Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis

Template-Mediated Synthesis of Hierarchically Porous Metal–Organic Frameworks for Efficient CO2/N2 Separation

Carbon dioxide (CO2) is generally unavoidable during the production of fuel gases such as hydrogen (H2) from steam reformation and syngas composed of carbon monoxide (CO) and hydrogen (H2). Efficient separation of CO2 from these gases is highly important to improve the energetic utilization efficiency and prevent poisoning during specific applications. Metal–organic frameworks (MOFs), featuring ordered porous frameworks, high surface areas and tunable pore structures, are emerging porous materials utilized as solid adsorbents for efficient CO2 capture and separation. Furthermore, the construction of hierarchical MOFs with micropores and mesopores could further promote the dynamic separation processes, accelerating the diffusion of gas flow and exposing more adsorptive pore surface. Herein, we report a simple, efficient, one-pot template-mediated strategy to fabricate a hierarchically porous CuBTC (CuBTC-Water, BTC = 1,3,5-benzenetricarboxylate) for CO2 separation, which demonstrates abundant mesopores and the superb dynamic separation ability of CO2/N2. Therefore, CuBTC-Water demonstrated a CO2 uptake of 180.529 cm3 g−1 at 273 K and 1 bar, and 94.147 cm3 g−1 at 298 K and 1 bar, with selectivity for CO2/N2 mixtures as high as 56.547 at 273 K, much higher than microporous CuBTC. This work opens up a novel avenue to facilely fabricate hierarchically porous MOFs through one-pot synthesis for efficient dynamic CO2 separation

Targeting Toll-like receptors against cancer

The discovery of Toll-like receptors (TLRs) about 20 years ago was a remarkable achievement not only in the field of immunology but also in the field of medicine. The TLRs are a family of pattern recognition receptors which play an important role in immune responses by recognizing pathogen-associated molecular patterns. The TLRs also recognize danger-associated molecular patterns, which are associated with some diseases such as cancer. Recent evidence shows that TLRs are expressed not only in immune cells but also in tumor cells. The TLRs appear to play a role in tumor progression and treatment. Most likely, TLR activation has an impact on the initiation, development and treatment of tumors by modulating the inflammatory microenvironment. However, the activation of TLRs contributes to both inhibition and promotion of various tumors, with unclear underlying mechanisms. In this review article, the authors elucidate their current understanding about the role of TLRs in tumor progression, as well as the recent progress in utilizing TLR agonists as potential therapeutic agents in cancer treatment

LHD3 Encoding a J-Domain Protein Controls Heading Date in Rice

Heading date is one of the most important agronomic traits of rice, which critically affects rice ecogeographical adaptation, yield and quality. In this study, a late heading date 3 (lhd3) mutant was screened from the 60Co-γ irradiation mutant library. The lhd3 delayed heading date in rice under both short day and long day conditions. Map-based cloning combined with Mutmap strategy was adopted to isolate the causal LHD3 gene. The LHD3 gene encodes a DNA_J domain protein, which was ubiquitously expressed in various plant organs, and dominant expressed in stems and leaves. Subcellular localization analysis showed that LHD3 was localized to nucleus, indicating that LHD3 may interact with other elements to regulate the expression of flowering genes. The transcriptions of the heading activators Ehd1, Hd3a and RFT1 significantly decreased in the lhd3 mutant, suggesting that LHD3 may control the heading date through the Ehd1-Hd3a/RFT1 photoperiodic flowering pathway. The variation and haplotype analyses of the genomic region of LHD3 showed that there were 7 haplotypes in the LHD3 region from 4 702 accessions. The haplotypes of LHD3 can be divided into two classes: class a and class b, and the heading dates of these two classes were significantly different. Further study showed that two single nucleotide polymorphisms (SNPs), SNP10 (G2100C) in Hap II and SNP3 (C861T) in Hap VII, may be the functional sites causing early and late heading in accessions. Nucleotide diversity analysis showed LHD3 had been selected in the indica population, rather than in the japonica population. Therefore, the present study sheds light on the regulation of LHD3 on heading date in rice and suggests that LHD3 is a novel promising new target for rice molecular design and breeding improvement

Tailoring Amine-Functionalized Ti-MOFs via a Mixed Ligands Strategy for High-Efficiency CO2 Capture

Amine-functionalized metal-organic frameworks (MOFs) are a promising strategy for the high-efficiency capture and separation of CO2. In this work, by tuning the ratio of 1,3,5-benzenetricarboxylic acid (H3BTC) to 5-aminoisophthalic acid (5-NH2-H2IPA), we designed and synthesized a series of amine-functionalized highly stable Ti-based MOFs (named MIP-207-NH2-n, in which n represents 15%, 25%, 50%, 60%, and 100%). The structural analysis shows that the original framework of MIP-207 in the MIP-207-NH2-n (n = 15%, 25%, and 50%) MOFs remains intact when the mole ratio of ligand H3BTC to 5-NH2-H2IPA is less than 1 to 1 in the resulting MOFs. By the introduction of amino groups, MIP-207-NH2-25% demonstrates outstanding CO2 capture performance up to 3.96 and 2.91 mmol g−1, 20.7% and 43.3% higher than those of unmodified MIP-207 at 0 and 25 °C, respectively. Furthermore, the breakthrough experiment indicates that the dynamic CO2 adsorption capacity and CO2/N2 separation factors of MIP-207-NH2-25% are increased by about 25% and 15%, respectively. This work provides an additional strategy to construct amine-functionalized MOFs with the maintenance of the original MOF structure and high performance of CO2 capture and separation

