GSDMA3 deficiency reprograms cellular metabolism and modulates BCR signaling in murine B cells.

Metabolism plays a crucial role in B cell differentiation and function. GSDMA3 is related to mitochondrial metabolism and is involved in immune responses. Here, we used Gsdma3 KO mice to examine the effect of GSDMA3 on B cells. The results demonstrated that GSDMA3 deficiency reprogrammed B cell metabolism, evidenced by upregulating PI3K-Akt-mTOR signaling, along with elevated ROS reproduction and reduced maximal oxygen consumption rate in mitochondria. Moreover, the BCR signaling in the KO B cells was impaired. The reduced BCR signaling was associated with decreased BCR clustering, caused by inhibited activation of WASP. However, GSDMA3 deficiency had no effects on B cell development and functions in humoral immunity, which might be associated with the compensation of upregulated GSDMA2 expression and the fine balance between PI3K signaling and BCR signals interaction. Our observations reveal a previously unknown influence of GSDMA3 on B cells under physiological and immunized states.

Abelson tyrosine kinase controls BCR signalling and B-cell differentiation by promoting B-cell metabolism.

As a nonreceptor tyrosine kinase, Abelson tyrosine kinase (c-Abl) was first studied in chronic myelogenous leukaemia, and its role in lymphocytes has been well characterised. c-Abl is involved in B-cell development and CD19-associated B-cell antigen receptor (BCR) signalling. Although c-Abl regulates different metabolic pathways, the role of c-Abl is still unknown in B-cell metabolism. In this study, B-cell-specific c-Abl knockout (KO) mice (Mb1Cre+/- c-Ablfl/fl ) were used to investigate how c-Abl regulates B-cell metabolism and BCR signalling. We found that the levels of activation positive BCR signalling proximal molecules, phosphorylated spleen tyrosine kinase (pSYK) and phosphorylated Bruton tyrosine kinase (pBTK), were decreased, while the level of key negative regulator, phosphorylated SH2-containing inositol phosphatase 1 (pSHIP1), was increased in Mb1Cre+/- c-Ablfl/fl mice. Furthermore, we found c-Abl deficiency weakened the B-cell spreading, formation of BCR signalosomes, and the polymerisation of actin during BCR activation, and also impaired the differentiation of germinal center (GC) B-cells both in quiescent condition and after immunisation. Moreover, B-cell mitochondrial respiration and the expression of B-cell metabolism-regulating molecules were downregulated in c-Abl deficiency mice. Overall, c-Abl, which involved in actin remodelling and B-cell metabolism, positively regulates BCR signalling and promotes GC differentiation.

Overexpression of PID1 reduces high density lipoprotein level and functionality in swine.

Phosphotyrosine interaction domain 1 (PID1), a protein with a phosphotyrosine-binding (PTB) domain, interacts with the lipoprotein receptor-related protein 1 (LRP1) to reduce the insulin sensitivity of adipocyte. Considering the role of LRP1 in lipid metabolism, we investigated the effect of PID1 on the content and biological activities of serum lipoproteins in pigs. PID1-transgenic pigs were genetated by sperm and magnetic nanoparticles-mediated method. The levels of PID1 in PID1-transgenic pig's liver were higher than that in the wild-type pig's liver. We found that serum levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) were significantly reduced in PID1-transgenic pigs. On the other hand, PID1-transgenic pigs displayed increased non-HDL-C levels. Serum levels of total cholesterol and triglycerides were comparable between the PID1-transgenic and the wild-type pigs. Further, the HDL isolated from PID1-transgenic pigs showed a significant reduction in cholesterol efflux ability. In addition, serum superoxide dismutase activity of PID1-transgenic pigs was also obviously lowered compared with that of wild type pigs. In conclusion, these results suggest that PID1 might be able to adjust HDL-C levels in serum and HDL cholesterol efflux ability.

[Research on Spectrum Radiation Characteristics of a New Type Infrared/ Ultraviolet Dual Color Decoy].

