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Mesoporous MY-xGa zeolites exhibiting both crystallized pore walls and narrowly dispersed mesopores with different Ga content were successfully synthesized. The synthesized samples were characterized by XRD, N 2 adsorption desorption isotherms, SEM, TEM, XPS, FTIR, 29 Si MAS NMR, 71 Ga MAS NMR, and Py-FTIR methods. The results show that the synthesized samples exhibit unique open channel like mesopore systems and outstanding crystallite natures; no nonframework Ga species were observed over the MY-xGa series samples, and their acidic properties can be modulated by varying the Ga/Al ratio in the initial synthesis gel. The corresponding NiMo/HMY-xGa catalysts were prepared via the incipient wetness coimpregnation method; the morphologies of the sulfide catalysts were characterized by HRTEM, and the covalent states of the active metals were characterized by XPS. The catalytic activities of the investigated catalysts for the 4,6-DMDBT HDS reaction were assessed, and the collected products were analyzed by GC and GC-MS methods. The catalyst NiMo/HMY-0.5Ga showed the highest catalytic activity due to the synergistic effect of modulated acidic properties, excellent morphology, highest sulfidation degree, and proper proportion of NiMoS phase. More importantly, 4-MDBT, DBT, and BP were observed and identified as the products of the 4,6-DMDBT HDS reaction, designated as the demethylation pathway (DM) for the 4,6-DMDBT HDS reaction. Finally, a reaction network including DDS, HYD, ISO, and DM pathways for the 4,6-DMDBT HDS reaction over catalyst NiMo/HMY-0.5Ga was proposed.

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TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen The results indicated that TLR9-deficient mice were more susceptible to infection compared with wild-type and TLR2- or TLR4-deficient mice, as indicated by more severe intestinal damage and the highest bacterial load. TLR9 deficiency in intestinal epithelial cells (IECs) augmented the activation of NF-κB and NLRP3 inflammasomes significantly, resulting in increased secretion of IL-1β. IL-1β increased the expression of NKG2D on intestinal intraepithelial lymphocytes and NKG2D ligands on IECs, resulting in higher susceptibility of IECs to cytotoxicity of intestinal intraepithelial lymphocytes and damage to the epithelial barrier. We proposed that TLR9 regulates the NF-κB-NLRP3-IL-1β pathway negatively in -induced NKG2D-mediated intestinal inflammation and plays a critical role in defense against infection and in the protection of intestinal integrity.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins, resulting from maladaptive wound healing responses to chronic liver injury. γδT cells are important in chronic liver injury pathogenesis and subsequent liver fibrosis; however, their role and underlying mechanisms are not fully understood. The present study aims to assess whether γδT cells contribute to liver fibrosis regression. Using a carbon tetrachloride (CCl4)-induced murine model of liver fibrosis in wild-type (WT) and γδT cell deficient (TCRδ−/−) mice, we demonstrated that γδT cells protected against liver fibrosis and exhibited strong cytotoxicity against activated hepatic stellate cells (HSCs). Further study show that chronic liver inflammation promoted hepatic γδT cells to express NKp46, which contribute to the direct killing of activated HSCs by γδT cells. Moreover, we identified that an IFNγ-producing γδT cell subset (γδT1) cells exhibited stronger cytotoxicity against activated HSCs than the IL-17-producing subset (γδT17) cells upon chronic liver injury. In addition, γδT cells promoted the anti-fibrotic ability of conventional natural killer (cNK) cells and liver-resident NK (lrNK) cells by enhancing their cytotoxicity against activated HSCs. The cell crosstalk between γδT and NK cells was shown to depend partly on co-stimulatory receptor 4-1BB (CD137) engagement. In conclusion, our data confirmed the protective effects of γδT cells, especially the γδT1 subset, by directly killing activated HSCs and increasing NK cell-mediated cytotoxicity against activated HSCs in CCl4-induced liver fibrosis, which suggest valuable therapeutic targets to treat liver fibrosis.

Increased systemic free fatty acids (FFA) impair insulin sensitivity. In obese and diabetic subjects, production of tumor necrosis factor-␣ (TNF-␣), a proinflammatory cytokine, is elevated. TNF-␣ has a variety of effects by inducing inflammation, decreasing glucose utilization, and stimulating adipocyte lipolysis to release FFA to plasma. High doses of nonsteroidal anti-inflammatory drug salicylates have long been recognized to lower blood FFA and glucose in humans, although the mechanisms are not fully understood. In this report, we show that sodium salicylate at therapeutic concentrations directly blocks TNF-␣-stimulated lipolysis and therefore inhibits FFA release from primary rat adipocytes. To elucidate the cellular basis of this action, we show that salicylate suppresses TNF-␣-induced extracellular signal-related kinase activation and intracellular cAMP elevation, two early events during the lipolysis response to TNF-␣. Furthermore, salicylate prevents the down-regulation of cyclic-nucleotide phosphodiesterase 3B, an enzyme responsible for cAMP hydrolysis. Perilipins coat intracellular lipid droplet surface by restricting lipase access to the triacylglycerol substrates. TNF-␣ down-regulates perilipin but promotes its phosphorylation during lipolysis stimulation; these actions are efficiently reversed by salicylate. Salicylate slightly reduces basal but completely inhibits TNF-␣-liberated lipase activity. In contrast, neither salicylate nor TNF-␣ alters the protein levels of hormone-sensitive lipase and adipose triglyceride lipase. In addition, sodium salicylate restricts basal lipolysis simulated by a high concentration of glucose and significantly diminishes the high glucose-enhanced lipolysis response to TNF-␣. These results provide novel evidence that salicylate directly blocks TNF-␣-mediated FFA efflux from adipocytes, hence reducing plasma FFA levels and increasing insulin sensitivity.

If a painful procedure on neonates is inevitable, simple, convenient and effective pain-relief methods such as non-nutritive sucking or glucose solution can be provided alone. Based on a neonate's condition, nurses can provide 2 ml of 25% glucose solution through a syringe for a breastfeeding infant before an invasive procedure if nipple confusion is the concern.