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Hollow CuS nanoparticles can achieve photothermal and photodynamic therapy (PDT) in tumor treatment. However, excessive GSH in the tumor cells will consume the reactive oxygen species produced by PDT and reduce the PDT effect. Cisplatin is a broad-spectrum antineoplastic drug that can be used in a variety of tumor treatments. However, cisplatin is cytotoxic to normal cells while it kills tumor cells. Therefore, we construct Pt(IV) complexes loaded hollow CuS nanoparticles to attenuate the toxicity of cisplatin and enhance the PDT effect of the hollow CuS nanoparticles. The nanoparticles were proved to be able to accumulate around the tumor site through the enhanced permeability and retention (EPR) effect to achieve a synergistic chemo/photothermal/photodynamic therapy.
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AIM: To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin (AST). METHODS: ICR mice were intraperitoneally injected NaIO3, CY-09, AST successively and divided into 5 groups, including the control, NaIO3, NaIO3+CY-09, NaIO3+AST, and NaIO3+CY-09+AST groups. Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry, enzyme linked immunosorbent assay (ELISA), and Western blotting. Retinal pigment epithelium cell line (ARPE-19 cells) and mouse photoreceptor cells line (661W cells) were also treated with NaIO3, CY-09, and AST successively. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay. Apoptosis was analyzed by flow cytometry. Changes in autophagosome morphology were observed by transmission electron microscopy. Quantitative polymerase chain reaction (qPCR) was used to detect NLRP3 and caspase-1. NLRP3, caspase-1, cleaved caspase-1, p62, Beclin-1, and LC3 protein levels were measured by Western blotting. IL-1ß and IL-18 were measured by ELISA. RESULTS: Compared with the control group, the activity of NaIO3-treated 661W cells decreased within 24 and 48h, apoptosis increased, NLRP3, caspase-1, IL-1ß and IL-18 levels increased, and autophagy-related protein levels increased (P<0.05). Compared with NaIO3 group, CY-09 and AST inhibited apoptosis (P<0.05), reduced NLRP3, caspase-1, IL-1ß and IL-18 expression (P<0.05), and inhibited autophagy. Compared with the other groups, CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62, Beclin-1, and LC3 in vitro and in vivo (P<0.05). CONCLUSION: CY-09 and AST inhibit NaIO3-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo. CY-09 and AST may protect retina from inflammatory injury.
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This study presents a scientometric analysis of the intersection between rehabilitation science and artificial intelligence (AI) technologies, using data from the Web of Science (WOS) database from 2002 to 2022. The analysis employed a comprehensive search query with key AI-related terms, focusing on a wide range of publications in rehabilitation science. Utilizing the Citespace tool, the study visualizes and quantifies the relationships between key terms, identifies research trends, and assesses the impact of AI technologies in rehabilitation science. Findings reveal a significant increase in AI-related research in this field, particularly from 2017 onwards, peaking in 2021. The United States has been a leading contributor, followed by countries like England, Australia, Germany, and Canada. Major institutional contributions come from Harvard University and the Pennsylvania Commonwealth System of Higher Education, among others. A keyword co-occurrence network constructed through Citespace identifies nine distinct hot topics and various research frontiers, highlighting evolving focus areas within the field. Burst analysis of keywords indicates a shift from performance and injury-related research to an increasing emphasis on AI and deep learning in recent years. The study also predicts the potential impact of papers, spotlighting works by Kunze KN and others as significantly influencing future research directions. Additionally, it examines the evolution of knowledge bases in AI-related rehabilitation science research, revealing a multidisciplinary core that includes neurology, rehabilitation, and ophthalmology, extending to complementary fields such as medicine and social sciences. This scientometric analysis provides a comprehensive overview of AI's application in rehabilitation science, offering insights into its evolution, impact, and emerging trends over the past two decades. The findings suggest strategic directions for future research, policy-making, and interdisciplinary collaboration in rehabilitation science and AI.
