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The widespread presence of microplastics (MPs) in the environment poses a significant threat to biological survival and human health. However, our understanding of the toxic effects of MPs on the kidneys remains limited. This study aimed to investigate the underlying mechanism of the toxic effects of MPs on the kidneys using an ischemia–reperfusion (IR) mouse model. Four‐week‐old ICR mice were exposed to 0.5 μm MPs for 12 weeks prior to IR injury. The results showed that MPs exposure could aggravate the IR‐induced damage to renal tubules and glomeruli. Although there were no significant changes in blood urea nitrogen and serum creatinine levels 7 days after IR, MPs treatment resulted in a slight increase in both parameters. In addition, the expression levels of inflammatory factors (MCP‐1 and IL‐6) at the mRNA level, as well as macrophage markers (CD68 and F4/80), were significantly higher in the MPs + IR group than in the Sham group after IR. Furthermore, MPs exposure exacerbated IR‐induced renal fibrosis. Importantly, the expression of pyroptosis‐related genes, including NLRP3, ASC, GSDMD, cleaved caspase‐1, and IL‐18, was significantly upregulated by MPs, indicating that MPs exacerbate pyroptosis in the context of renal IR. In conclusion, our findings suggest that MPs exposure can aggravate renal IR‐induced pyroptosis by activating NLRP3‐GSDMD signaling. [ABSTRACT FROM AUTHOR]

In recent years, microplastics (MPs) have gained significant attention as a persistent environmental pollutant resulting from the decomposition of plastics, leading to their accumulation in the human body. The liver, particularly of individuals with type 2 diabetes mellitus (T2DM), is known to be more susceptible to the adverse effects of environmental pollutants. Therefore, to investigate the potential impact of MPs on the liver of diabetic mice and elucidate the underlying toxicological mechanisms, we exposed db/db mice to 0.5 μm MPs for 3 months. Our results revealed that MPs exposure resulted in several harmful effects, including decreased body weight, disruption of liver structure and function, elevated blood glucose levels, impaired glucose tolerance, and increased glycogen accumulation in the hepatic tissue of the mice. Furthermore, MPs exposure was found to promote hepatic gluconeogenesis by perturbing the PP2A/AMPK/HNF4A signaling pathway. In addition, MPs disrupt redox balance, leading to oxidative damage in the liver. This exposure also disrupted hepatic lipid metabolism, stimulating lipid synthesis while inhibiting catabolism, ultimately resulting in the development of fatty liver. Moreover, MPs were found to induce liver fibrosis by activating the Wnt/β‐catenin signaling pathway. Furthermore, MPs influenced adaptive thermogenesis in brown fat by modulating the expression of uncoupling protein 1 (UCP1) and genes associated with mitochondrial oxidative respiration thermogenesis in brown fat. In conclusion, our study demonstrates that MPs induce oxidative damage in the liver, disturb glucose and lipid metabolism, promote hepatic fibrosis, and influence adaptive thermogenesis in brown fat in diabetic mice. These findings underscore the potential adverse effects of MPs on liver health in individuals with T2DM and highlight the importance of further research in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most prevalent malignancy in women. With the improvement of medical treatment, breast cancer has become one of the solid tumors with the best curative effect. However, triple-negative breast cancer is not sensitive to conventional treatment due to its high invasiveness, resulting in a poorer prognosis than other types. The antibodies of programmed death receptor 1 and its ligands represent a new option as immunotherapy for patients with triple negative breast cancer. However, some recent clinical data suggest that a large proportion of patients exhibit primary or acquired resistance to treatment with programmed death receptor antibodies. In this review, we discuss the mechanisms that lead to resistance and also summarize potential strategies to overcome the resistance, improving the therapeutic efficacy of programmed death receptor 1 and its ligand-based antibodies in triple negative breast cancer. Triple-negative breast cancer (TNBC) is characterized by a high rate of systemic metastasis, insensitivity to conventional treatment and susceptibility to drug resistance, resulting in a poor patient prognosis. The immune checkpoint inhibitors (ICIs) represented by antibodies of programmed death receptor 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have provided