Cuiqing Liu

RSV alleviates liver injury by regulating HSF1 to inhibit lipid deposition and necroptosis.

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.

Myocardial infarction causes structural damage that impairs both the mechanical and electrophysiological functions of the heart. Modulating the mechanical and electrical properties of biomaterials represents a promising strategy for myocardial repair. This review systematically outlines the mechanisms and design principles of such regulation through three integrated approaches: mechanical modulation, electrical modulation, and mechano-electrical coordination. Mechanically, tuning stiffness, elasticity, and anisotropy enhances cellular alignment, tissue integration, and structural support. Electrically, regulating conductivity and anisotropy facilitates synchronous signal propagation and functional restoration. The coordinated strategy enables synergistic optimization of mechanical and electrical properties, thereby improving repair outcomes. Furthermore, biomimetic in vitro models, including cardiac organoids and heart-on-a-chip systems, provide physiologically relevant platforms for evaluating material performance. This review provides foundational insights and design principles for advancing myocardial repair via mechano-electrical biomaterial engineering.

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.

The rising prevalence of metabolic diseases represents a global health challenge, with metabolically unhealthy normal-weight (MUHNW) individuals remaining

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 (PM_2.5), 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 PM_2.5 exposure on nonobese offspring, particularly in iWAT plasticity, and underlying cellular mechanisms remain poorly understood. Here, we revealed that maternal PM_2.5 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 PM_2.5 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 PM_2.5 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 PM_2.5 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.

China has implemented a series of clean air policies, resulting in improved air quality since 2013. However, there remains a paucity of national prospective evidence regarding the relationship between fine particulate matter (PM_2.5) and kidney disease (KD) incidence in China, as well as the potential mediating effects of lipid profiles in this association. This study aimed to assess the association of decreased PM_2.5 concentration and KD incidence in China from 2013 to 2020. Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS), we included 15,368 participants who were free of KD in 2013 and followed up until 2020. For each participant, we calculated the 3-year and 2-year average PM_2.5 concentrations. The Cox proportional hazards model was employed to estimate the association between PM_2.5 exposure and KD incidence. Mediation analyses were conducted using eight lipid indices, and subgroup analyses were performed. The annual average PM_2.5 concentration for CHARLS participants reduced from 61.72 μg/m³ in 2013 to 32.75 μg/m³ in 2020. A reduction of 5 μg/m³ in 3-year and 2-year average PM_2.5 concentrations was associated with 14.3% (hazard ratio [HR]: 0.857, 95% confidence interval [CI]: 0.841, 0.873) and 14.4% (HR: 0.856, 95% CI: 0.840, 0.873) reductions in KD incidence in the fully adjusted models. The TyG-BMI and TyG-WHtR indices exhibited small mediating effects of 7.36% (95% CI: 2.35%, 12.38%) and 4.48% (95% CI: 0.51%, 8.45%) on the relationship of PM_2.5–KD, while other indicators did not demonstrate significant mediation. The findings of this study suggest that reductions in PM_2.5 concentration were associated with a decreased incidence of KD during the period from 2013 to 2020. The implementation of clean air policies since 2013 may have contributed to the decrease in chronic diseases like KD.

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.

Emerging evidence indicates that prenatal exposure to fine particulate matter (PM_2.5) may program metabolic syndrome (MS) in adult offspring. However, the metabolic response to the second hit of a high-fat diet (HFD) (prenatal PM_2.5 exposure as the first hit) in adult offspring and its underlying mechanisms remain poorly understood. Using a whole-body inhalational exposure system, we achieved the following observations. First, prenatal PM_2.5 exposure significantly increased the fat mass, inhibited the insulin signaling pathway in chow diet (CD)-fed offspring, and exacerbated HFD-induced metabolic disorders evidenced by impaired insulin signaling in metabolic organs like liver, epididymal white adipose tissue (eWAT), and brown adipose tissue (BAT). Second, prenatal PM_2.5 exposure enhanced hepatic lipid accumulation and hypertrophy of adipocytes in eWAT and BAT, accompanied by lipid metabolic disorders in the liver and eWAT. Finally, prenatal exposure to PM_2.5 exaggerated HFD-induced cellular senescence in both hepatic and eWAT, as well as cell cycle arrest in BAT, which ultimately led to the activation of chronic inflammation in offspring. In conclusion, prenatal exposure to PM_2.5 increased the vulnerability to the second hit of HFD feeding in adult offspring, in which chronic inflammation triggered by cellular senescence may be involved. These findings underscore the heightened vulnerability to metabolic diseases in individuals following early life exposure to air pollution, particularly in the setting of compounding with a high-fat dietary pattern.