Search Results (12)

Cutaneous melanoma is an aggressive cancer with an increasing incidence worldwide, highlighting the need for research into its pathogenesis. The tumor microenvironment (TME) plays a critical role in melanoma progression and consists of cellular components and an extracellular matrix (ECM) rich in cytokines and signaling molecules. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs), which remodel the ECM and modulate immune responses. Among immune cells, tumor-associated macrophages (TAMs) predominate, and their polarization toward the M2 phenotype supports tumor progression. Tumor-infiltrating lymphocytes (TILs) have diverse functions, including cytotoxic T-cells, helper T-cells that modulate immune response, B-cells forming tertiary lymphoid structures (TLS), and regulatory T-cells with immunosuppressive properties. Dendritic cells (DCs) also play a complex role in the TME. A notable subpopulation are mature regulatory dendritic cells (mregDCs), which contribute to immune evasion. All of these TME components may drive tumorigenesis. Advancements in melanoma treatment—including immunotherapy and targeted therapies—have significantly improved outcomes in advanced-stage disease. In parallel, emerging approaches targeting the tumor microenvironment and gut microbiome, as well as personalized strategies such as neoantigen vaccines and cell-based therapies, are under active investigation and may further enhance therapeutic efficacy in the near future. Full article

The diversity of skin colors observed in reptiles is indicative of their adaptation to different ecological niches, with these color variations playing essential roles in survival and reproduction. The present study focused on two closely related species (Lycodon rufozonatus and Lycodon rosozonatus) within the Lycodon genus that exhibit the closest color and morphological similarities. We performed RNA sequencing on the scales of both species and obtained 350,346,591 and 331,537,523 clean reads, respectively. A comparative analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases revealed that the scales of the two species exhibited similar patterns of gene enrichment. Nevertheless, the results of the PCA and the t-SNE analysis demonstrated notable differences between the scales in the diverse color variations observed in the two species. Concurrently, we conducted a comparative analysis of the skin color-related genes and the differentially expressed genes, which revealed three genes exhibiting notable disparities: RU_DN1145_c3_g2 (mreg), RU_DN10511_c0_g1 (notch1), and Unigene11172 (notch1). In light of the aforementioned results, we hypothesize that the discrepancy in the scale color between the two species is attributable to alterations in specific gene loci and variations in expression levels. The data presented herein provide a molecular basis for future studies on the genetic and habitat adaptation functions of scale color differences in reptiles. Full article

The instance segmentation model based on deep learning has addressed the challenges in intelligently detecting water leakage in shield tunneling. Due to the limited generalization ability of the baseline model, occurrences of missed detections, false detections, and repeated detections are encountered during the actual detection of tunnel water leakage. This paper adopts Mask R-CNN as the baseline model and introduces a mask cascade strategy to enhance the quality of positive samples. Additionally, the backbone network in the model is replaced with RegNetX to enlarge the model’s receptive field, and MDConv is introduced to enhance the model’s feature extraction capability in the edge receptive field region. Building upon these improvements, the proposed model is named Cascade-MRegNetX. The backbone network MRegNetX features a symmetrical block structure, which, when combined with deformable convolutions, greatly assists in extracting edge features from corresponding regions. During the dataset preprocessing stage, we augment the dataset through image rotation and classification, thereby improving both the quality and quantity of samples. Finally, by leveraging pre-trained models through transfer learning, we enhance the robustness of the target model. This model can effectively extract features from water leakage areas of different scales or deformations. Through instance segmentation experiments conducted on a dataset comprising 766 images of tunnel water leakage, the experimental results demonstrate that the improved model achieves higher precision in tunnel water leakage mask detection. Through these enhancements, the detection effectiveness, feature extraction capability, and generalization ability of the baseline model are improved. The improved Cascade-MRegNetX model achieves respective improvements of 7.7%, 2.8%, and 10.4% in terms of AP, AP_0.5, and AP_0.75 compared to the existing Cascade Mask R-CNN model. Full article

