Based on scRNA-seq and bulk RNA-seq to establish tumor immune microenvironment-associated signature of skin melanoma and predict immunotherapy response.

Skin cutaneous melanoma (SKCM), a form of skin cancer, ranks among the most formidable and lethal malignancies. Exploring tumor microenvironment (TME)-based prognostic indicators would help improve the efficacy of immunotherapy for SKCM patients. This study analyzed SKCM scRNA-seq data to cluster non-malignant cells that could be used to explore the TME into nine immune/stromal cell types, including B cells, CD4 T cells, CD8 T cells, dendritic cells, endothelial cells, Fibroblasts, macrophages, neurons, and natural killer (NK) cells. Using data from The Cancer Genome Atlas (TCGA), we employed SKCM expression profiling to identify differentially expressed immune-associated genes (DEIAGs), which were then incorporated into weighted gene co-expression network analysis (WGCNA) to investigate TME-associated hub genes. Discover candidate small molecule drugs based on pivotal genes. Tumor immune microenvironment-associated genes (TIMAGs) for constructing TIMAS were identified and validated. Finally, the characteristics of TIAMS subgroups and the ability of TIMAS to predict immunotherapy outcomes were analyzed. We identified five TIMAGs (CD86, CD80, SEMA4D, C1QA, and IRF1) and used them to construct TIMAS. In addition, five potential SKCM drugs were identified. The results showed that TIMAS-low patients were associated with immune-related signaling pathways, high MUC16 mutation frequency, high T cell infiltration, and M1 macrophages, and were more favorable for immunotherapy. Collectively, TIMAS constructed by comprehensive analysis of scRNA-seq and bulk RNA-seq data is a promising marker for predicting ICI treatment outcomes and improving individualized therapy for SKCM patients.

Ranitidine as an adjuvant regulates macrophage polarization and activates CTLs through the PI3K-Akt2 signaling pathway.

Adjuvants are an indispensable component of vaccines, but there are few adjuvants for human vaccines. H2 receptor blockers, inhibiting gastric acid secretion, have immune enhancement effects. Ranitidine (RAN) is a water-soluble H2 receptor blocker, and whether it has an immune-enhancing effect is still unknown. In this study, flow cytometry, western blotting, and immunofluorescence methods were used to analyze whether RAN could activate macrophage polarization to the M1 phenotype in vivo and in vitro. Here, we found that the M1 inflammatory cytokine levels and surface markers in RAW264.7 cells were upregulated by NF-κB activation, possibly through the PI3K-Akt2 signaling pathway, after RAN treatment. Endocytic function was also enhanced by feedback regulation of Akt2/GSK3ß/Dynmin1 signaling. Furthermore, to evaluate the adjuvant function of RAN, we used OVA plus RAN as a vaccine to inhibit the growth of B16-OVA tumors in mice. We also found that in the RAN adjuvant group, macrophage polarization to M1, Th1 cell differentiation, and cytotoxic T lymphocyte (CTL) activation were significantly upregulated. The tumor growth of mice was inhibited, and the survival rate of mice was significantly improved. This study provides new evidence for the mechanism by which RAN activates the immune response and is expected to provide a new strategy for the research and development of tumor vaccine adjuvants.

Rhombohedral/Cubic In2O3 Phase Junction Hybridized with Polymeric Carbon Nitride for Photodegradation of Organic Pollutants.

In recent studies, phase junctions constructed as photocatalysts have been found to possess great prospects for organic degradation with visible light. In this study, we designed an elaborate rhombohedral corundum/cubic In2O3 phase junction (named MIO) combined with polymeric carbon nitride (PCN) via an in situ calcination method. The performance of the MIO/PCN composites was measured by photodegradation of Rhodamine B under LED light (λ = 420 nm) irradiation. The excellent performance of MIO/PCN could be attributed to the intimate interface contact between MIO and PCN, which provides a reliable charge transmission channel, thereby improving the separation efficiency of charge carriers. Photocatalytic degradation experiments with different quenchers were also executed. The results suggest that the superoxide anion radicals (O2-) and hydroxyl radicals (·OH) played the main roles in the reaction, as opposed to the other scavengers. Moreover, the stability of the MIO/PCN composites was particularly good in the four cycling photocatalytic reactions. This work illustrates that MOF-modified materials have great potential for solving environmental pollution without creating secondary pollution.

