Fibrosis is the extensive deposition of fibrous connective tissue, and it is characterized by the accumulation of collagen and other extracellular matrix (ECM) components. Fibrosis is essential for wound healing and tissue repair in response to a variety of triggers, which include infection, inflammation, autoimmune disorder, degenerative disease, tumor, and injury. Fibrotic remodeling in various diseases, such as liver cirrhosis, pulmonary fibrosis, renal interstitial fibrosis, myocardial infarction, systemic sclerosis (SSc), and graft-versus-host disease (GVHD), can impair organ function, causing high morbidity and mortality. Both innate and adaptive immunity are involved in fibrogenesis. Although the roles of macrophages in fibrogenesis have been studied for many years, the underlying mechanisms concerning the manner in which T cells regulate fibrosis are not completely understood. The T cell receptor (TCR) engages the antigen and shapes the repertoire of antigen-specific T cells. Based on the divergent expression of surface molecules and cell functions, T cells are subdivided into natural killer T (NKT) cells, γδ T cells, CD8 + cytotoxic T lymphocytes (CTL), regulatory T (Treg) cells, T follicular regulatory (Tfr) cells, and T helper cells, including Th1, Th2, Th9, Th17, Th22, and T follicular helper (Tfh) cells. In this review, we summarize the pro-fibrotic or anti-fibrotic roles and distinct mechanisms of different T cell subsets. On reviewing the literature, we conclude that the T cell regulations are commonly disease-specific and tissue-specific. Finally, we provide perspectives on microbiota, viral infection, and metabolism, and discuss the current advancements of technologies for identifying novel targets and developing immunotherapies for intervention in fibrosis and fibrotic diseases.

The future of fuel supply will undoubtedly involve the utilization of heavy crude oils, including those from nonconventional sources, such as bitumen and oil shale. Because of their dense nature and poor compositional characteristics, heavy oils cannot be admitted straightly as refinery feeds, since the direct processing of such oils hardly produces engine fuels of commercial standard. The currently available refinery setups also require substantial retrofitting in order to process such heavy feeds. Thus, heavy oils must undergo an initial upgrading called hydrotreatment (HDT) by which the feeds are converted to qualified fuel oils or synthetic crude (syncrude) for easy handling. Removing the considerable amount of sulfur (S) and nitrogen (N) compounds present in the heavy crude oils selectively by hydrodesulfurization (HDS) and hydrodenitrogenation (HDN), respectively, is among the most critical and challenging aspects of the upgrading. However, the mechanism of these two reactions, in relation to different catalytic sites, temperature, pressure, and other operation variables, is not fully understood or well-documented. By analyzing the possible reaction routes involved in S and N removal by HDT, this review sets to bridge the gap that has been left void for a long period of time, to serve as a guide for innovative heavy crude oil upgrading technologies. It finally reports the current challenges impeding the speedy inclusion of heavy crude oils into the global oil supply stream, and proffer perspective solutions together with future research trends.

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The intestinal flora plays an important role in the development of many human and animal diseases. Microbiome association studies revealed the potential regulatory function of intestinal bacteria in many liver diseases, such as autoimmune hepatitis, viral hepatitis and alcoholic hepatitis. However, the key intestinal bacterial strains that affect pathological liver injury and the underlying functional mechanisms remain unclear. We found that the gut microbiota from gentamycin (Gen)-treated mice significantly alleviated concanavalin A (ConA)-induced liver injury compared to vancomycin (Van)-treated mice by inhibiting CD95 expression on the surface of hepatocytes and reducing CD95/CD95L-mediated hepatocyte apoptosis. Through the combination of microbiota sequencing and correlation analysis, we isolated 5 strains with the highest relative abundance, Bacteroides acidifaciens (BA), Parabacteroides distasonis (PD), Bacteroides thetaiotaomicron (BT), Bacteroides dorei (BD) and Bacteroides uniformis (BU), from the feces of Gen-treated mice. Only BA played a protective role against ConA-induced liver injury. Further studies demonstrated that BA-reconstituted mice had reduced CD95/CD95L signaling, which was required for the decrease in the L-glutathione/glutathione (GSSG/GSH) ratio observed in the liver. BA-reconstituted mice were also more resistant to alcoholic liver injury. Our work showed that a specific murine intestinal bacterial strain, BA, ameliorated liver injury by reducing hepatocyte apoptosis in a CD95-dependent manner. Determination of the function of BA may provide an opportunity for its future use as a treatment for liver disease.

Supporting informationand the ORCID identification number(s) for the author(s) of this article can be found under: http://dx.

