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Periodontitis is a prevalent chronic disease that results in loss of periodontal ligament and bone resorption. Triggered by pathogens and prolonged inflammation, periodontitis is modulated by the immune system, especially pro-inflammatory cells, such as T helper (Th) 17 cells. Originated from CD4 + Th cells, Th17 cells play a central role for they drive and regulate periodontal inflammation. Cytokines secreted by Th17 cells are also major players in the pathogenesis of periodontitis. Given the importance of Th17 cells, modulators of Th17 cells are of great clinical potential and worth of discussion. This review aims to provide an overview of the current understanding of the effect of Th17 cells on periodontitis, as well as a brief discussion of current and potential therapies targeting Th17 cells. Lastly, we highlight this article by summarizing the causal relationship between A20 (encoded by TNFAIP3 ), an anti-inflammatory molecule, and Th17 cell differentiation.

Background Exosome-mediated crosstalk between cancer cells and immune cells contributes to tumor growth. In this study, we investigated the mechanism underlying the exosome-mediated immune escape of colorectal cancer (CRC) cells from natural killer (NK) cells via the transfer of long noncoding RNAs (lncRNAs). Methods An epithelial–mesenchymal transition (EMT) model of SW480 cells was established by transforming growth factor beta (TGF-β), followed by the assessment of the effect of EMT-derived exosomes (EMT-exo) on the functions of NK cells. RNA sequencing was performed to identify exosomal lncRNAs and target genes. The function of exosomal lncRNAs in tumor growth was further verified in vivo. Results EMT-exo suppressed the proliferation, cytotoxicity, IFN-γ production, and perforin-1 and granzyme B secretion of NK cells. RNA sequencing revealed that SNHG10 expression was upregulated in EMT-exo compared with that in non-EMT-exo. Moreover, SNHG10 expression was upregulated in tumor tissues in CRC, which was associated with poor prognosis. Overexpression of SNHG10 in exosomes (oe-lnc-SNHG10 exo) significantly suppressed the viability and cytotoxicity of NK cells. Transcriptome sequencing of NK cells revealed that the expression levels of 114 genes were upregulated in the oe-lnc-SNHG10 exo group, including inhibin subunit beta C ( INHBC ), which was involved in the TGF-β signaling pathway. Si-INHBC treatment abrogated the effect of oe-lnc-SNHG10 exo on NK cells. oe-lnc-SNHG10 exo induced tumor growth and upregulated INHBC expression in mice and downregulated the expression of perforin, granzyme B, and NK1.1 in tumor tissues. Conclusions The CRC cell-derived exosomal lncRNA SNHG10 suppresses the function of NK cells by upregulating INHBC expression. This study provides evidence that exosomal lncRNAs contribute to immune escape by inducing NK cell inhibition and proposes a potential treatment strategy for CRC.

Graphene quantum dots (GQDs) have attracted significant attention in biomedicine, while extensive investigations have revealed a reverse regarding the potential biotoxicity of GQDs. In order to supplementing the understanding of the toxicity profile of GQDs, this study employs a molecular dynamics (MD) simulation approach to systematically investigate the potential toxicity of both GQDs and Graphene Oxide Quantum Dots (GOQDs) on the Anterior Gradient Homolog 2 (AGR2) protein, a key protein capable of protecting the intestine. We construct two typical simulation systems, in which an AGR2 protein is encircled by either GQDs or GOQDs. The MD results demonstrate that both GQDs and GOQDs can directly make contact with and even cover the active site (specifically, the Cys81 amino acid) of the AGR2 protein. This suggests that GQDs and GOQDs have the capability to inhibit or interfere with the normal biological interaction of the AGR2 active site with its target protein. Thus, GQDs and GOQDs exhibit potential detrimental effects on the AGR2 protein. Detailed analyses reveal that GQDs adhere to the Cys81 residue due to van der Waals (vdW) interaction forces, whereas GOQDs attach to the Cys81 residue through a combination of vdW (primary) and Coulomb (secondary) interactions. Furthermore, GQDs aggregation typically adsorb onto the AGR2 active site, while GOQDs adsorb to the active site of AGR2 one by one. Consequently, these findings shed new light on the potential adverse impact of GQDs and GOQDs on the AGR2 protein via directly covering the active site of AGR2, providing valuable molecular insights for the toxicity profile of GQD nanomaterials.

