and macrophage-mediated inflammation. Finally, maternal PM2.5 exposure induced endothelial cell heterogeneity shifts and dysfunction, facilitating immune cell recruitment and naïve B cell differentiation into plasma cells, ultimately initiating IgG-triggered plasticity impairment. This study provided insights into the adverse effects of maternal exposure to environmental pollution on the metabolic health of offspring at single-cell resolution.

The Mediator complex serves as a critical bridge linking transcription factors (TFs) to RNA polymerase II during mRNA synthesis. Among its subunits, MED25 plays a pivotal role in jasmonate (JA) signaling by directly interacting with the master TF of the JA pathway. However, the biological functions of MED25 in monocotyledonous plants, particularly its contribution to JA-mediated responses in rice, remain largely unexplored. Here, we mutated OsMED25 in rice using CRISPR/Cas9-based genome editing and evaluated JA-mediated developmental and defense phenotypes in these osmed25 mutants, JA-deficient allene oxide cyclase (osaoc) mutants, and wild-type plants. We found that osmed25 mutants exhibited defective anther dehiscence and open husks but normal spikelet morphology, whereas osaoc displayed severe spikelet developmental defects, including non-dehiscent anthers. Notably, OsMED25 is essential for rice resistance against the brown planthopper (BPH). While osaoc mutants completely lost JA responsiveness, osmed25 mutants displayed only partial impairment of BPH-induced JA-responsive gene expression, accompanied by a selective reduction in the accumulation of defensive specialized metabolites (e.g., phenolamides and volatile terpenes). Furthermore, OsMED25 participates in a feedback loop modulating JA biosynthesis during BPH infestation. Collectively, our study uncovers the role of OsMED25 in regulating a subset of JA-dependent spikelet development and herbivore resistance in rice.

6:2 chlorinated polyfluorinated ether sulfonate (F-53B, also known as 6:2 Cl-PFESA) is a major alternative to perfluorooctane sulfonate (PFOS) and a widespread environmental pollutant with potential public health hazards. However, its nephrotoxic effects and underlying molecular mechanisms remain poorly understood. This study investigated renal injury induced by environmentally relevant concentrations of F-53B and delineated the mechanistic cascade using a mouse model combined with quantitative proteomic and molecular biological approaches. Male C57BL/6 mice were exposed to 0, 4, 40, and 400 μg/L F-53B for 4 weeks. F-53B exposure led to significant renal dysfunction, histopathological damage, elevated renal injury biomarkers, and pronounced oxidative stress in a dose-dependent manner. A proteomic comparison of the 0 μg/L versus 400 μg/L groups identified 276 differentially expressed proteins that were strongly enriched in oxidative phosphorylation, autophagy, and apoptosis pathways, with cytochrome c oxidase subunit 7b (Cox7b) serving as a core downregulated hub molecule. Further validation confirmed that F-53B triggered overt mitochondrial structural damage, impaired respiratory chain complex assembly, aberrant ATP production, and disturbed mitochondrial dynamics. Consequently, excessive autophagy activation and mitochondrial-mediated apoptosis were simultaneously stimulated in renal tissues. Notably, although statistically significant, the alterations induced by F-53B were generally mild in magnitude. Collectively, our findings demonstrate that F-53B induces nephrotoxicity through a sequential pathological cascade. This study provides novel mechanistic insights into F-53B-elicited renal injury and highlights the potential health risks of this emerging per- and polyfluoroalkyl substance (PFAS) alternative.

