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We previously showed that ubiquitous overexpression of the chromatin remodeling factor SWItch3-related gene (SRG3) promotes M2 macrophage differentiation, resulting in anti-inflammatory responses in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Since hepatic macrophages are responsible for sepsis-induced liver injury, we investigated herein the capacity of transgenic SRG3 overexpression (SRG3β-actin mice) to modulate sepsis in mice exposed to lipopolysaccharide (LPS) plus d-galactosamine (d-GalN). Our results demonstrated that ubiquitous SRG3 overexpression significantly protects mice from LPS/d-GalN-induced lethality mediated by hepatic M1 macrophages. These protective effects of SRG3 overexpression correlated with the phenotypic conversion of hepatic macrophages from an M1 toward an M2 phenotype. Furthermore, SRG3β-actin mice had decreased numbers and activation of natural killer (NK) cells but not natural killer T (NKT) cells in the liver during sepsis, indicating that SRG3 overexpression might contribute to cross-talk between NK cells and macrophages in the liver. Finally, we demonstrated that NKT cell-deficient CD1d KO/SRG3β-actin mice are protected from LPS/d-GalN-induced sepsis, indicating that NKT cells are dispensable for SRG3-mediated sepsis suppression. Taken together, our findings provide strong evidence that SRG3 overexpression may serve as a therapeutic approach to control overwhelming inflammatory diseases such as sepsis.

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

Sintering of multiple single-crystal titanium (Ti) nanoparticles (NPs) during additive manufacturing by using ultrafast laser was simulated using molecular dynamics (MD). The aim was to better understand how factors such as sintering temperature and heating rate would influence the mechanical properties of the ultrafine-sized sintered products, i.e., Ti “NP-chains.” For this purpose, the effects of heating and strain rate on the tensile behavior of the final sintered products were studied in detail. Ti NP-chain precursors with weak neck connections were first created through solid-state sintering process at room temperature. They were later heated very rapidly to 800 K, 1200 K, or 1500 K with two different heating rates of 0.04 K/ps and 0.2 K/ps, and maintained at these high-temperature levels for 1 ns to mimic the fast temperature rise and short equilibration due to femtosecond/picosecond laser irradiation. The formed Ti NP-chains with different neck connection strengths were then cooled to 298 K. Those final NP-chains were subjected to uniaxial tension at three different strain rates of 0.001%/ps, 0.01%/ps, and 0.1%/ps. Our simulation results indicate a strong correlation between the tensile strength of the final NP-chain product and the heating rate during the previous short sintering process (including the ultrafast temperature rise and up to 1-ns high-temperature equilibration). A slower heating rate to a higher temperature level yields larger neck connection diameters in the final NP-chain product, resulting a higher tensile strength. Furthermore, our results demonstrate that high strain rates applied to the NP-chains with stronger neck connections result in an improvement in the tensile strength and ductility of the final products. In contrast, sintered products resulting from a lower temperature level show an elastic-brittle-damage behavior. Due to the weak neck connections and limited crystal sliding, the heating rate effect during sintering does not have a significant effect on the tensile strength.