In a group of Karachaevsky rams, a genome-wide associations analysis of single nucleotide polymorphisms (SNPs) with live parameters of meat production was performed. We used for genotyping the Ovine Infinium HD BeadChip 600 K, which consists of points to detection of 606,000 polymorphisms. A total of 12 SNPs was found to be significantly associated with live meat quality parameters of the corpus and legs and ultrasonic traits. In this case, 11 candidate genes were described, the polymorphic variants of which can change in sheep body parameters. We found SNPs in the exons, introns, and other regions of some genes and transcripts: CLVS1, EVC2, KIF13B, ENSOART00000000511.1, KCNH5, NEDD4, LUZP2, MREG, KRT20, KRT23 and FZD6. The described genes involved in the metabolic pathways of cell differentiation, proliferation and apoptosis are connected with the regulation of the gastrointestinal, immune and nervous systems. In known productivity genes (MSTN, MEF2B, FABP4, etc.), loci were not found to be a significant presence of influence on the meat productivity of the Karachaevsky sheep phenotypes. Our study confirms the possible involvement of the identified candidate genes in the formation of the phenotypes of productivity traits in sheep and indicates the need for new research into candidate genes structure in point to detect their polymorphisms. Full article

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated using a macrophage colony-stimulating factor with interferon (IFN)-γ. Herein, we generated Mregs with an elongated cell morphology from THP-1 cells that were stimulated with phorbol 12-myristate 13-acetate and cultured with both arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific markers, such as dehydrogenase/reductase 9, even when exposed to such inflammatory stimulants as IFN-γ, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti-inflammatory and anticoagulatory actions in response to xenogeneic cells, as well as exerting immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective. Full article

Regulatory macrophages (Mreg) are a special cell type that present a potential therapeutic strategy for various inflammatory diseases. In vitro, Mreg generation mainly takes 7–10 days of treatment with chemicals, including cytokines. In the present study, we established a new approach for Mreg generation using a three-dimensional (3D) micropatterned polydimethylsiloxane (PDMS) surface coated with a natural biopolymer adhesive polydopamine (PDA) and the common cell adhesion peptide motif arginylglycylaspartic acid (RGD). The 3D PDMS surfaces were fabricated by photolithography and soft lithography techniques and were subsequently coated with an RGD+PDA mixture to form a surface that facilitates cell adhesion. Human monocytes (THP-1 cells) were cultured on different types of 2D or 3D micropatterns for four days, and the cell morphology, elongation, and Mreg marker expression were assessed using microscopic and flow cytometric analyses. The cells grown on the PDA+RGD-coated 3D micropatterns (20-µm width/20-µm space) exhibited the most elongated morphology and strongest expression levels of Mreg markers, such as CD163, CD206, CD209, CD274, MER-TK, TREM2, and DHRS9. The present study demonstrated that PDA+RGD-coated 3D PDMS micropatterns successfully induced Mreg-like cells from THP-1 cells within four days without the use of cytokines, suggesting a time- and cost-effective method to generate Mreg-like cells in vitro. Full article

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn’s disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials. Full article

Colors are important phenotypic traits for fitness under natural conditions in vertebrates. Previous studies have reported several functional genes and genetic variations of pigmentation, but the formation mechanisms of various skin coloration remained ambiguous in fish. Jinbian carp, a common carp variant, displays two colors (yellow and black) in the skin, thus, it is a good model for investigating the genetic basis of pigmentation. In the present study, using the Jinbian carp as model, isobaric tags for relative and absolute quantification (ITRAQ) proteomics analysis was performed for yellow and black skin, respectively. The results showed that 467 differentially expressed proteins (DEPs) were identified between the yellow skin and the black skin. Similar to mammals, the up-regulated DEPs in black skin included UV excision repair protein RAD23 homolog A (Rad23a), melanoregulin (mreg), 5,6-dihydroxyindole-2-carboxylic acid oxidase5 (tyrp1) and melanocyte protein PMEL (PMEL), which were mainly grouped into melanogenesis pathway. However, several up-regulated DEPs in yellow skin were mainly enriched in nucleotide metabolism, such as GTPase IMAP family member 5 (GIMAP5), AMP deaminase 1 (AMPD1), adenosylhomocysteinase b (ahcy-b), and pyruvate kinase (PKM). In summary, several candidate proteins and their enrichment pathways for color variation in Jinbian carp were identified, which may be responsible for the formation of different colorations. Full article