Plants emit volatile compounds that orchestrate complex ecological interactions, with methylated catabolites of interaction-induced phytohormones being common examples. Salicylic acid (SA) mediates plant antipathogen responses, while its methylated derivative, MeSA, broadly mediates plant-insect interactions without specificity. Here, we identified dimethyl salicylate (DMSA), an unappreciated dimethylated SA catabolite, emitted by rice when attacked by the major destructive pest, the brown planthopper. DMSA biosynthesis requires an O-methyltransferase cascade, BSMT1 (benzoic acid/salicylic acid carboxyl methyltransferase 1)-MSOMT (methyl salicylate O-methyltransferase), which is directly activated by a jasmonate (JA)-responsive MYC2-JAMYB transcriptional cascade. Natural variation in the MSOMT promoter confers its herbivory-induced expression in indica but not japonica cultivars. Functionally, DMSA acts as a specific volatile signal attracting the egg-parasitoid wasps of brown planthoppers (BPHs) without mediating direct resistance, which demonstrably suppresses BPH populations in paddy fields. DMSA is an optimized advance in SA signaling derived plant "alarm calls" with great potential in sustainable rice pest management.

Fine particulate matter (PM 2.5 ) contributes to metabolic dysfunction, but its effects on adipose tissue browning remain unclear. Here, we showed that PM 2.5 exposure inhibited inguinal white adipose tissue (iWAT) browning by downregulating protein targeting to glycogen (PTG), disrupting glycogen homeostasis. PTG overexpression in iWAT restored glycogen metabolism, thermogenesis, and mitochondrial function, reversing PM 2.5 -induced impairment in iWAT browning and metabolic disorders. Mechanistically, PTG negatively regulated vascular endothelial growth factor B (VEGFB), and VEGFB knockdown rescued browning. Activation of β3-adrenergic receptor (ADRB3) mitigated PM 2.5 ’s effects by restoring PTG and normalizing VEGFB, defining the ADRB3-PTG-VEGFB axis as central to PM 2.5 -induced metabolic dysfunction. Our findings identify adipose glycogen metabolism as a target for countering environmental metabolic disruption.

Hosts deploy mechanosensory systems to intercept herbivory threats, yet how plants decode insect-derived mechanical force remains unclear. Here, we demonstrate that PIEZO-type mechanosensitive ion channel component 1 (PIEZO1) serves as a mechanoimmune hub converting whitefly probing into calcium-dependent defense activation. Mechanical force during feeding activates PIEZO1-dependent Ca2+ influx, triggering CBP60g phosphorylation that amplifies both PIEZO1 transcription and salicylic acid (SA) biosynthesis, forming a self-amplifying defense loop. Furthermore, PIEZO1 positively modulates the core jasmonic acid (JA) transcription factor MYC2, broadening immune responses against insects. Strikingly, the whitefly salivary effector Bsp9 targets PIEZO1’s CAP domain, suppressing Ca2+ fluxes and SA/JA-mediated resistance to promote feeding. Notably, PIEZO1 represents a conserved target of salivary effectors from diverse piercing-sucking insect vectors across both plant and human hosts. Our study unveils the molecular mechanisms underlying host perception of and defense against piercing-sucking insects, pointing to novel strategies against both insects and insect-transmitted diseases.

Time-restricted feeding (TRF), a diet-related regimen confining food intake to defined daily windows (usually 6-12 h), potentially preventing and managing various metabolic disorders effectively. Growing evidence demonstrates that exposure to fine particulate matter (PM2.5) induces a phenotype resembling metabolic dysfunction-associated fatty liver disease (MAFLD) and disrupts hepatic glucose homeostasis. However, it remains unknown whether TRF could attenuate dysregulated hepatic glucose - lipid metabolism caused by exposure to PM2.5 and its underlying molecular mechanisms. This study categorized male C57BL/6 N mice into four groups: the filtered air (FA) exposure group, the PM2.5 exposure group, the TRF + FA exposure group, and the TRF + PM2.5 exposure group. The PM2.5 and TRF + PM2.5 groups were exposed to PM2.5 in whole-body PM2.5 exposure chambers, while the remaining groups continued under filtered air. For the TRF + FA and TRF + PM2.5 groups, feeding was restricted to an 8 - hour period during the active phase (ZT16-ZT24). Our findings revealed that PM2.5 exposure induced dyslipidemia, glucose intolerance, and insulin resistance (IR), accompanied by elevated hepatic triglyceride (TG) and total cholesterol (TC) levels. Specifically, PM2.5 disrupted the expression of molecules related to TG, TC and glucose metabolism, and TRF intervention could ameliorate these effects. Furthermore, PM2.5 exposure suppressed insulin receptor substrate (IRS) and AMP-activated protein kinase (AMPK) signaling pathways, which were reactivated by TRF. In summary, we provide the first evidence that TRF counteracts PM2.5-induced insulin resistance and hepatic steatosis, offering a lifestyle strategy against air-pollution-induced pathologies.