Baicalein inhibits the polarization of microglia/macrophages to the M1 phenotype by targeting STAT1 in EAE mice.

Microglia/macrophage polarization modulation plays a key role in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). M1 microglia/macrophages secrete a variety of cytokines that cause inflammation and facilitate demyelination in the central nervous system (CNS). Baicalein (5,6,7-trihydroxyflavone, C15H10O5, BAI), a natural flavonoid isolated from the roots of the traditional Chinese medicine Scutellaria baicalensis Georgi, has been suggested to have a wide range of biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. In this study, flow cytometry, Western blotting, immunofluorescence and other methods were used to investigate whether BAI could reduce the demyelination and inflammatory response of the spinal cord in EAE mice induced by MOG35-55 and affect the polarization of spinal microglia/macrophages. Our results showed that BAI treatment delayed the onset of EAE and alleviated clinical symptoms, demyelination and inflammatory cell infiltration. Meanwhile, BAI inhibited the overactivation of M1 microglia/macrophages in vivo and in vitro, significantly decreased the expression of proinflammatory cytokines in M1 microglia/macrophages, and inhibited the activation of STAT1. Subsequently, molecular docking, pull-down and immunofluorescence experiments confirmed that BAI has the ability to bind to the SH2 domain of STAT1 and that BAI colocalizes with p-STAT1 in the cytoplasm rather than being transferred to the nucleus during inflammatory stimulation. This study showed that BAI might inhibit the polarization of microglia/macrophages to the M1 phenotype in EAE mice by targeting STAT1. This new discovery lays a theoretical and experimental foundation for the clinical application of BAI in the treatment of MS.

Low Expression Levels of CXCL12, CXCR4, and CXCR 7 in Peripheral Blood and Decidual Tissues are Associated with Miscarriage in Women.

Miscarriage can cause significant physical and psychological harm to women. The stromal cell-derived factor 1 (SDF-1, also known as CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) and C-X-C motif chemokine receptor 7 (CXCR7) axis can promote the proliferation and invasion of trophoblast cells in early pregnancy, and maintain immune tolerance at the maternal-fetal interface to aid with pregnancy success. From our findings, the serum CXCL12 level of women who have miscarried (n = 25) was significantly lower than that of healthy early pregnancy women (n = 20) by ELISA (P < .001). Additionally, CXCL12 levels in normal non-pregnant women (n = 20) were significantly lower than those in early pregnancy women (P < .001) and women who have miscarried (P < .001). Quantitative real-time PCR detected no significant difference in the mRNA transcription levels of CXCR4 and CXCR7 in the decidua tissues of women with early pregnancy (n = 20) and miscarriage (n = 20) (P = .724, P = .281, respectively). However, Western blot and immunohistochemistry of CXCR4 and CXCR7 in decidual tissue of women who have miscarried (n = 20) were significantly lower than those in early pregnancy women (n = 20) (P < .05 for both). Therefore, we believe that the increased serum CXCL12 levels in pregnant offspring may benefit normal pregnancy maintenance. The low level of CXCL12 in peripheral blood and the low expression of CXCR4 and CXCR7 proteins in decidua may be associated with the occurrence of early spontaneous abortion, and the clinical application value of serum CXCL12 in predicting adverse pregnancy outcomes is worth further exploring.

Tunable Carrier Transfer of Polymeric Carbon Nitride with Charge-Conducting CoV2O6∙2H2O for Photocatalytic O2 Evolution.

Photocatalytic water splitting is one of the promising approaches to solving environmental problems and energy crises. However, the sluggish 4e- transfer kinetics in water oxidation half-reaction restricts the 2e- reduction efficiency in photocatalytic water splitting. Herein, cobalt vanadate-decorated polymeric carbon nitride (named CoVO/PCN) was constructed to mediate the carrier kinetic process in a photocatalytic water oxidation reaction (WOR). The photocatalysts were well-characterized by various physicochemical techniques such as XRD, FT-IR, TEM, and XPS. Under UV and visible light irradiation, the O2 evolution rate of optimized 3 wt% CoVO/PCN reached 467 and 200 µmol h-1 g-1, which were about 6.5 and 5.9 times higher than that of PCN, respectively. Electrochemical tests and PL results reveal that the recombination of photogenerated carriers on PCN is effectively suppressed and the kinetics of WOR is significantly enhanced after CoVO introduction. This work highlights key features of the tuning carrier kinetics of PCN using charge-conducting materials, which should be the basis for the further development of photocatalytic O2 reactions.