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Natural resources have a significant impact on economic and political landscapes of developing countries which determines environmental sustainability. This study explores the convoluted connection between governance and natural resources, examining how resource abundance might influence governance quality. The main components of this dynamic that the theoretical framework considers are the Rentier effects, the repression effects, and the obstruction of modernization. This study creates a governance index applying principal component analysis (PCA) on several governance characteristics, such as political stability, rule of law, government efficacy, regulation and control of corruption, to measure governance comprehensively. Natural resource exports, rents, and the differentiation between renewable and non-renewable natural resources are the three proxies used to quantify natural resources, providing a more nuanced view. To calculate the effect of renewable and non-renewable natural resources on governance in developing nations, the econometric methodology uses a dynamic panel model and system GMM. This analysis reveals that the ability of renewable resources to promote inclusive development has a favourable impact on governance. On the other hand, non-renewable resources show a negative correlation, mainly because of their vulnerability to swings in the world price and their propensity to consolidate power and promote corruption. The significance of differentiating between natural resource types is highlighted in this study, along with the possible advantages of renewable resources for governance and the disadvantages of an over-reliance on non-renewable resources. Policymakers, researchers, and practitioners interested in the development and governance difficulties encountered by resource-rich developing nations can benefit greatly from this research's larger and more complex understanding of the link between natural resources and governance.
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Conservación de los Recursos Naturales , Recursos Naturales , Países en DesarrolloRESUMEN
Hematopoietic cell kinase (Hck), a non-receptor tyrosine kinase belonging to the Src kinase family, is intricately linked to the pathogenesis of numerous human diseases, with a particularly pronounced association with cancer. Hck not only directly impacts the proliferation, migration, and apoptosis of cancer cells but also interacts with JAK/STAT, MEK/ERK, PI3K/AKT, CXCL12/CXCR4, and other pathways. Hck also influences the tumor microenvironment to facilitate the onset and progression of cancer. This paper delves into the functional role and regulatory mechanisms of Hck in various solid tumors. Additionally, it explores the implications of Hck in hematological malignancies. The review culminates with a summary of the current research status of Hck inhibitors, the majority of which are in the pre-clinical phase of investigation. Notably, these inhibitors are predominantly utilized in the therapeutic management of leukemia, with their combinatorial potential indicating promising avenues for future research. In conclusion, this review underscores the significance of the mechanism of Hck in solid tumors. This insight is crucial for comprehending the current research trends regarding Hck: targeted therapy against Hck shows great promise in both diagnosis and treatment of malignant tumors. Further investigation into the role of Hck in cancer, coupled with the development of specific inhibitors, has the potential to revolutionize approaches to cancer treatment.
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Progresión de la Enfermedad , Neoplasias , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-hck , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Neoplasias/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Animales , Proteínas Proto-Oncogénicas c-hck/metabolismo , Proteínas Proto-Oncogénicas c-hck/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral , Terapia Molecular DirigidaRESUMEN
This study examines the dynamic relationship between global value chain integration, and carbon emissions, in 57 developing economies from 2000 to 2018. Our results show a multipart link between GVC involvement and carbon emissions. Specifically, forward participation, which involves domestic content in foreign exports, offers the potential to reduce emissions, whereas backward participation, defined by foreign content in domestic exports, typically increases emissions. This imbalance draws attention to the dual nature of using mineral resources, which can contribute to and mitigate environmental damage depending on the extent of GVC engagement. The NARDL model employed in the study also reveals the dynamic and nonlinear responses of carbon emissions to variations in the utilization of mineral resources within GVCs. Our findings show that positive shocks to mineral resources use within GVCs negatively influence carbon emissions, while adverse shocks have less impact. The results have significant policy implications, indicating that developing nations should prioritize environmental sustainability while planning their GVC participation. This entails promoting value-added mining resource use initiatives and pushing for strict environmental regulations in GVCs. Our results also highlight the significance of implementing customized measures to mitigate economic activity's asymmetric and nonlinear impacts on environmental quality. It enlightens policymakers in developing nations on balancing environmental conservation and economic growth in a global economy that is becoming more interconnected.