new therapeutic options for TNBC. However, the efficacy of PD-1/PD-L1 blockade monotherapy is suboptimal immune response, which may be caused by reduced antigen presentation, immunosuppressive tumor microenvironment, interplay with other immune checkpoints and aberrant activation of oncological signaling in tumor cells. Therefore, to improve the sensitivity of TNBC to ICIs, suitable patients are selected based on reliable predictive markers and treated with a combination of ICIs with other therapies such as chemotherapy, radiotherapy, targeted therapy, oncologic virus and neoantigen-based therapies. This review discusses the current mechanisms underlying the resistance of TNBC to PD-1/PD-L1 inhibitors, the potential biomarkers for predicting the efficacy of anti-PD-1/PD-L1 immunotherapy and recent advances in the combination therapies to increase response rates, the depth of remission and the durability of the benefit of TNBC to ICIs. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) is a typical reactive peroxide that is widely used in food preservation but may cause serious harm to human health. Thus, a simple, efficient and accurate method for H2O2 assay is essential. In this work, a dual Eu-MOFs-based ratiometric fluorescence sensor, a logic gate-based advanced analytical method, and a dual MOFs-loaded paper microchip for visual H2O2 assay were constructed. The H2O2 sensor was response-sensitive (limit of detection: 0.14 μM) and linearly responsive in the concentration range of 0.001–1 mM (r > 0.99). Then, an advanced AND gate logic device was established to monitor H2O2 concentration. Moreover, the paper-based microchip realized the point-of-care visual H2O2 assay via ratiometric chromaticity assisted by a portable smartphone-based visual assay device. The microchip consumes only 5 μL of sample and demonstrates long-term stability for over 30 days along with response-sensitivity. Both the MOF dispersion-based ratiometric fluorescence sensor and the paper microchip realized an accurate and precise assay of H2O2 (the recovery was 88.2–105.5% and RSD < 9.3%). To the best of our knowledge, this is the first report of a dual MOFs-based ratiometric fluorescent H2O2 sensor, an advanced logic gate-based analytical method, and a paper-based microchip for visual point-of-care H2O2 assay. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is a versatile model organism for exploring complex biological systems. Microbes and the external environment can affect the nervous system and drive behavioral changes in C. elegans . For better survival, C. elegans may develop behavioral immunity to avoid potential environmental pathogens. However, the molecular and cellular mechanisms underlying this avoidance behavior are not fully understood. The dissection of sensorimotor circuits in behavioral immunity may promote advancements in research on the neuronal connectome in uncovering neuronal regulators of behavioral immunity. In this review, we discuss how the nervous system coordinates behavioral immunity by translating various pathogen-derived cues and physiological damage to motor output in response to pathogenic threats in C. elegans . This understanding may provide insights into the fundamental principles of immune strategies that can be applied across species and potentially contribute to the development of novel therapies for immune-related diseases., Competing Interests: The authors declare that they have no competing interests., (© 2024 Wang et al.)

Immune cells are essential for initiating and developing the fibrotic process by releasing cytokines and growth factors that activate fibroblasts and promote extracellular matrix deposition. Immunometabolism describes how metabolic alterations affect the function of immune cells and how inflammation and immune responses regulate systemic metabolism. The disturbed immune cell function and their interactions with other cells in the tissue microenvironment lead to the origin and advancement of fibrosis. Understanding the dysregulated metabolic alterations and interactions between fibroblasts and the immune cells is critical for providing new therapeutic targets for fibrosis. This review provides an overview of recent advances in the pathophysiology of fibrosis from the immunometabolism aspect, highlighting the altered metabolic pathways in critical immune cell populations and the impact of inflammation on fibroblast metabolism during the development of fibrosis. We also discuss how this knowledge could be leveraged to develop novel therapeutic strategies for treating fibrotic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Chen, Huang, Zhang, Zheng and Xie.)