As global warming intensifies, heatstroke and complicated liver injury are increasingly becoming the most serious clinical manifestations of heat-related illnesses. However, effective intervention strategies are lacking. This study aims to investigate the protective effect of resveratrol against heatstroke and complicated liver injury and elucidates its molecular mechanism. In this study, a mouse heatstroke model and an AML12 hepatocyte heat exposure model were established. Resveratrol, HSF1 agonist (HSF1A), HSF1 inhibitor (KRIBB11), and HSF1 knockdown were administered in vivo and/or in vitro to investigate the role of HSF1 and validate the core mechanism by which resveratrol protects against liver injury induced by heat exposure. The results showed that resveratrol pretreatment significantly attenuated temperature dysregulation, liver morphology and function induced by heat exposure. Heat exposure upregulated HSF1 expression in both the mouse liver and hepatocytes. HSF1 activation (agonist HSF1A) caused liver injury, lipid deposition and necroptosis typically induced by heat exposure, while HSF1 inhibition and HSF1 knockout reduced these effects. Resveratrol showed the potential to bind to HSF1 and inhibit HSF1 expression in the liver. Moreover, it protected against heat-induced lipid metabolic disorders and necroptosis both in vivo and in vitro, in which necroptosis inhibition did not alter lipid metabolism in hepatocytes. Finally, HSF1 inhibitor (KRIBB11) administration protected against heat stroke and liver injury induced by heat exposure, similar to resveratrol. In conclusion, resveratrol protects against heatstroke and complicated liver injury by HSF1-mediated necroptosis, which might be triggered by lipid metabolic disorders. This study provides an intervention strategy for heatstroke and associated complicated liver injury.

The phytohormone jasmonic acid (JA) regulates diverse aspects of plant growth, development, and defense, yet how a single hormone coordinates such varied outputs remains poorly understood. Central to jasmonate signaling is the biosynthesis and perception of bioactive JA-amino acid conjugates, such as jasmonoyl-L-isoleucine (JA-Ile), which are synthesized by JASMONATE RESISTANT (JAR) enzymes. Three OsJAR genes are present in the monocot crop rice. Here, we systematically dissect their functions using a complete set of CRISPR-Cas9-derived mutants. OsJAR1 and OsJAR2 redundantly maintain basal JA-Ile levels required for normal vegetative growth, whereas OsJAR3 is functionally attenuated due to low expression and weak enzymatic activity. Notably, OsJAR1 specifically mediates herbivore-induced JA-Ile biosynthesis and confers resistance to the major rice pest, the brown planthopper, under both laboratory and field conditions, whereas OsJAR2 is dispensable for defense. The expression of OsJAR1 is directly controlled by the MYC2-bHLH6 transcriptional cascade, forming a positive feedback loop that sustains JA signaling during herbivory. By contrast, OsJAR2, but not OsJAR1, is expressed during early inflorescence differentiation and contributes to JA-Ile accumulation at this stage, ensuring normal spikelet development. These findings reveal that functional specialization of OsJAR enzymes enables rice to precisely tailor JA responses to distinct developmental and environmental cues.