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Conservación de los Recursos Naturales , Carbono/análisisRESUMEN
Anxiety disorders are the most common psychiatric condition, but the etiology of anxiety disorders remains largely unclear. Our previous studies have shown that neuroplastin 65 deficiency (NP65-/-) mice exhibit abnormal social and mental behaviors and decreased expression of tryptophan hydroxylase 2 (TPH2) protein. However, whether a causal relationship between TPH2 reduction and anxiety disorders exists needs to be determined. In present study, we found that replenishment of TPH2 in dorsal raphe nucleus (DRN) enhanced 5-HT level in the hippocampus and alleviated anxiety-like behaviors. In addition, injection of AAV-NP65 in DRN significantly increased TPH2 expression in DRN and hippocampus, and reduced anxiety-like behaviors. Acute administration of exogenous 5-HT or HTR3 agonist SR57227A in hippocampus mitigated anxiety-like behaviors in NP65-/- mice. Moreover, replenishment of TPH2 in DRN partly repaired the impairment of long-term potentiation (LTP) maintenance in hippocampus of NP65-/- mice. Finally, we found that loss of NP65 lowered transcription factors Lmx1b expression in postnatal stage and replenishment of NP65 in DRN reversed the decrease in Lmx1b expression of NP65-/- mice. Together, our findings reveal that NP65 deficiency induces anxiety phenotype by downregulating DRN-hippocampus serotonergic-HTR3 transmission. These studies provide a novel and insightful view about NP65 function, suggesting an attractive potential target for treatment of anxiety disorders.
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Ansiedad , Núcleo Dorsal del Rafe , Hipocampo , Ratones Noqueados , Receptores de Serotonina 5-HT3 , Serotonina , Triptófano Hidroxilasa , Animales , Núcleo Dorsal del Rafe/metabolismo , Hipocampo/metabolismo , Ansiedad/metabolismo , Serotonina/metabolismo , Ratones , Masculino , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/metabolismo , Triptófano Hidroxilasa/deficiencia , Receptores de Serotonina 5-HT3/metabolismo , Receptores de Serotonina 5-HT3/genética , Ratones Endogámicos C57BL , Fenotipo , Potenciación a Largo PlazoRESUMEN
INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glucocorticoides , Tuberculosis , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Masculino , Femenino , Anciano , Adulto , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Adulto Joven , Anciano de 80 o más Años , Adolescente , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , China , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéuticoRESUMEN
Asparagine, an important amino acid in mammals, is produced in several organs and is widely used for the production of other nutrients such as glucose, proteins, lipids, and nucleotides. Asparagine has also been reported to play a vital role in the development of cancer cells. Although several types of cancer cells can synthesise asparagine alone, their synthesis levels are insufficient to meet their requirements. These cells must rely on the supply of exogenous asparagine, which is why asparagine is considered a semi-essential amino acid. Therefore, nutritional inhibition by targeting asparagine is often considered as an anti-cancer strategy and has shown success in the treatment of leukaemia. However, asparagine limitation alone does not achieve an ideal therapeutic effect because of stress responses that upregulate asparagine synthase (ASNS) to meet the requirements for asparagine in cancer cells. Various cancer cells initiate different reprogramming processes in response to the deficiency of asparagine. Therefore, it is necessary to comprehensively understand the asparagine metabolism in cancers. This review primarily discusses the physiological role of asparagine and the current progress in the field of cancer research.