Chrysin enhances antitumour immunity response through the IL-12-STAT4 signal pathway in the B16F10 melanoma mouse model.

Chrysin (CHR) is a flavonoid with extensive pharmacological activity. The molecular formula of CHR is C15 H10 O4 . CHR is reported to have antioxidative, antitumour and antiviral functions. To evaluate its potential function as a vaccine adjuvant, we prepared a melanoma vaccine using a soluble protein extract of B16F10 melanoma cells as antigen and CHR as an adjuvant. The melanoma model was developed after two immunizations, and it was discovered that combining B16F10 soluble protein antigen-mixed CHR vaccine could inhibit tumour growth in the mouse model, and the overall survival rate was higher than that of the B16F10 antigen vaccine alone. In vivo and in vitro experiments were conducted to determine whether CHR functioned as an adjuvant by activating antigen-presenting cells (APCs). We discovered that CHR activated APCs both in vivo and in vitro and may enhance Th1 cell function by activating the IL12-STAT4 signal pathway, thereby enhancing the antitumour response of cytotoxic T lymphocytes (CTLs) in vivo. Next, to verify the critical role of CD8+ T cells in suppressing melanoma development, we transplanted CD8+ T cells from immunized mice to B16F10 tumour-bearing mice and discovered that the survival rate of tumour-bearing mice was significantly prolonged. In summary, our experimental results indicate that CHR can be used as a potential adjuvant to enhance antigen immunogenicity, inhibit B16F10 tumour growth in mice and improve tumour immune response.

Enhanced Oil Recovery by a Suspension of Core-Shell Polymeric Nanoparticles in Heterogeneous Low-Permeability Oil Reservoirs.

Polymeric nanoparticle suspension is a newly developed oil-displacing agent for enhanced oil recovery (EOR) in low-permeability reservoirs. In this work, SiO2/P(MBAAm-co-AM) polymeric nanoparticles were successfully synthesized by a simple distillation-precipitation polymerization method. Due to the introduction of polymer, the SiO2/P(MBAAm-co-AM) nanoparticles show a favorable swelling performance in aqueous solution, and their particle sizes increase from 631 to 1258 nm as the swelling times increase from 24 to 120 h. The apparent viscosity of SiO2/P(MBAAm-co-AM) suspension increases with an increase of mass concentration and swelling time, whereas it decreases as the salinity and temperature increase. The SiO2/P(MBAAm-co-AM) suspension behaves like a non-Newtonian fluid at lower shear rates, yet like a Newtonian fluid at shear rates greater than 300 s-1. The EOR tests of the SiO2/P(MBAAm-co-AM) suspension in heterogeneous, low-permeability cores show that SiO2/P(MBAAm-co-AM) nanoparticles can effectively improve the sweep efficiency and recover more residual oils. A high permeability ratio can result in a high incremental oil recovery in parallel cores. With an increase of the permeability ratio of parallel cores from 1.40 to 15.49, the ratios of incremental oil recoveries (low permeability/high permeability) change from 7.69/4.61 to 23.61/8.46. This work demonstrates that this SiO2/P(MBAAm-co-AM) suspension is an excellent conformance control agent for EOR in heterogeneous, low-permeability reservoirs. The findings of this study can help to further the understanding of the mechanisms of EOR using SiO2/P(MBAAm-co-AM) suspension in heterogeneous, low-permeability reservoirs.

Role of LPSO Phase in Crack Propagation Behavior of an As-Cast Mg-Y-Zn Alloy Subjected to Dynamic Loadings.