The advantage of traditional MTV infrared decoys which are mainly consist of magnesium, Teflon and VITON is that it emits high radiant energy, so it is an effective countermeasure to traditional seekers which seek the target by heat source. The spectral radiant intensity which generated from high temperature combustion of MTV infrared decoys in near infrared region and ultraviolet band is very high, and that in Mid-IR region is relative lower, however the radiant intensity of real jet fighter in ultraviolet band is low and the infrared radiant intensity ratio of Mid-IR to near IR band is greater than 1. Thus, the traditional MTV infrared decoys are hardly able to counter the seekers equipped with dual color combined guidance system. Based on the spectral matching principle, we designed and prepared a new infrared/ultraviolet dual color decoy which is mainly consist of oxidant (wt% 45-75), fuel (wt% 10-25), energetic binder (wt% 25-50) and additives. We conducted theoretical calculations on combustion products of the reagent combinations using CEA (Chemic equilibrium & Application) software and initially determined the content of each component of the decoy formulation on the basis of the calculations results, then investigated the infrared radiation characteristics of decoys employing SR5000 spectrum radiometer and remote sensing interferometer spectrometer Tensor37 and analyzed the possible reasons for test results difference of the two systems separately from the test principle and calculation method, the testing environment, stability of testing results and other aspects. We studied the ultraviolet radiation characteristics of decoys using S2000 fiber optical spectrometer and the test results were consistent with the fighter ultraviolet radiant intensity which gained from theoretical calculation. We researched on the temperature characteristics of decoys by Imager IR 8325 mid-infrared thermal imager and it turned out that the dual color decoy is similar to the real fighter target in temperature characteristics. The results indicates that the infrared radiant intensity ratio of Mid-IR to near IR band is from 1 to 3 (1< I(3-5 microm) : I(1-3 microm) <3). The infrared radiant intensity in 3-5 pLm band is tunable from 0.9 to 2.5 kW x sr(-1) while the ultraviolet radiant intensity in 0.3-0.5 microm is about (20 +/- 5)W x sr(-1). The flame temperature is between 850-1100 degrees C. It is proved that the dual color decoy as-designed has excellent characteristics.

[Case-control study of relationship between polymorphisms of interleukin-4 gene and susceptibility of silicosis].

OBJECTIVE: To explore the relationship between polymorphisms of interleukin-4 (IL-4) gene (-33, +45, VNTR, +429, +448) and the susceptibility of silicosis. METHODS: In a case-control study, the case group consisted of 101 patients with silicosis, and was matched with the control group (121 workers without silicosis), according to the age, sex, nationality, working place, exposure to dust. The polymorphisms of IL-4 (five locus) detected by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS: There was no difference of age, exposure and smoking between case group and control group (P > 0.05). The two groups had good comparability. Only the GA genotype in the IL-4 (+429) locus was found, the genotypes of AA and GG were not found. The CC genotype in the IL-4 (+448) locus was found, the genotypes of CG and GG were not found. The frequencies of AA, GG and AG of IL-4 (+45) locus in the case and control groups were 55.4%, 10.9%, 33.7% and 62.0%, 11.6%, 26.4%, respectively, there was no the significant difference between case and control groups (P > 0.05). The frequencies of B1B1, B2B2 and B1B2 of IL-4 (VNTR) locus in the case and control groups were 73.3%, 1.0%, 25.7% and 68.6%, 1.7%, 29.8%, respectively, there was no the significant difference between case and control groups (P > 0.05). The frequencies of TT, CC and CT in IL-4 -33 locus in the case group were 55.4%, 11.9% and 32.7%, which were significantly higher than those (69.4%, 4.1%, 26.4%) in control group (P < 0.05). CONCLUSIONS: There was no relationship between IL-4 (+45, VNTR) genotypes and prevalence of silicosis in this study. The polymorphisms of IL-4 (+448) site were not found which may be related to the race. The relationship between genetic polymorphism of IL-4 (-33) locus and silicosis development was found, Workers with IL-4 (-33) allele C are susceptible to the silica.