Migrasomes are a newly discovered class of extracellular vesicles, yet their roles in colorectal cancer (CRC) metastasis remain poorly understood. This study aimed to investigate the functional significance of CRC-derived migrasomes, particularly under hypoxic conditions, in promoting liver metastasis and modulating the tumor immune microenvironment. Migrasomes in CRC tissues and cells were characterized using transmission electron microscopy or immunofluorescence. A mouse liver metastasis model and single-cell RNA sequencing (scRNA-seq) were employed to explore functional outcomes and cellular interactions. Migrasome structures were observed in both primary CRC and metastatic liver tissues, and live-cell imaging revealed hypoxic CRC cells released increased numbers of migrasomes. In vivo imaging demonstrated hepatic accumulation of hypoxic migrasomes and enhanced liver metastasis in mice. ScRNA-seq of liver metastases revealed that hypoxic migrasomes reprogrammed the tumor microenvironment, notably expanding a Tmem45a⁺ fibroblast subset with myofibroblast features and promoting CD5L⁺ macrophage differentiation with elevated efferocytic capacity. Mechanistically, NRP2, enriched in migrasomes derived from hypoxic CRC cells, was transferred to macrophages, binding with PROX1 to drive CD5L expression and upregulate of efferocytosis receptors. NRP2 knockdown in CRC cells abrogated migrasome-induced CD5L⁺ macrophage polarization and impaired apoptotic tumor cell clearance. These findings demonstrate that hypoxic CRC-derived migrasomes facilitate liver metastasis by reprogramming stromal and immune compartments, particularly through NRP2/PROX1-mediated education of macrophages toward a pro-efferocytic CD5L⁺ phenotype. Our study reveals a previously unrecognized intercellular communication axis involving migrasomes in CRC progression and provides a potential therapeutic target for metastatic disease.

Environmental water contamination, particularly by heavy metal ions, has emerged as a worldwide concern due to their non-biodegradable nature and propensity to accumulate in soil and living organisms, posing a significant risk to human health. Therefore, the effective removal of heavy metal ions from wastewater is of utmost importance for both public health and environmental sustainability. In this study, we propose and design a membrane consisting of fluorographene (F-GRA) nanochannels to investigate its heavy metal ion removal capacity through molecular dynamics simulation. Although many previous studies have revealed the good performance of lamellar graphene membranes for desalination, how the zero-charged graphene functionalized by fluorine atoms (fully covered by negative charges) affects the heavy metal ion removal capacity is still unknown. Our F-GRA membrane exhibits an exceptional water permeability accompanied by an ideal heavy metal ion rejection rate. The superior performance of F-GRA membrane in removing heavy metal ions can be attributed to the negative charge of the F-GRA surface, which results in electrostatic attraction to positively charged ions that facilitates the optimal ion capture. Our analysis of the potential of mean force further reveals that water molecule exhibits the lowest free energy barrier relative to ions when passing through the F-GRA channel, indicating that water transport is energetically more favorable than ion. Additional simulations of lamellar graphene membranes show that graphene membranes have higher water permeabilities compared with F-GRA membranes, while robustly compromising the heavy meal ion rejection rates, and thus F-GRA membranes show better performances. Overall, our theoretical research offers a potential design approach of F-GRA membrane for heavy metal ions removal in future industrial wastewater treatment.

Graphene quantum dots (GQDs) have garnered significant attention, particularly in the biomedical domain. However, extensive research reveals a dichotomy concerning the potential toxicity of GQDs, presenting contrasting outcomes. Therefore, a comprehensive understanding of GQD biosafety necessitates a detailed supplementation of their toxicity profile. In this study, employing a molecular dynamics (MD) simulation approach, we systematically investigate the potential toxicity of GQDs on the CYP3A4 enzyme. We construct two distinct simulation systems, wherein a CYP3A4 protein is enveloped by either GQDs or GOQDs (graphene oxide quantum dots). Our results elucidate that GQDs come into direct contact with the bottleneck residues of Channels 2a and 2b of CYP3A4. Furthermore, GQDs entirely cover the exits of Channels 2a and 2b, implying a significant hindrance posed by GQDs to these channels and consequently leading to toxicity towards CYP3A4. In-depth analysis reveals that the adsorption of GQDs to the exits of Channels 2a and 2b is driven by a synergistic interplay of hydrophobic and van der Waals (vdW) interactions. In contrast, GOQDs only partially obstruct Channel 1 of CYP3A4, indicating a weaker influence on CYP3A4 compared to GQDs. Our findings underscore the potential deleterious impact of GQDs on the CYP3A4 enzyme, providing crucial molecular insights into GQD toxicology.