Nicotine, tobacco’s addictive and potent insecticidal alkaloid, has shaped human history, agriculture, and the plants that produce it. However, the enzymatic steps and reaction mechanisms involved in nicotine biosynthesis remain elusive. Here, we reveal that the final coupling reaction is stabilized by glycosylation via a uridine diphosphate (UDP)-glycosyltransferase, reduced and activated by an A622, condensed through a stereoselective intermolecular Mannich-like reaction, sequentially oxidized by a berberine bridge enzyme-like (BBL), and finally deglycosylated by a β-glucosidase to yield nicotine. A 5-component metabolon assembles at vacuolar membranes to channel both nicotine biosynthesis and its transport. We reconstituted this metabolon both in vitro and heterologously in vivo. Abrogating any of these components depletes nicotine accumulations. A multidrug and toxic compound extrusion (MATE) transporter is essential for efficiently engineering nicotine production in heterologous plant species, which confers pest resistance. This work completes the nicotine biosynthesis pathway and provides critical insights into the intermolecular Mannich-like reaction, a fundamental mechanism for scaffold formation in many plant alkaloids.

The rising prevalence of metabolic diseases represents a global health challenge, with metabolically unhealthy normal-weight (MUHNW) individuals remaining largely overlooked. In addition to direct fine particulate matter (PM2.5) inhalation, there is growing recognition that maternal PM2.5 exposure may be a contributing environmental factor for metabolic disorders. However, the mechanisms by which maternal PM2.5 exposure induced metabolic disorders in the offspring remain unknown. Eight-week-old pregnant C57BL/6N mice were exposed to either filtered air (FA) or ambient PM2.5 throughout gestation, from gestational day 0 to 18, using a whole-body inhalation exposure system. Eight-week-old male C57BL/6N mice were treated once daily for three consecutive days with an antibiotic cocktail containing 1 g/L ampicillin, 0.5 g/L neomycin, 0.5 g/L vancomycin, and 1 g/L metronidazole to generate pseudo-germ-free mice. Subsequently, fecal microbiota from maternal PM2.5-exposed three-week-old male mouse offspring (donor) were transplanted to pseudo-germ-free mice (recipient) via oral gavage twice weekly for five weeks. After fecal microbiota transplantation (FMT), fecal samples from donor and recipient mice were collected for full-length 16S rRNA sequencing. Liver tissue from donor mice was analyzed by 5R 16S rRNA sequencing. Maternal PM2.5 exposure induced non-obese insulin resistance in adult male mouse offspring, with the liver identified as a susceptible organ characterized by suppressed AKT phosphorylation. Subsequently, systemic and hepatic insulin resistance were recapitulated in pseudo-germ-free mice, which received gut microbiota from maternal PM2.5-exposed mouse offspring via FMT. Mechanistically, the increased abundance of Helicobacter hepaticus contributed to DNA damage-mediated colonic barrier injury. This impaired colonic barrier facilitated gut-to-liver translocation of bacteria and lipopolysaccharide (LPS), which triggered hepatic inflammation via activation of TLR4 signaling pathway, ultimately leading to insulin resistance. These findings indicated a causal role for gut microbiota dysbiosis in maternal PM2.5 exposure-induced non-obese insulin resistance in the offspring, providing potential insights into the developmental origins of MUHNW from the perspective of maternal exposure to air pollution.

Herbivore attacks or some pathogen infections typically begin with wounding of plant tissues, yet the transcriptional dynamics of wound-induced responses in the monocot rice remain incompletely understood. Here, we conducted a time-series transcriptome analysis of mechanically wounded rice leaves. Temporal expression patterns were observed even in untreated plants, particularly at dusk. To identify differentially expressed genes (DEGs), we compared wounded and unwounded (control) plants at corresponding time points. Jasmonate-related genes, including 18 biosynthetic and 13 catabolic genes, were significantly up-regulated. Consistently, jasmonic acid (JA) and jasmonoyl-L-isoleucine were rapidly accumulated in wounded tissues within 1 h, followed by JA catabolites after 3 h. Weighted gene co-expression network analysis of upregulated DEGs revealed early- and late-responsive gene modules. Early-expressed genes included putative regulators such as transcription factors, kinases, abscisic acid pathway components, and small peptide-coding genes, while late-responsive genes were primarily involved in specialized metabolite biosynthesis (e.g., phenylpropanoids). Targeted metabolomic analysis showed that most phenolamides were highly accumulated in wounded leaves, whereas flavonoid levels were decreased, likely due to altered metabolic flux in the phenylpropanoid pathway. Comparative analysis of leaf folder (LF) larvae- and wound-induced transcriptomes revealed that only 42