In this work, the role of long period stacking ordered (LPSO) phase in the crack propagation behavior of an as-cast Mg95.5Y3Zn1.5 alloy was investigated by dynamic four-point bent tests. The as-cast Mg95.5Y3Zn1.5 alloy is mainly composed of Mg matrix, 18R LPSO phase located at the grain boundaries and 14H LPSO phase located within the Mg matrix. The alloy exhibits excellent dynamic mechanical properties; the yield stress, maximum stress and strain to failure are 190.51 ± 3.52 MPa, 378.32 ± 4.26 MPa and 0.168 ± 0.006, respectively, at the strain rate of ~3000 s-1. The LPSO phase effectively hinders dynamic crack propagation in four typical ways, including crack tip blunting, crack opening inhibition, crack deflection and crack bridging, which are beneficial to the mechanical properties of the alloy under dynamic loadings.

From Silver Nanoflakes to Silver Nanonets: An Effective Trade-Off between Conductivity and Stretchability of Flexible Electrodes.

Flexible and stretchable conductive materials have received significant attention due to their numerous potential applications in flexible printed electronics. In this paper, we describe a new type of conductive filler for flexible electrodes-silver nanonets prepared through the "dissolution-recrystallization" solvothermal route from porous silver nanoflakes. These new silver fillers show characteristics of both nanoflakes and nanoparticles with propensity to form interpenetrating polymer-silver networks. This effectively minimizes trade-off between composite electrode conductivity and stretchability and enables fabrication of the flexible electrodes simultaneously exhibiting high conductivity and mechanical durability. For example, an electrode with uniform, networked silver structure from the flakiest silver particles showed the lowest increase of resistivity upon extension (3500%), compared to that of the electrode filled with less flaky (3D) particles (>50,000%).

Construction of fiber-shaped silver oxide/tantalum nitride p-n heterojunctions as highly efficient visible-light-driven photocatalysts.

Constructing novel and efficient p-n heterojunction photocatalysts has stimulated great interest. Herein, we report the design and synthesis of fiber-shaped Ag2O/Ta3N5p-n heterojunctions as a kind of efficient photocatalysts. Ta3N5 nanofibers were prepared by an electrospinning-calcination-nitridation method, and then the in-situ anchoring of Ag2O on their surfaces was realized by a facile deposition method. The resulting Ag2O/Ta3N5 heterojunctions were comprised of porous Ta3N5 nanofibers (diameter: ∼150nm) and Ag2O nanoparticles (size: ∼12nm). The photocatalytic activity of these heterojunctions were studied by decomposing rhodamine B (RhB) dye and tetracycline (TC) antibiotic under visible light (λ>400nm). In all the samples, the heterojunction with Ag2O/Ta3N5 molar ratio of 0.2/1 displays the best activity. It is found that a synergistic effect contributes to the effective suppression of charges recombination between Ta3N5 and Ag2O, leading to an enhanced photocatalytic activity with good stability. The photogenerated holes (h+) and superoxide radicals (O2-) play dominant roles in the photocatalytic process. These p-n heterojunctions will have great potential for environmental remediation because of the facile preparation process and exceptional photocatalytic activity.

Influence of biocorrosion on microstructure and mechanical properties of deformed Mg-Y-Er-Zn biomaterial containing 18R-LPSO phase.

The microstructure and mechanical properties of as-extruded Mg-8Y-1Er-2Zn (wt%) alloy containing long period stacking ordered (LPSO) phase are comparatively investigated before and after corrosion in a simulated body fluid (SBF) at 37°C. The as-extruded alloy consists of a long strip-like 18R-LPSO phase and some fine lamellae grains formed by primary recrystallization during the extrusion process. The hydrogen evolution volume per day fluctuates between 0.21 and 0.32ml/cm(2) in the immersion test for 240h, and the corresponding corrosion rate is calculated as 0.568mm/y. The corrosion product is determined as Mg(OH)2, whilst a Ca(H2PO4)2 compound is also observed on the surface of the samples. The corrosion site preferentially occurs at the interface between LPSO phase and Mg matrix. Before immersing, the tensile yield strength (TYS), ultimate tensile strength (UTS) and elongation of the alloy are 275MPa, 359MPa, and 19%, respectively. More attractively, these mechanical properties can be maintained even after immersing in SBF for 240h (TYS, UTS and elongation are 216MPa, 286MPa and 6.8%, respectively) because of the existence of high anti-corrosion LPSO phase.