Analysis of Light Penetration Depth in Apple Tissues by Depth-Resolved Spatial-Frequency Domain Imaging

Spatial-frequency domain imaging (SFDI) has been developed as an emerging modality for detecting early-stage bruises of fruits, such as apples, due to its unique advantage of a depth-resolved imaging feature. This paper presents theoretical and experimental analyses to determine the light penetration depth in apple tissues under spatially modulated illumination. Simulation and practical experiments were then carried out to explore the maximum light penetration depths in ‘Golden Delicious’ apples. Then, apple experiments for early-stage bruise detection using the estimated reduced scattering coefficient mapping were conducted to validate the results of light penetration depths. The results showed that the simulations produced comparable or a little larger light penetration depth in apple tissues (~2.2 mm) than the practical experiment (~1.8 mm or ~2.3 mm). Apple peel further decreased the light penetration depth due to the high absorption properties of pigment contents. Apple bruises located beneath the surface peel with the depth of about 0–1.2 mm could be effectively detected by the SFDI technique. This study, to our knowledge, made the first effort to investigate the light penetration depth in apple tissues by SFDI, which would provide useful information for enhanced detection of early-stage apple bruising by selecting the appropriate spatial frequency

The Management of Autoimmune Hepatitis Patients with Decompensated Cirrhosis: Real-World Experience and a Comprehensive Review.

There is a paucity of information related to the usefulness of corticosteroid therapy in autoimmune hepatitis (AIH) with decompensated cirrhosis. In this study, we sought to determine the therapeutic effect of corticosteroids in this special group of AIH patients. Eighty-two AIH patients with decompensated cirrhosis were included through a retrospective analysis from January 2009 to September 2015. Sixty-four patients were treated with corticosteroids while 18 patients did not receive any corticosteroids. Clinical, laboratory, and histological characteristics and outcomes were analyzed comparing corticosteroid-treated and untreated groups. Patients that did not receive corticosteroids were older than corticosteroid-treated patients and had a worse survival. In corticosteroid-treated group, 40 of 64 patients reverted to compensated state and 15 patients remained decompensated, while 9 patients experienced liver-related death or transplantation. Patients who reverted to compensated state had significantly greater ALT, AST, GGT, white blood cell count, and platelet levels at presentation. Changes (Δ) in total bilirubin (TBIL) and MELD scores at day 7 after starting corticosteroid therapy revealed favorable predictive effects of treatment outcomes. Survival was significantly greater in patients with a ΔTBIL <-0.196 mg/dL (p = 0.001) 7 days after treatment. Infection was the most common cause of death or transplantation in the patients with treatment failure. Although it cannot be determined whether the results were due to the therapy or underlying patient characteristics, survival was greater in the corticosteroid-treated group with the benefit being greatest in patients with the greatest decrease in TBIL at day 7 after starting corticosteroid therapy

Blood samples were obtained from healthy controls (HC, n = 28), chronic hepatitis B (CHB, n = 18) and autoimmune hepatitis (AIH, n = 29) patients.

<p>Peripheral blood mononuclear cells (PBMCs) were isolated, labeled with fluorescent antibodies against CD4, CD25, CCR4 and CCR6, and analyzed by flow cytometry. (A) Plasma IL-17 and IL-23 levels. (B) Representative dot plots; and (C) Mean (±SD) percentage of Th17 (CD4⁺CD25⁻ CCR4⁺CCR6⁺) cells in PBMC. Panel B and C are gated on CD4⁺CD25⁻ cells. *p<0.05, **p<0.01.</p

Figure 4

<p>(A) IL-17 was added to HepG2 cell culture. IL-6 production by HepG2 cells in the media was measured by ELISA. (B) Total protein extract was made from HepG2 cells after stimulated with IL-17 (100 ng/ml). Western bolts were performed with antibodies specific against phosphorylated ERK1/2, p38 MAPK, JNK. The membranes were then stripped and re-probed with an antibody to total ERK, p38 MAPK and JNK. β-actin expression was determined as loading controls. (C) Specific inhibitors of MAPK signaling pathways (SB203580 for MAPK, PD98059 and U0126 for ERK, SP600125 for JNK, and DMSO as the carrier) were added to HepG2 cell culture before IL-17 stimulation. IL-6 in the media was measured by ELISA. (D) IL-17 was added to HepG2 cell culture. MCP-1 production by HepG2 cells in the media was measured by ELISA.</p