Plant defense against herbivores is primarily regulated by the phytohormone jasmonate (JA). At the core, JA signaling is the MYC2 transcription factor (TF) that regulates the expression of an extensive array of defense-related genes. However, the regulatory mechanisms underlying MYC2-mediated herbivore resistance in rice are not fully understood. We employed brown planthopper (BPH) bioassays, transcriptional activation assays, transcriptome profiling, targeted metabolomics and cleavage under targets and tagmentation-sequencing analysis to investigate the biological function and regulatory mechanism of the JAMYB TF. JAMYB is induced by BPH infestation and is transcriptionally regulated by MYC2. Mutations of JAMYB rendered rice plants susceptible to BPH attacks under laboratory and field conditions, indicating that JAMYB positively contributes to BPH resistance. BPH-elicited biosynthesis of phenolamides and volatile compounds was reduced in jamyb mutants compared with wild-type plants. These specialized metabolites, regulated by JAMYB, function as direct and indirect defenses to deter BPH damage or attract parasitoid wasps of BPH eggs. Furthermore, we found that JAMYB directly binds to AC motifs of key phenylpropanoid pathway genes and activates their expression, likely altering the metabolic flux for phenolamide biosynthesis. This study reveals the role of the MYC2-JAMYB module in JA-mediated rice resistance to BPH.

Herbivore attack elicits jasmonate (JA) signaling which in turn elicits both anti-herbivore plant defenses and growth inhibitions. The resulting growth-defense trade-offs constrain the utility of JA-based plant defense inducers to enhance endogenous pest resistance. Here, we designed and screened selective JA receptor agonists by synthesizing 6-substituted 1-oxoindanoyl isoleucine (In-Ile) conjugates and their free-acid forms, structural mimics of the bioactive hormone (+)-7-iso-jasmonoyl-L-Ile. These compounds differentially activate JA responses through selective binding of specific COI-JAZ coreceptor complexes. Notably, In-Ile treatments enhanced rice resistance to brown planthopper attack, a destructive rice pest, under both laboratory and field conditions, without compromising rice's growth or yield. Mechanistically, this agonist activates the OsMYB55-mediated lignin biosynthesis defense receptor module [OsCOI1a/2-OsJAZs (3,4,6,7,12)] without activating the growth-suppression receptor module (OsCOI1b-OsJAZs). These findings demonstrate that synthetic JA agonists can provide nuanced manipulations of endogenous plant defenses without yield penalties-a promising biorational strategy for pest control in rice.

Microplastics (MPs), particles under 5 mm, are widespread environmental contaminants. Polystyrene (PS), used in many household items, degrades into polystyrene MPs (PS-MPs), which accumulate in the environment. Chronic exposure to waterborne PS-MPs was found to disrupt hepatic lipid metabolism in C57BL/6N mice through inflammatory Kupffer cell polarization and IL-17/NF-κB signaling pathways. While short-term PS-MPs exposure revealed preferential accumulation in the liver and testes, long-term exposure (9-12 weeks) induced significant increases in body fat percentage and hepatic lipid deposition independent of dietary changes. Mechanistically, chronic PS-MPs exposure promoted Kupffer cell polarization toward pro-inflammatory M1 phenotypes, accompanied by upregulated IL-17 expression and suppressed anti-inflammatory cytokines. Western blot analysis demonstrated concurrent elevation of lipid synthesis markers with reduced lipid oxidation and transport proteins. These findings established that PS-MPs accumulation drives hepatic steatosis through dual mechanisms of macrophage-mediated inflammation and impaired lipid homeostasis pathways.