Graphene quantum dots (GQDs) have attracted significant attention across various scientific research areas due to their exceptional properties. However, studies on the potential toxicity of GQDs have yielded conflicting results. Therefore, a comprehensive evaluation of the toxicity profile of GQDs is essential for a thorough understanding of their biosafety. In this work, employing a molecular dynamics (MD) simulation approach, we investigate the interactions between GQDs and graphene oxide quantum dots (GOQDs) with the AQP1 water channel protein, aiming to explore the potential biological influence of GQDs/GOQDs. Our MD simulation results reveal that GQDs can adsorb to the loop region around the openings of AQP1 water channels, resulting in the blockage of these channels and potential toxicity. Interestingly, this blockage is concentration-dependent, with higher GQD concentrations leading to a greater likelihood of blockage. Additionally, GOQDs show a lower probability of blocking the openings of AQP1 water channels compared to GQDs, due to the hydrophobicity of the loop regions around the openings, which ultimately leads to lower interaction energy. Therefore, these findings provide new insights into the potential adverse impact of GQDs on AQP1 water channels through the blockage of their openings, offering valuable molecular insights into the toxicity profile of GQD nanomaterials.

Numerous reports have highlighted distinct clinical and biological characteristics between right-sided and left-sided colon cancers. Despite this research on commonalities and divergences among colorectal cancers (CRC) at different locations remain sparse. In order to elucidate gene expression disparities across various intestinal regions in CRC, we sourced several data series from the Gene Expression Omnibus (GEO) database. We isolated 344 tumor and 54 normal cases spanning seven locations: sigmoid, ascending, caecum, rectum, transverse, descending, and recto-sigmoid. Cell biological functions were assessed utilizing CCK8, EdU assays, Transwell assays, and wound healing assays. We identified location-related differentially expressed genes (DEGs) and their functional enrichment. TNFSF4 exhibited variances between the transverse and descending regions, allowing for discrimination of tumor tissues across four locations (sigmoid, ascending, caecum, and descending) via immune cells. Moreover, we identified 16 hub genes that collectively indicate commonality among the seven different tissue origins. Furthermore, 6 location-related genes, including DCBLD2, GTF3A, GSS, PDK1, TEAD3 and EGR2 were identified for targeted interventions. In vitro experiments indicated that increased GZMB and decreased IER3 reduced CRC cell proliferation, migration, and invasion. In summary, 16 hub genes and 6 location-related genes enhance our understanding of the potential molecular mechanisms underlying CRC spatial heterogeneity. Furthermore, GZMB and IER3 might be potential targets for CRC therapy.

Graphene quantum dots (GQDs) have garnered significant attention across numerous fields due to their ultrasmall size and exceptional properties. However, their extensive applications may lead to environmental exposure and subsequent uptake by humans. Yet, conflicting reports exist regarding the potential toxicity of GQDs based on experimental investigations. Therefore, a comprehensive understanding of GQD biosafety requires further microscopic and molecular-level investigations. In this study, we employed molecular dynamics (MD) simulations to explore the interactions between GQDs and graphene oxide quantum dots (GOQDs) with a protein model, the human intestinal fatty acid binding protein (HIFABP), that plays a crucial role in mediating the carrier of fatty acids in the intestine. Our MD simulation results reveal that GQDs can be adsorbed on the opening of HIFABP, which serves as an entrance for the fatty acid molecules into the protein’s interior cavity. This adsorption has the potential to obstruct the opening of HIFABP, leading to the loss of its normal biological function and ultimately resulting in toxicity. The adsorption of GQDs is driven by a combination of van der Waals (vdW), π-π stacking, cation-π, and hydrophobic interactions. Similarly, GOQDs also exhibit the ability to block the opening of HIFABP, thereby potentially causing toxicity. The blockage of GOQDs to HIFABP is guided by a combination of vdW, Coulomb, π-π stacking, and hydrophobic interactions. These findings not only highlight the potential harmful effects of GQDs on HIFABP but also elucidate the underlying molecular mechanism, which provides crucial insights into GQD toxicology.

Two-dimensional (2D) metal-organic frameworks (MOFs) have been extensively utilized across various research areas. However, the application of 2D MOF-based membranes for the removal of heavy metal ions remains largely unexplored, despite their potential as suitable candidates due to their inherent porosity. In this study, we employed molecular dynamics (MD) simulations to investigate the capacity of a typical 2D MOF, Cu-THQ, for the separation of heavy metal ions, including Cd²⁺, Cu²⁺, Hg²⁺, and Pb²⁺. Our MD results demonstrate that single-layered Cu-THQ MOF membranes exhibit excellent performance in heavy metal ion removal, with nearly 100% ion rejection while also allowing high water permeability. Free energy calculations confirm that water transport through the Cu-THQ membrane is energetically more favorable compared to the transport of heavy metal ions. Further simulations of multilayered Cu-THQ membranes indicate that increasing the number of Cu-THQ MOF layers hinders water molecule transport, resulting in a reduction in water permeability due to a more widespread adsorption, that is primarily driven by electrostatic interactions within the membrane pores. Therefore, our simulations not only identify a promising MOF membrane candidate for efficient heavy metal ion removal but also suggest an optimal MOF construction scheme, which provide beneficial information for future applications in the sieving field.