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Acute renal failure is a common clinical disease in canines, affecting antioxidant levels and decreasing the body's resistance. This study aims to explore the therapeutic mechanism of Nano-selenium in acute renal failure. The histopathological and imaging changes of kidney tissue were observed with the gene and protein expression levels of Keap1, Nrf2, HO-1, and NQO1 in the kidney. According to our findings, adding nano-selenium can effectively reduce the concentration of CRE and BUN in blood and kidney tissues. It increased the activity of GSH-PX and SOD by an effective reduction of MDA. Through pathological and imaging observations, it was found that adding nano-selenium could improve the kidney tissue structure of acute renal failure. The results of the RT-qPCR experiment showed that after the addition of nano-selenium, the mRNA expression of the Keap1 gene decreased significantly. In contrast, the mRNA expression of the Nrf2, HO-1, and NQO1 genes increased significantly. The experimental results were further verified by western blot and immunohistochemical analysis. Hence, the nano-selenium intervention improved kidney function and increased antioxidant levels in canines suffering from acute renal failure with the involvement of the Keap1-Nrf2/ARE signaling pathway.

Abstract The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese‐doped layered double hydroxide (Mn‐LDH) is developed for potent anti‐tumor immunity by reversing TME. Mn‐LDH is synthesized via a one‐step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn‐LDH effectively releases Mn2+ and Mg2+ upon exposure to TME with high levels of H+ and H2O2, which activates synthase‐stimulator of interferon genes pathway and maintains the cytotoxicity of CD8+ T cells respectively, achieving a cascade‐like role in innate and adaptive immunity. The locally administered Mn‐LDH facilitated a “hot” network consisting of mature dendritic cells, M1‐phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn‐LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME‐modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next‐generation cancer immunotherapy.

Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.

Abstract The integration of 2D ferroelectric materials with 2D photoelectric materials presents a promising avenue for addressing issues related to controlled doping and device integration in layered semiconductors. The reversible and non‐volatile residual polarization inherent to ferroelectrics can provide stable n‐ or p‐type doping for 2D semiconductors. Despite advances in doping strategies for 2D materials, existing techniques, and post‐doping characterization methodologies exhibit limitations, including the challenge of achieving high‐resolution graphical depictions of doped structures. Here, a WS2/CuInP2S6 heterostructure is demonstarted whereby the residual polarization of ferroelectric CuInP2S6 regions with anti‐parallel directions supplies screening charges of opposite signs to WS2 monolayers. This notably alters the ratio of neutral excitons and negatively charged trions within the recombination luminescence of the direct‐gap semiconductor, thereby offering a viable approach for controllable, non‐volatile modulation in 2D systems. Beyond proposing a feasible strategy for patterned doping and effective regulation in 2D semiconductors through interface engineering, this work enhances the understanding of the interplay between ferroelectrics and semiconductors.

Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology’s potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.

Abstract We obtain new vacuum static black hole solutions with anisotropic horizons in Einstein–Gauss–Bonnet gravity with a negative cosmological constant in five dimensions. The translational invariance along one direction on the 3-dimensional horizon cross section is broken. The Gauss–Bonnet coupling $$\alpha $$ α is at the critical point where there is one single AdS vacuum. These solutions does not appear in the form of a warped product, i.e. they lack a common warping factor, and the metric contains 2 arbitrary functions, h(r) of the radial coordinate r and H(y) of the horizon coordinate y – some degeneracy in the metric. The nontrivial horizon and the degeneracy may be closely related to the critical value of $$\alpha $$ α . We introduce the process of obtaining the solutions and some of their properties, and also prove a uniqueness theorem for the case when there is a common warping factor for the rest two directions.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Background: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case–control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. Results: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines’ use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62–2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18–3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100–25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80–2105.83]) by network meta-analysis. Conclusions: Our findings show a significant association between anthracyclines’ use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents’ metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.