BACKGROUND:The brown planthopper (BPH), Nilaparvata lugens (Stål), is a notorious piercing-sucking herbivore in paddy fields. While jasmonate (JA) signaling is known to mediate rice defense against BPH female adults, the phytohormonal mechanisms underlying resistance to nymphs, which inflict damage solely through feeding, without oviposition, remain unclear. RESULTS:In this study, we demonstrate that BPH nymph infestation elicits the accumulation of both JA and salicylic acid (SA) in rice leaf sheaths, accompanied by significant upregulation of JA- and SA-responsive genes. Overexpression of the JA core transcription factor MYC2 in a susceptible rice cultivar enhanced resistance to nymphs, whereas JA-deficient lines exhibited susceptibility comparable to wild-type plants. In contrast, SA-deficient NahG overexpression plants did not alter nymph resistance, and an NPR1 (SA receptor) mutation unexpectedly increased resistance. Compared to female adult feeding, nymph infestation induced milder upregulation of JA-responsive genes and defensive specialized metabolites. CONCLUSION:Our findings indicate that JA, but not SA signaling, contributes to rice defense against BPH nymphs. © 2025 Society of Chemical Industry.

Micro-and nanoplastics (MNPs) are important environmental pollutants of global concern. While many studies have confirmed that MNPs exposure can disrupt hepatic lipid metabolism in male mice, the effects and mechanisms of MNPs exposure during pregnancy on maternal hepatic glycolipid metabolism remain unclear. In this study, pregnant and non-pregnant mice were randomly divided into three groups: the control group receiving ultrapure water, the low-dose nanoplastics (NPs) exposure group receiving ultrapure water with 0.1 µg·mL-1 NPs, and the high-dose NPs exposure group receiving ultrapure water with 1 µg·mL-1 NPs. Pregnant mice were exposed from gestation day 0 (GD0) and were euthanized on GD13. Non-pregnant mice underwent 14 days of NPs exposure and were then euthanized. Results showed that NPs exposure significantly disrupted glycolipid metabolism in the livers of pregnant mice, resulting in lipid depletion and abnormal glycogen accumulation. However, in non-pregnant mice, NPs exposure only affected glucose metabolism, causing glycogen accumulation without significantly affecting lipid metabolism. These differential effects suggest that pregnant mice are more sensitive to NPs exposure than non-pregnant mice, indicating the need for enhanced environmental safety concerns and protection during pregnancy.

Purpose:Acute myocardial infarction (AMI) is a major contributor to death. The purpose of this study is to explore circulating biomarkers for AMI diagnosis from the perspectives of immunological microenvironment and N6-methyladenosine (m6A) RNA methylation regulation. Patients and Methods:The GSE59867 dataset was used to download platform and probe data for conducting differential analysis of m6A regulators. A diagnostic nomogram was created utilizing the random-forest method and evaluated for predictive power. m6A-related gene patterns were identified, and their immune microenvironment characteristics were analyzed. Peripheral blood samples were obtained for validation in patient-based investigations using RT-qPCR. The association between m6A regulators and clinical parameters was examined via Spearman correlation analysis. Results:With a predictive nomogram model developed using key m6A regulators, two distinct m6A subtypes were identified, showing significant variations in infiltrating immunocyte abundance. In confirmation of the model prediction, examination of patient blood identified METTL3, WTAP, RBM15, ALKBH5, FTO, and FMR1 as novel circulating biomarkers for AMI diagnosis. METTL3 and FTO were identified as promising biomarkers for AMI given that they showed a positive correlation with left ventricular ejection fraction. Conclusion:The study identified six m6A regulators as circulating biomarkers for AMI diagnosis and suggested a potential role for m6A-mediated immune cell infiltration in the pathogenesis of AMI.