Water oxidation is a critical process for electrochemical water splitting due to its inherent sluggish kinetics. In spite of the high catalytic activities of noble metal-based electrocatalysts for water oxidation, their high cost, rare reserves, and low stabilities drive researchers to exploit efficient but lowcost electrocatalysts. Ultrathin 2D nanomaterials are considered efficient electrocatalysts for oxygen evolution reaction (OER) in water splitting. Herein, a facile strategy is proposed to fabricate 2D FeNi layered double hydroxide (FeNi-LDH) nanosheets packed with the in situ produced 1D sword-like FeNi-MOFs by using FeNi-LDH as a semi-sacrificial template. In the composite, the thickness of the formed nanosheets is only 1.34 nm, much thinner than that of most previously reported 2D materials. The 1D porous sword-like MOF nanorods have a long length of around 1.3 µm. Due to the unique 2D/1D combined structure, the as-prepared FeNi LDH/MOF is directly used as electrocatalyst for the OER displays enhanced OER electrocatalytic performance with a low overpotential of 272 mV@100 mA cm -2 , a small Tafel slope of 34.1 mV dec -1 , high long-term durability. This work provides a new way to fabricate integrated ultrathin 2D nanosheets and MOFs as advanced catalysts for electrochemical energy conversion.

No abstract

No abstract

The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8 T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8 T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8 T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8 T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8 T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8 T cells but could significantly enhance IL-2-mediated promotion of CD8 T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8 T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4CD25 regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8 T cells, an effect suppressible by CD4CD25 Treg cells.

No abstract

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to infection and lack of effective treatment method. Supplementation of probiotics has emerged as a potential biotherapy for inflammatory diseases in recent years, but its role in protecting viscera against the damage caused by sepsis and the underlying mechanism is poorly understood. Streptococcus thermophilus 19 is one of the most well-studied probiotics, which is selected in this study among seven strains isolated from homemade yogurt due to its optimal ability of suppressing the inflammation response in vitro. It showed significant decrease in the expression of TNF-α, IL-1β, and IL-6 in the co-culture of S. thermophilus 19 and LPS-treated mouse macrophage. The effect of S. thermophilus 19 in mice and the response of mice gut microbiota were subsequently investigated. In LPS-induced septic mouse model, S. thermophilus 19 was highly resistant to LPS and exhibited significantly decreased expressions of inflammatory factors compared to LPS-treated mice. A MiSeq-based 16S rDNA sequence analysis revealed that the decrease of gut microbial diversity in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of S. thermophilus 19. Fusobacterium significantly decreased during the development of sepsis and rose again after supplement strain 19, while Flavonifractor showed the opposite trend, which demonstrated these two genera were the key bacteria that may function in the mice gut microbiota for alleviation of LPS-induced inflammation reaction. To conclude, S. thermophilus 19 may be a potential candidate for novel biotherapeutic interventions against inflammation caused by sepsis.

Keloid, a benign skin disorder, forms during wound healing in genetically susceptible individuals. To better control keloid and understand the molecular mechanisms, this study screened gene hypermethylations of GEO database microarray data on keloids and identified the hypermethylation of the secreted frizzled related protein-1 (SFRP1) promoter. Subsequently, hypermethylation and mRNA and protein levels were assessed in 57 cases of keloid vs. normal skin tissues. Fibroblasts from tissues were isolated for the assessment of gene regulation in vitro. The methods used were bioinformatic analysis, lentiviral infection carrying SFRP1 cDNA, qRT-PCR, western blot, immunohistochemistry, luciferase reporter assay, methylation-specific PCR and methylated DNA immunoprecipitation-qPCR, ELISA, and/or 5-Aza-2'-deoxycytidine treatment. The data revealed that the SFRP1 promoter was hypermethylated in keloid tissues, compared with that in normal skin tissues. The SFRP1 promoter methylation contributed to the downregulation of SFRP1 mRNA and protein in keloid tissues and keloid fibroblasts. The 5-Aza treatment significantly upregulated SFRP1 mRNA and protein level in keloid fibroblasts. Furthermore, the knockdown of DNMT1 expression, and not the expression of DNMT3a or DMNT3b, was responsible for the hypermethylation of the SFRP1 promoter and upregulation of SFRP1 mRNA and protein in keloid fibroblasts. In addition, the infection of lentivirus carrying SFRP1 cDNA significantly inhibited the signaling activity of Wnt/β-catenin and the mRNA and protein expression of β-catenin and α-SMA in keloid fibroblasts. In summary, the lost SFRP1 expression-induced Wnt/β-catenin signaling due to the hypermethylation of the SFRP1 promoter could associate with keloid development, suggesting that SFRP1 might be a therapeutic target for keloid treatment.

The severity of sepsis is associated with excessive inflammatory responses. MCP-1 induced protein (MCPIP1) could negatively regulate inflammatory responses by deubiquitinating K48 or K63 polyubiquitins of TNF receptor-associated factors. The function of MCPIP1 in negative regulation of inflammation is known, however, only the exact molecular pathway remains unknown. The aim of this study was to investigate whether and how MCPIP1 is involved in the regulation of lipopolysaccharides (LPS)-induced liver injury. Macrophages and a mouse model were induced by LPS treatment. Several in vitro assays, such as quantitative real-time PCR, immunoblotting, cell transfection, dual luciferase reporter assay, Enzyme-linked immunosorbent assay, and Hematoxylin-Eosin staining assay were used to explore the role of MCPIP1 and the interaction between MCPIP1, Sirtuin 1 (SIRT1), and microRNA-9 (miR-9). We found that the level of MCPIP1 increased and the level of SIRT1 decreased in LPS induced Kupffer cells or RAW 264.7 macrophages.Overexpression of MCPIP1 alleviated cytokine secretion and p65 nuclear translocation. Further study showed that MCPIP1 regulated p65 nuclear translocation by controlling p65 acetylation via promoting SIRT1 expression. Meanwhile, we found that miR-9 could directly regulate SIRT1 transcription by binding to the 3′-Untranslated Region of SIRT1 messenger RNA and that miR-9 was negatively regulated by MCPIP1. Importantly, overexpression of MCPIP1 in vivo could alleviate LPS-induced inflammation responses and liver injury in septic mice. These results demonstrated that MCPIP1 could alleviate inflammation responses and sepsis associated liver injury by promoting the expression of SIRT1, and miR-9 was involved in the MCPIP1-mediated regulation of SIRT1. Collectively, our results provide a possible novel signaling axis involving MCPIP1/miR-9/SIRT1 in LPS-induced septic mice. K E Y W O R D SMCP-1 induced protein (MCPIP1), microRNA-9, nuclear factor-kappa B (NF-κB), sepsis, sirtuin 1 (SIRT1)