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Leucemia , Neoplasias , Animales , Asparagina , Aminoácidos , Glucosa , MamíferosRESUMEN
Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animales , Especies Reactivas de Oxígeno , Polímeros/química , Luminol , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Nanopartículas/química , Inflamación/diagnóstico por imagen , Inflamación/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/químicaRESUMEN
PURPOSE: The purpose of this study was to understand and analyze the risk factors of peripherally inserted central catheter (PICC)-related venous thrombosis in adult patients with cancer. METHODS: This observational cohort study included adult patients with cancer who underwent color Doppler ultrasound at the Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province, from January 1, 2017 to December 31, 2021. Univariate and multivariate logistic regression analyses were performed to determine the risk factors of PICC-related venous thrombosis. RESULTS: After risk adjustment, multivariate logistic regression analysis revealed statistically significant associations between PICC-related venous thrombosis and age > 65 years old (OR: 1.791, CI: 1.343-2.389), male sex (OR: 1.398, CI: 1.057-1.849), white blood cell count > 9.5 × 109 /L (OR: 1.422, CI: 1.041-1.942), APTT < 25 s (OR: 2.006, CI: 1.431-2.811), gastrointestinal tumor (OR: 2.191, CI: 1.406-3.414), infection (OR:7.619, CI: 5.783-10.037), the use of cisplatin (OR: 2.374, CI: 1.714-3.214), vincristine (OR: 2.329, CI: 1.447-3.749), the use of polyurethane (OR: 2.449, CI: 1.863-3.219) and open-ended catheters (OR:1.660, CI: 1.131-2.439), keeping time of the catheter (days) (OR: 1.003, CI: 1.001-1.005) were associated with PICC-related venous thrombosis. CONCLUSION: We identified that the presence of age > 65 years old, male sex, white blood cell count > 9.5 × 109 /L, APTT < 25 s, gastrointestinal tumor, infection, the use of cisplatin and vincristine, the use of polyurethane, open-ended catheters and keeping time of the catheter (days), were associated with PICC-related venous thrombosis.
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Diabetic chronic wounds are characterized by local hypoxia, impaired angiogenesis, and bacterial infection. In situ, self-supply of dissolved oxygen combined with the elimination of bacteria is urgent and challenging for chronic nonhealing wound treatment. Herein, an oxygen-generating system named HA-L-NB/PFE@cp involving biological photosynthetic chloroplasts (cp)/conjugated polymer composite nanoparticles (PFE-1-NPs@cp) and light-triggered hyaluronic acid-based (HA-L-NB) hydrogel for promoting diabetic wound healing is introduced. Briefly, conjugated polymer nanoparticles (PFE-1-NPs) possess unique light harvesting ability, which accelerates the electron transport rates in photosystem II (PS II) by energy transfer, elevating photosynthesis beyond natural chloroplasts. The enhanced release of oxygen can greatly relieve hypoxia, promote cell migration, and favor antibacterial photodynamic therapy. Additionally, the injectable hydrogel precursors are employed as a carrier to deliver PFE-1-NPs@cp into the wound. Under light irradiation, they quickly form a gel by S-nitrosylation coupling reaction and in situ anchor on tissues through amine-aldehyde condensation. Both in vitro and in vivo assays demonstrate that the oxygen-generating system can simultaneously relieve wound hypoxia, eliminate bacteria, and promote cell migration, leading to the acceleration of wound healing. This study provides a facile approach to develop an enhanced oxygen self-sufficient system for promoting hypoxic tissue, especially diabetic wound healing.
