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Bacillus Calmette-Guérin (BCG) vaccination induces a type of immune memory known as "trained immunity", characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27's higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces. [ABSTRACT FROM AUTHOR]

The "Fengqiao Experience" has risen from the "local experience" in the early days to the "national experience" now. Although it has gone through twists and turns, it is full of exuberant and strong vitality. Fengqiao Experience is the experience of grass-roots mass governance based on people's livelihood and other factors, so this paper studies the challenges faced by the application of "Fengqiao Experience" and the internal relationship between the experience and people's livelihood from the perspective of people's livelihood and summarizes the realization path of cairying forward the "Fengqiao Experience" from the perspective of people's livelihood. Strengthening the construction of grassroots Party organizations, taking the mass line and implementing autonomy, rule by virtue and rule by law are the ways to carry forward the "Fengqiao Experience" in the new era, which has certain guiding significance for reality. [ABSTRACT FROM AUTHOR]

Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence. [ABSTRACT FROM AUTHOR]

Hydrogels are an excellent type of material that can be utilized as a platform for cell culture. However, when a bulky hydrogel forms on the inside of cancer cells, the result would be different. In this study, we demonstrate a method for in situ gelation inside cancer cells that can efficiently induce cell death. Glutathione-responsive proteinosomes with good biocompatibility were prepared as carriers for sodium alginate to be endocytosed by cancer cells, where the chelation between sodium alginate and free calcium ions in the culture medium occurs during the diffusion process. The uptake of the hydrogel-loaded proteinosomes into the cancer cells, and then the triggered release of hydrogel with concomitant aggregation, was well-confirmed by monitoring the change of the Young's modulus of the cells based on AFM force measurements. Accordingly, when a large amount of hydrogel formed in cells, the cell viability would be inhibited by ~90% by MTT assay at a concentration of 5.0 μM of hydrogel-loaded proteinosomes after 48 h incubation, which clearly proves the feasibility of the demonstrated method for killing cancer cells. Although more details regarding the mechanism of cell death should be conducted in the near future, such a demonstrated method of in situ gelation inside cells provides another choice for killing cancer cells. [ABSTRACT FROM AUTHOR]

Stability of near-infrared (NIR) emission form Bi doped 42.5SiO2-12.5B2O3-25Al2O3-20RO (SBAR, R=Ca, Sr, Ba) glasses under treatment between annealing and softening temperature were studied. Results show that the thermal stability of Bi-NIR-emitting centers in SBAR glasses generally decreases with the increase of the radius of modifier cations but is greatly higher that in similar alkali glasses. Comparative experiments indicate these phenomena can be understood by the tendency that the smaller and higher charged alkaline earth ions as higher field strength modifier cations will increase the concentration of negative charge on non-bridging oxygens and also help to stabilize the non-bridging oxygens, which can restrain the thermally activated diffusion and valence change of Bi-activated centers, respectively. The results can provide an improved understanding for the NIR-emitting thermal stability of Bi doped glasses and a scientific reference for composition design of Bi-doped optical fiber. [ABSTRACT FROM AUTHOR]

Moderate-resolution imaging spectroradiometer (MODIS) gross primary production (GPP) was compared with estimated GPP (GPP_EC) from eddy covariance measurements over an alpine meadow on the Tibetan Plateau in 2005-2007. The MODIS GPP (GPP_MOD17A2) with a bias of -0.38 g C m-2 d-1 (i.e., about -40.58% of the mean of the GPP_EC) strongly underestimated the GPP_EC for the alpine meadow. The MODIS GPP was recalibrated using measured surface meteorological data, including photosynthetically active radiation (PAR), daily minimum air temperature (Tamin) and daytime mean vapor pressure deficit (VPD), revised fractional photosynthetically active radiation (FPAR), and the revised maximum light use efficiency (LUEmax) of 0.81 g C MJ-1 (compared with the default value of 0.68 g C MJ-1 for grassland in the MODIS GPP algorithm) for the alpine meadow. The MODIS-based FPAR was about 14.70% larger than the surface-estimated FPAR using surface-measured leaf area index (LAI) data. Additionally, the temporal resolution of surface-measured LAI data was relatively low. Therefore, the linear relationship between surface-measured LAI and MODIS-based LAI was established (R² > 0.80, P < 0.001). Then the revised MOD17A2 datasets were used to calculate the revised FPAR. The revised LUEmax was optimized from the MOD17A2 algorithm using daily surface measurements, including LAI, PAR, VPD, Tamin and GPP_EC. The calibrated MOD17A2 algorithm could explain 88% of GPP_EC variance for the alpine meadow. The bias between GPP_MOD17A2 and calculated GPP from the MOD17A2 algorithm using surface-measured PAR, Tamin, and VPD, MODIS-based FPAR, and the default LUEmax of 0.68 g C MJ-1 was -0.17 g C m-2 d-1 (i.e., about -17.60% of the mean of the GPP_EC). The underestimation of LUEmax caused a 13.78% underestimation of GPP. In contrast, the overestimation of FPAR resulted in a 7.17% overestimation of GPP. The net effect of meteorology data and FPAR resulted in a 13.84% underestimation of GPP. These results showed that MODIS-based meteorology data, FPAR, and LUEmax for the alpine meadow needed to be adjusted. [ABSTRACT FROM AUTHOR]