The objective of this study was to investigate the relationship between PI3K/mTOR/RhoA signaling regulated cytoskeletal rearrangements and phagocytic capacity of macrophages. RAW264.7 macrophages were divided into four groups; blank control, negative control, PI3K-RNAi, and mTOR-RNAi. The cytoskeletal changes in the macrophages were observed. Furthermore, the phagocytic capacity of macrophages against Escherichia coli is reported as mean fluorescence intensity (MFI) and percent phagocytosis. Transfection yielded 82.1 and 81.5% gene-silencing efficiencies against PI3K and mTOR, respectively. The PI3K-RNAi group had lower mRNA and protein expression levels of PI3K, mTOR, and RhoA than the blank and negative control groups (Р<0.01). The mTOR-RNAi group had lower mRNA and protein levels of mTOR and RhoA than the blank and the negative control groups (Р<0.01). Macrophages in the PI3K-RNAi group exhibited stiff and inflexible morphology with short, disorganized filopodia and reduced number of stress fibers. Macrophages in the mTOR-RNAi group displayed pronounced cellular deformations with long, dense filopodia and an increased number of stress fibers. The PI3K-RNAi group exhibited lower MFI and percent phagocytosis than blank and negative control groups, whereas the mTOR-RNAi group displayed higher MFI and percent phagocytosis than the blank and negative controls (Р<0.01). Before and after transfection, the mRNA and protein levels of PI3K were both positively correlated with mTOR and RhoA (Р<0.05), but the mRNA and protein levels of mTOR were negatively correlated with those of RhoA (Р<0.05). Changes in the phagocytic capacity of macrophages were associated with cytoskeletal rearrangements and were regulated by the PI3K/mTOR/RhoA signaling pathway.

Some research has shown that PM2.5 causes Th1/Th2 immune imbalance and aggravates asthma. However, the exact mechanism of PM2.5 causing aggravation of asthma remains unclear. The purpose of this study was to investigate whether exposure to PM2.5 exacerbates Th1/Th2 immune imbalance through the Notch signaling pathway. Eight-week-old SPF female BALF/c mice were sensitized by ovalbumin to establish an asthma mouse model. PM2.5 exposure was carried out by aerosol inhalation of PM2.5 (510 μg/m³) after each provocation. The lung function of mice was measured and Splenic T lymphocyte subsets were detected. Notch signaling pathway was tested. The levels of interferon (IFN)-γ and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid were determined. The results showed that the expression of the mRNA and protein of Notch1 and Hes1 in the asthma group were significantly higher than those in healthy controls. The levels of IL-4 were also remarkably high; while the levels of IFN-γ were remarkably low in serum and BALF, the Th1% and Th1/Th2 ratios were significantly lower, and Th2% was significantly higher in the asthma group than in the healthy controls. PM2.5 promoted further activation of the Notch signaling pathway and aggravated Th1/Th2 immune imbalance in asthmatic mice. γ-secretase inhibitor can partially inhibit the activation of the Notch signaling pathway and alleviate aggravation of immune imbalance. In conclusion, the asthmatic mice had a Th1/Th2 immune imbalance and an overactivated Notch signaling pathway. PM2.5 further aggravated Th1/Th2 immune imbalance by activating the Notch signaling pathway.

It’s unclear exactly how variations in a number of meteorological factors relate to the chance of being hospitalized with COPD. The majority of earlier research was incomplete and non-systematic, describing only the association between a single climatic element and hospitalization for COPD. The results were often inconsistent. The purpose of this study is to investigate the relationship between three meteorological factors (temperature, DTR, and relative humidity) and the daily hospital admissions of COPD in Qingyang, China, as well as to examine the lag effects of each meteorological indicator on various subgroups. Based on daily COPD hospital admissions and meteorological data in Qingyang City, China, from 2015 to 2019, a generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to examine the effects of three meteorological factors on COPD hospital admissions. At the same time, the 95th and 5th percentiles were utilized as the high and low effect nodes of each meteorological index to assess its relationship with COPD admission. Temperature, DTR, and relative humidity exhibited inverted J-, M-, and W-shaped exposure-response relationships with COPD admission. The negative effects of the cold effect and high DTR reached their peak at lag0-21. The RR values were 1.867 (95%CI:1.624,2.148) and 1.542 (95%CI:1.215,1.959), respectively. The highest negative effect of low humidity was in lag0-7, with RR values of 1.239 (95% CI:1.116,1.374). The three factors had a greater negative impact on those over 65 years old. Women were more susceptible to the cold, but men were more vulnerable to high DTR and low humidity. The study found significant correlations between meteorological factors and COPD hospitalizations. Lower temperatures, higher diurnal temperature variation, and lower humidity were associated with increased admission risks, with differential impacts observed across age groups and genders.