Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.
Considerable efforts ...have been made to characterize the potential toxicity of carbon nanomaterials in vitro and in vivo. Many studies have reported various toxicology profiles of carbon nanomaterials. The different results of the cytotoxicity of the carbon-based materials might be related to the differences in the physicochemical properties or structures of carbon nanomaterials, types of target cells and methods of particle dispersion, etc. The reported cytotoxicity effects mainly included reactive oxygen species generation, DNA damage, lysosomal damage, mitochondrial dysfunction and eventual cell death via apoptosis or necrosis. Despite the cellular toxicity, the immunological effects of the carbon-based nanomaterials, such as the pulmonary macrophage activation and inflammation induced by carbon nanomaterials, have been thoroughly studied. The roles of carbon nanomaterials in activating different immune cells or inducing immunosuppression have also been addressed.
Here, we provide a review of the latest research findings on the toxicological profiles of carbon-based nanomaterials, highlighting both the cellular toxicities and immunological effects of carbon nanomaterials. This review provides information on the overall status, trends, and research needs for toxicological studies of carbon nanomaterials.
In recent years, many studies have shown that histone methylation plays an important role in maintaining the active and silent state of gene expression in human diseases. The Jumonji ...domain-containing protein D3 (JMJD3), specifically demethylate di- and trimethyllysine 27 on histone H3 (H3K27me2/3), has been widely studied in immune diseases, infectious diseases, cancer, developmental diseases, and aging related diseases. We will focus on the recent advances of JMJD3 function in human diseases, and looks ahead to the future of JMJD3 gene research in this review.
This study conducts a scientific analysis of 249 literature on the application of brain-computer technology in emotion research. We find that existing researches mainly focus on engineering, computer ...science, neurosciences neurology and psychology. PR China, United States, and Germany have the largest number of publications. Authors can be divided into four groups: real-time functional magnetic resonance imaging (rtfMRI) research group, brain-computer interface (BCI) impact factors analysis group, brain-computer music interfacing (BCMI) group, and user status research group. Clustering results can be divided into five categories, including external stimulus and event-related potential (ERP), electroencephalography (EEG), and information collection, support vector machine (SVM) and information processing, deep learning and emotion recognition, neurofeedback, and self-regulation. Based on prior researches, this study points out that individual differences, privacy risk, the extended study of BCI application scenarios and others deserve further research.
Objectives
Neutrophils are thought to release neutrophil extracellular traps (NETs) to form in response to exogenous bacteria, viruses and other pathogens. However, the mechanisms underlying NET ...formation during sterile inflammation are still unclear. In this study, we would like to identify neutrophil extracellular traps formation during sterile inflammation and tissue injury and associated pathways and its mechanism.
Materials and methods
We identified different injuries such as chemical‐induced and trauma‐induced formation of NETs and investigated mechanism of the formation of NETs in vitro and in vivo during the treatment of mtDNA.
Results
Here, we find the release of mitochondrial DNA (mtDNA) and oxidized mtDNA in acute peripheral tissue trauma models or other chemically induced lung injury, and moreover, endogenous mtDNA and oxidized mtDNA induce the formation of NETs and sterile inflammation. Oxidized mtDNA is a more potent inducer of NETs. Mitochondrial DNA activates neutrophils via cyclic GMP‐AMP synthase (cGAS)‐STING and the Toll‐like receptor 9 (TLR9) pathways and increases the production of neutrophil elastase and extracellular neutrophil‐derived DNA in NETs. Mitochondrial DNA also increases the production of reactive oxygen species (ROS) and expression of the NET‐associated proteins Rac 2 and peptidylarginine deiminase 4 (PAD4).
Conclusions
Altogether, these findings highlight that endogenous mitochondrial DNA inducted NETs formation and subsequent sterile inflammation and the mechanism associated with NET formation.
Tumor-associated macrophages (TAMs) facilitate cancer progression by promoting tumor invasion, angiogenesis, metastasis, inflammatory responses, and immunosuppression. Folate receptor β (FRβ) is ...overexpressed in TAMs. However, the clinical significance of FRβ-positive macrophages in lung cancer remains poorly understood. In this study, we verified that FRβ overexpression in lung cancer TAMs was associated with poor prognosis. We utilized a folate-modified lipoplex comprising a folate-modified liposome (F-PLP) delivering a BIM-S plasmid to target both lung cancer cells and FRβ-positive macrophages in the tumor microenvironment. Transfection of LL/2 cells and MH-S cells with F-PLP/pBIM induced cell apoptosis. Injection of F-PLP/pBIM into LL/2 and A549 lung cancer models significantly depleted FRβ-positive macrophages and reduced tumor growth. Treatment of tumor-bearing mice with F-PLP/pBIM significantly inhibited tumor growth in vivo by inducing tumor cell and macrophage apoptosis, reducing tumor proliferation, and inhibiting tumor angiogenesis. In addition, a preliminary safety evaluation demonstrated a good safety profile of F-PLP/pBIM as a gene therapy administered intravenously. This work describes a novel application of lipoplexes in lung cancer targeted therapy that influences the tumor microenvironment by targeting TAMs.
Compelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in ...nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.
Ammonia plays an important role in cellular metabolism. However, ammonia is considered a toxic product. In bone marrow-derived mesenchymal stem cells, multipotent stem cells with high expression of ...glutamine synthetase (GS) in bone marrow, ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs. As a major nutritional amino acid for biosynthesis, glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation. The activation of mTOR can promote cell entry into S phase, thereby enhancing DNA synthesis and cell proliferation. Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity. Then, the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation. These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.
Phosphorus (P) is a nonrenewable resource, which is one of the major challenges for sustainable agriculture. Although phosphite (Phi) can be absorbed by the plant cells through the Pi transporters, ...it cannot be metabolized by plant and unable to use as P fertilizers for crops. However, transgenic plants that overexpressed phosphite dehydrogenase (PtxD) from bacteria can utilize phosphite as the sole P source. In this study, we aimed to improve the catalytic efficiency of PtxD from
sp.4506 (PtxD
), by directed evolution. Five mutations were generated by saturation mutagenesis at the 139th site of PtxD
and showed higher catalytic efficiency than native PtxD
. The PtxD
showed the highest catalytic efficiency (5.83-fold as compared to PtxD
) contributed by the 41.1% decrease in the
and 2.5-fold increase in the
values. Overexpression of PtxD
in
and rice showed increased efficiency of phosphite utilization and excellent development when phosphite was used as the primary source of P. High-efficiency PtxD transgenic plant is an essential prerequisite for future agricultural production using phosphite as P fertilizers.
•We introduce nonlinear punishment into public goods game.•The synergy of punishment can obviously facilitate cooperation.•The e ect of network degree on the evolution of cooperation is non- ...monotonic.•Cooperation can dominate defection in structured populations.
Punishment has been verified as an important mechanism for promoting cooperation. Ethnographic evidence shows that punishment is coordinated within the group. Thus, we take into account the nonlinear group interaction and propose the synergetic and discounted punishment depicting how fines imposed on defectors nonlinearly accumulate within the group. We further model the replicator dynamics on regular networks and investigate the equilibria of evolutionary dynamics in structured populations. Our results show that cooperation can not be the unique stable equilibrium in well-mixed populations. However, for structured populations, the results indicate that cooperation can be the only stable equilibrium. The interior equilibrium is always an unstable equilibrium in well-mixed and structured populations, which means that cooperation and defection cannot coexist. For low values of β, the high network degree k is favorable to promoting cooperation. On the contrary, the low network degree k becomes beneficial to promoting cooperation with β increases.
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