Human mesenchymal stromal/stem cells (hMSCs) show great promise in cell therapy due to their immunomodulatory properties. The overall immunomodulatory response of hMSCs resembles the resolution of inflammation, in which lipid mediators and regulatory macrophages (Mregs) play key roles. We investigated the effect of hMSC cell-cell contact and secretome on macrophages polarized and activated toward Mreg phenotype. Moreover, we studied the effect of supplemented polyunsaturated fatty acids (PUFAs): docosahexaenoic acid (DHA) and arachidonic acid, the precursors of lipid mediators, on hMSC immunomodulation. Our results show that unlike hMSC cell-cell contact, the hMSC secretome markedly increased the CD206 expression in both Mreg-polarized and Mreg-activated macrophages. Moreover, the secretome enhanced the expression of programmed death-ligand 1 on Mreg-polarized macrophages and Mer receptor tyrosine kinase on Mreg-activated macrophages. Remarkably, these changes were translated into improved Candida albicans phagocytosis activity of macrophages. Taken together, these results demonstrate that the hMSC secretome promotes the immunoregulatory and proresolving phenotype of Mregs. Intriguingly, DHA supplementation to hMSCs resulted in a more potentiated immunomodulation with increased CD163 expression and decreased gene expression of matrix metalloproteinase 2 in Mreg-polarized macrophages. These findings highlight the potential of PUFA supplementations as an easy and safe method to improve the hMSC therapeutic potential. Full article

Forest fire modeling often requires estimates of fuel moisture status. Among the various fuel variables used for fire modeling studies, the 10-h fuel moisture content (10-h FMC) is a promising predictor since it can be automatically measured in real time at study sites, yielding more information for fire models. Here, the performance of 10-h FMC models based on three different approaches, including regression (M_REG), machine learning algorithms (M_ML) with random forest and support vector machine, and a process-based model (M_FSMM), were compared. In addition, whole-year models of each type were compared with their respective seasonal models to explore whether the development of separate seasonal models yielded better estimates. Meteorological conditions and 10-h FMC were measured each minute for 18 months in and near a forest site and used for constructing and examining the 10-h FMC models. In the assessments, M_ML showed the best performance (R² = 0.77–0.82 and root mean squared error [RMSE] = 2.05–2.84%). The introduction of the correction coefficient into M_REG improved its estimates (R² improved from 0.56–0.58 to 0.68–0.70 and RMSE improved from 3.13–3.85% to 2.64–3.27%) by reducing the errors associated with high 10-h FMC values. M_FSMM showed the worst performance (R² = 0.41–0.43 and RMSE = 3.70–4.39%), which could possibly be attributed to the lack of radiation input from the study sites as well as the particular fuel moisture stick sensor that was used. Whole-year models and seasonal models showed almost equal performance because 10-h FMC varied in response to atmospheric moisture conditions rather than specific seasonal patterns. The adoption of a hybrid modeling approach that blends machine-learning and process-based approaches may yield better predictability and interpretability. This study provides additional evidence of the lagged response of 10-h FMC after rainfall, and suggests a new way of accounting for this response in a regression model. Our approach using comparisons among models can be utilized for other fire modeling studies, including those involving fire danger ratings. Full article

Public health guidelines advise eating regular meals without defining “regular.” This study constructed a meaning for “regular” meals congruent with dietary quality. Parents of 4th grade youth in a school-based intervention (Clinicaltrials.gov NCT02491294) completed three, ASA24 online 24-h dietary recalls. Differences in time of intake across days for breakfasts, lunches, dinners were categorized with consistency denoted as always, often/sometimes or rarely/never and assigned values of 3, 2 or 1, respectively. Meal-specific values were summed to form mealtime regularity scores (mReg) ranging from 3 (low) to 9. Healthy eating index (HEI) scores were compared to mReg controlling for weekday/weekend recall pattern. Linear regression predicted HEI scores from mReg. Parents (n = 142) were non-Hispanic white (92%), female (88%) and educated (73%). One mReg version, mReg1 was significantly associated with total HEI, total fruit, whole fruit, tended to correlate with total protein, seafood/plant protein subcomponents. mReg1 predicted total HEI (p = 0.001) and was inversely related to BMI (p = 0.04). A score of three (always) was awarded to breakfasts, lunches or dinners with day-to-day differences of 0–60 min; also, lunches/dinners with one interval of 60–120 min when two meals were ≤60 min apart. More rigid mReg versions were not associated with dietary quality. Full article

Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals. Anti-GR1 administration immediately after Temoporfin-PDT of mouse SCCVII tumors abrogated curative effect of PDT. The opposite effect, increasing PDT-mediated tumor cure-rates was attained by delaying anti-GR1 treatment to 1 h post PDT. With PDT vaccines, multiple anti-GR1 administrations (days 0, 4, and 8 post vaccination) improved the therapy response with SCCVII tumors. The results with PDT suggest that neutrophils (boosting antitumor effect of this therapy) that are engaged immediately after photodynamic light treatment are within one hour replaced with a different myeloid population, presumably Mregs that hampers the therapy-mediated antitumor effect. Anti-GR1 antibody, when used with optimal timing, can improve the efficacy of both PDT of tumors in situ and PDT-generated cancer vaccines. Full article