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Diabetes Mellitus , Hidrogeles , Humanos , Fotosíntesis , Hipoxia , Oxígeno , Ácido HialurónicoRESUMEN
Bone defect regeneration is one of the great clinical challenges. Suitable bioactive composite scaffolds with high biocompatibility, robust new-bone formation capability and degradability are still required. This work designs and synthesizes an unprecedented bioactive conjugated polymer PT-C3 -NH2 , demonstrating low cytotoxicity, cell proliferation/migration-promoting effect, as well as inducing cell differentiation, namely regulating angiogenesis and osteogenesis to MC3T3-E1 cells. PT-C3 -NH2 is incorporated into polylactic acid-glycolic acid (PLGA) scaffolds, which is decorated with caffeic acid (CA)-modified gelatin (Gel), aiming to improve the surface water-wettability of PLGA and also facilitate to the linkage of conjugated polymer through catechol chemistry. A 3D composite scaffold PLGA@GC-PT is then generated. This scaffold demonstrates excellent bionic structures with pore size of 50-300 µm and feasible biodegradation ability. Moreover, it also exhibites robust osteogenic effect to promote osteoblast proliferation and differentiation in vitro, thus enabling the rapid regeneration of bone defects in vivo. Overall, this study provides a new bioactive factor and feasible fabrication approach of biomimetic scaffold for bone regeneration.
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Polímeros , Andamios del Tejido , Andamios del Tejido/química , Biónica , Osteogénesis , Regeneración ÓseaRESUMEN
Breast cancer is the most common cancer affecting women worldwide. Investigating metabolism in breast cancer may accelerate the exploitation of new therapeutic options for immunotherapies. Metabolic reprogramming can confer breast cancer cells (BCCs) with a survival advantage in the tumor microenvironment (TME) and metabolic alterations in breast cancer, and the corresponding metabolic byproducts can affect the function of tumor-associated macrophages (TAMs). Additionally, TAMs undergo metabolic reprogramming in response to signals present in the TME, which can affect their function and breast cancer progression. Here, we review the metabolic crosstalk between BCCs and TAMs in terms of glucose, lipids, amino acids, iron, and adenosine metabolism. Summaries of inhibitors that target metabolism-related processes in BCCs or TAMs within breast cancer have also served as valuable inspiration for novel therapeutic approaches in the fight against this disease. This review provides new perspectives on targeted anticancer therapies for breast cancer that combine immunity with metabolism.
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Neoplasias de la Mama , Neoplasias , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos/metabolismo , Neoplasias/metabolismo , Inmunoterapia , Mama/metabolismo , Microambiente Tumoral/fisiologíaRESUMEN
Cardiovascular diseases have posed a great threat to human health. Fortunately, gene therapy holds great promise in the fight against cardiovascular disease (CVD). In gene therapy, it is necessary to select the appropriate carriers to deliver the genes to the target cells of the target organs. There are usually two types of carriers, viral carriers and non-viral carriers. However, problems such as high immunogenicity, inflammatory response, and limited loading capacity have arisen with the use of viral carriers. Therefore, scholars turned their attention to non-viral carriers. Among them, nanocarriers are highly valued because of their easy modification, targeting, and low toxicity. Despite the many successes of gene therapy in the treatment of human diseases, it is worth noting that there are still many problems to be solved in the field of gene therapy for the treatment of cardiovascular diseases. In this review, we give a brief introduction to the common nanocarriers and several common cardiovascular diseases (arteriosclerosis, myocardial infarction, myocardial hypertrophy). On this basis, the application of gene delivery nanocarriers in the treatment of these diseases is introduced in detail.
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Sistema Cardiovascular , Infarto del Miocardio , Nanopartículas , Humanos , Portadores de Fármacos , Terapia Genética , Sistemas de Liberación de MedicamentosRESUMEN
Covalent organic framework materials (COFs), as a new type of organic porous material, not only have the characteristics of flexible structure, abundant resources, environmental friendliness, etc., but also have the characteristics of a regular structure and uniform pore channels, so they have broad application prospects in secondary batteries. Their functional group structure, type, and number of active sites play a crucial role in the performance of different kinds of batteries. Therefore, this article starts from these aspects, summarizes the application and research progress of the COF anode materials used in lithium-ion batteries, sodium-ion batteries, and potassium-ion batteries in recent years, discusses the energy storage mechanism of COF materials, and expounds the application prospects of COF electrodes in the field of energy storage.
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Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation. The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes, which is involved in atherogenesis.
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The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc- axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.