In this study, the development of kinetic rate equations for catalytic methane chlorination over pellet-type catalysts was addressed. Experimental data at various temperatures, feed compositions, ...space velocities, and pressures were used to estimate the kinetic parameters. The average errors for methane conversion and methyl chloride (MCM) selectivity were 15.9 and 4.4%, respectively, validating the effectiveness of the developed kinetics. A process model was developed by considering a commercial-scale methane chlorination reactor and separation train. HCl, which was responsible for half of the chlorine gas in the feed, might reduce the economics of the process. The MeOH hydrochlorination reaction was combined with methane chlorination, and three variations of the combined process were suggested, depending on the configuration of the separation sequence. The MeOH hydrochlorination reduced the energy requirement by more than 80% compared to methane chlorination. Techno-economic analysis showed that the feeding of pure HCl had the lowest purchase and annual production costs, resulting in the lowest minimum selling price (MSP) of 0.90 $/kg-MCM. The sensitivity analysis of the MSP concerning the MeOH and HCl price showed that the proposed process is the most economical up to 1.8 $/kg-MeOH and 160 $/ton-HCl, respectively.
Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP in rheumatoid arthritis (RA) remains ...undefined. In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine the experimental phenotypes of RA. HRF/TCTP levels in the sera of RA patients were measured and compared to those from patients with osteoarthritis (OA), ankylosing spondylitis, Behçet's disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLSs) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLSs and CIA mice. Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels in the sera, synovial fluid, synovium, and FLSs were higher in patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with RA disease activity. The tumor-like aggressiveness of RA-FLSs was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice and had no detrimental effects in a murine tuberculosis model. Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.
Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact ...of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer. Moreover, LN-TRCs trans-present IL-2 to naive CD4+ T cells through CD25, thereby facilitating early IL-2-mediated signaling. CD25-deficient LN-TRCs exhibit attenuated STAT5 phosphorylation in naive CD4+ T cells during T cell differentiation, promoting T helper 17 (Th17) cell differentiation and Th17 response-related gene expression. In experimental autoimmune disease models, disease severity was elevated in mice lacking CD25 in LN-TRCs. Therefore, our results suggest that CD25 expression on LN-TRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring, naive CD4+ T cells, influencing the overall properties of immune responses.
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