The filament fungal pathogen, Aspergillus flavus, spreads worldwide and contaminates several important crops. Histone posttranslational modifications are deeply involved in fungal development and virulence, but the biological function of the histone methyltransferase AflSet1 in A. flavus is still unknown. In the study, Aflset1 deletion strain was constructed through homologous recombination, and it was found that AflSet1 up-regulates hyphae growth, and promotes conidiation by sporulation regulation genes: abaA and brlA. It was also found that AflSet1 involves in sclerotia formation and AFB1 biosynthesis via sclerotia related transcriptional factors and orthodox AFB1 synthesis pathway, respectively. Crop models revealed that AflSet1 plays critical roles in colonization and AFB1 production on crop kernels. Lipase activity analysis suggested that AflSet1 affects fungal virulence to crops via digestive enzymes. Stresses tests revealed that AflSet1 is deeply involved in fungal resistance against osmotic, oxidative and cell membrane stress. The preparation of N_SET, SET domain deletion mutants and H988K mutant revealed that both domains play critical roles in fungal development and AFB1 production, and that H988 is very important in executing biological functions on morphogenesis and AFB1 synthesis. Subcellular location analysis revealed that AflSet1 is stably accumulated in nuclei in both spore germination and hyphae growth stages, even under the stress of SDS. Through immunoblot analysis, it was found that AflSet1 methylates H3K4me2 and me3 as well as H3K9me2. This study provides a solid evidence to discover the biological functions of histone methyltransferase in pathogenic fungi.

Solvothermal reactions of 5-phenylpyrimidine-2-thiol (5-phpymtH) with equimolar CuBr afforded one hexanuclear cluster [Cu(μ-5-phpymt)] (1) along with a tetranuclear by-product [{(CuBr)(μ-5-phpymtH)}(μ-5-phpymt)] (2). A two dimensional (2D) polymer [Cu(μ-5-phpymt)(μ-Br)] (3) was isolated from the reaction of 5-phpymtH with two equiv. of CuBr. Analogous reactions of 5-phpymtH with one or four equiv. of CuI produced one tetranuclear cluster [{Cu(μ-5-phpymtH)(μ-5-phpymt)}(μ-I)] (4) and one 2D polymer [CuI(μ-I)(μ-5-phpymt)] (5). Compound 1 possesses a water-wheel-shaped hexameric structure. Compound 2 has an H-shaped tetrameric structure. Compound 3 possesses a 2D network in which unique 1D [Cu(μ-Br)(μ-5-phpymt)] chains are connected by μ-Br ions. Compound 4 has another tetrameric structure in which two {Cu(μ-5-phpymtH)(μ-5-phpymt)} fragments are linked by a pair of μ-I ions. Compound 5 contains another 2D network in which hexanuclear {CuI(μ-I)} units are linked by μ-5-phpymt bridges. The 5-phpymt ligand shows four coordination modes: μ-κ(S)-κ(N) (4), μ-κ(S)-κ(N) (1 and 2), μ-κ(N)-κ(S)-κ(N') (5) and μ-κ(N)-κ(S)-κ(N') (3). Complex 1 shows strong solvatochromic behaviour and displays reversible luminescence switching upon alternate addition of CFCOOH and EtN into its CHCl solution. Complexes 1-5 exhibit a high photocatalytic activity towards the aerobic oxidative hydroxylation of arylboronic acids to phenols under visible light irradiation. Catalyst 5 can be reused in several cycles without any obvious decay of the catalytic efficiency. These results offer an interesting insight into how the CuX/5-phpymtH molar ratios and X ions exert great impacts on the coordination modes of the 5-phpymt ligand, the structures of the final complexes, and the luminescence and catalytic properties.

NAC (NAM, ATAF1/2, and CUC2) transcription factors are ubiquitously distributed in eukaryotes and play significant roles in stress response. However, the functional verifications of NACs in Picea (P.) wilsonii remain largely uncharacterized. Here, we identified the NAC transcription factor PwNAC11 as a mediator of drought stress, which was significantly upregulated in P. wilsonii under drought and abscisic acid (ABA) treatments. Yeast two-hybrid assays showed that both the full length and C-terminal of PwNAC11 had transcriptional activation activity and PwNAC11 protein cannot form a homodimer by itself. Subcellular observation demonstrated that PwNAC11 protein was located in nucleus. The overexpression of PwNAC11 in Arabidopsis obviously improved the tolerance to drought stress but delayed flowering time under nonstress conditions. The steady-state level of antioxidant enzymes’ activities and light energy conversion efficiency were significantly increased in PwNAC11 transgenic lines under dehydration compared to wild plants. PwNAC11 transgenic lines showed hypersensitivity to ABA and PwNAC11 activated the expression of the downstream gene ERD1 by binding to ABA-responsive elements (ABREs) instead of drought-responsive elements (DREs). Genetic evidence demonstrated that PwNAC11 physically interacted with an ABA-induced protein—ABRE Binding Factor3 (ABF3)—and promoted the activation of ERD1 promoter, which implied an ABA-dependent signaling cascade controlled by PwNAC11. In addition, qRT-PCR and yeast assays showed that an ABA-independent gene—DREB2A—was also probably involved in PwNAC11-mediated drought stress response. Taken together, our results provide the evidence that PwNAC11 plays a dominant role in plants positively responding to early drought stress and ABF3 and DREB2A synergistically regulate the expression of ERD1.