Attenuated T cell activation and rearrangement of T cell receptor ß repertoire in silica nanoparticle-induced pulmonary fibrosis of mice.

Silica nanoparticles (SiNPs) cause pulmonary fibrosis through a complex immune response, but the underlying mechanisms by which SiNPs interact with T cells and affect their functions remain unclear. The T cell receptor (TCR) repertoire is closely related to T cell activation and proliferation and mediates innate and adaptive immunity. High-throughput sequencing of the TCR enables comprehensive monitoring of the immune microenvironment. Here, the role of the TCRß repertoire was explored using a mouse model of SiNP-induced pulmonary fibrosis and a co-culture of RAW264.7 and CD4+ T cells. Our results demonstrated increased TCRß expression and decreased CD25 and CD69 expression in CD4+ T cells from peripheral blood and lung collected 14 days after the induction of pulmonary fibrosis by SiNPs. Simultaneously, SiNPs significantly decreased CD25 and CD69 expression in CD4+ T cells in vitro via RAW264.7 cell presentation. Mechanistically, pLCK and pZap70 expression, involved in mediating T cell activation, were also decreased in the lung of mice with SiNP-induced pulmonary fibrosis. Furthermore, the profile of the TCRß repertoire in mice with SiNP-induced pulmonary fibrosis showed that SiNPs markedly altered the usage of V genes, VJ gene combinations, and CDR3 amino acids in lung tissue. Collectively, our data suggested that SiNPs could interfere with T cell activation by macrophage presentation via the LCK/Zap70 pathway and rearrange the TCRß repertoire for adaptive immunity and the pulmonary microenvironment.

Effects of ambient PM2.5 on development of psoriasiform inflammation through KRT17-dependent activation of AKT/mTOR/HIF-1α pathway.

Exposure to fine particulate matter (PM2.5) has significant effects on human skin health, mainly disrupting skin homeostasis and accelerating aging. To date, the effects of PM2.5 on psoriasis (PSO) have not been elucidated. An ambient particulate matter exposed and well characterized imiquimod (IMQ)-induced psoriasis mouse model was established. Thirty male C57BL/6 mice aged 8 weeks were randomly divided into three groups: filtered air (FA) group (Control group), PSO+ FA group and PSO + PM2.5 group. A KRT17 knockdown (KRT17-KD) mouse model was simultaneously established by subcutaneously injecting KRT17-KD lentivirus. Forty male C57BL/6 mice were randomly divided into four groups: PSO + FA + KRT17-RNAi negative control lentivirus (KRT17-NC) group, PSO+ FA+ KRT17-KD group, PSO + PM2.5 + KRT17-NC group and PSO + PM2.5 + KRT17-KD group. PM2.5 exposure continued for 8 weeks. Psoriasis was induced by topically applying IMQ on the dorsal skin of the mice for 6 days during week 8. Morphometric and histological analyses were performed to investigate the changes in psoriatic lesions. Differentially expressed genes and enriched pathways were explored using bioinformatics analysis and showed that KRT17 gene and the vascular endothelial growth factor receptor signaling pathway were associated with psoriasis. HaCaT cells were stimulated with interleukin-17A and infected with KRT17-KD lentivirus to establish an in vitro KRT17 knockdown psoriasis cell model. Notably, PM2.5 exposure increased the expression of KRT17 protein and activated AKT/mTOR/HIF-1α signaling pathway in vivo. Moreover, specific agonist of AKT (740Y-P) reversed the decreased neovascularization induced by KRT17 knockdown through AKT/mTOR/HIF-1α signaling pathway in vitro. Consequently, PM2.5 exposure could promote the development and progression of psoriasis through KRT17-dependent activation of AKT/mTOR/HIF-1α signaling pathway.

The structure and component characteristics of partial nitrification biofilms under autotrophic and heterotrophic conditions.

The differences in the structure and component characteristics of partial nitrification biofilms between autotrophic and heterotrophic conditions were investigated in this work. Three-dimensional excitation-emission matrix fluorescence spectroscopy (EEM), fluorescence staining, and confocal laser scanning microscopy (CLSM) were used to determine differences in the architecture and extracellular polymeric substance (EPS) distribution of the autotrophic and heterotrophic biofilms. Partial nitrification was successfully achieved, and the results demonstrated that an appropriate amount of organic carbon (chemical oxygen demand (COD)/N = 2.6) is advantageous for obtaining better partial nitrification. The final ammoniation and nitrosation rates achieved were 97 and 99 %, respectively. Proteins (PN) and polysaccharides (PS) were dominant in the tightly bound EPS (TB-EPS) of autotrophic and heterotrophic biofilms, with PN/PS ratios of 0.96 and 0.69, respectively. Proteins, lipids, α-D-glucopyranose polysaccharides, and nucleic acids were mostly present within the layers of biofilms, but they were distributed in the upper-middle portion of the autotrophic biofilm and increased with depth from the upper layer in the heterotrophic biofilms.

Computed tomography radiomics study of invasion and instability of lung adenocarcinoma manifesting as ground glass nodule.

Background: Ground-glass nodule (GGN) is the most common manifestation of lung adenocarcinoma on computed tomography (CT). Clinically, the success rate of preoperative diagnosis of GGN by puncture biopsy and other means is still low. The aim of this study is to investigate the clinical and radiomics characteristics of lung adenocarcinoma presenting as GGN on CT images using radiomics analysis methods, establish a radiomics model, and predict the classification of pathological tissue and instability of GGN type lung adenocarcinoma. Methods: This study retrospectively collected 249 patients with 298 GGN lesions who were pathologically confirmed of having lung adenocarcinoma. The images were imported into the Siemens scientific research prototype software to outline the region of interest and extract the radiomics features. Logistic model A (a radiomics model to identify the infiltration of lung adenocarcinoma manifesting as GGNs) was established using features after the dimensionality reduction process. The receiver operating characteristic (ROC) curve of the model on training set and the verification set was drawn, and the area under the curve (AUC) was calculated. Second, a total of 112 lesions were selected from 298 lesions originating from CT images of at least two occasions, and the time between the first CT and the preoperative CT was defined as not less than 90 days. The mass doubling time (MDT) of all lesions was calculated. According to the different MDT diagnostic thresholds instability was predicted. Finally, their AUCs were calculated and compared. Results: There were statistically significant differences in age and lesion location distribution between the "noninvasive" lesion group and the invasive lesion group (P<0.05), but there were no statistically significant differences in sex (P>0.05). Model A had an AUC of 0.89, sensitivity of 0.75, and specificity of 0.86 in the training set and an AUC of 0.87, sensitivity of 0.63, and specificity of 0.90 in the validation set. There was no significant difference statistically in MDT between "noninvasive" lesions and invasive lesions (P>0.05). The AUCs of radiomics models B1, B2 and B3 were 0.89, 0.80, and 0.81, respectively; the sensitivities were 0.71, 0.54, and 0.76, respectively; the specificities were 0.83, 0.77, and 0.60, respectively; and the accuracies were 0.78, 0.65, and 0.69, respectively. Conclusions: There were statistically significant differences in age and location of lesions between the "noninvasive" lesion group and the invasive lesion group. The radiomics model can predict the invasiveness of lung adenocarcinoma manifesting as GGNs. There was no significant difference in MDT between "noninvasive" lesions and invasive lesions. The radiomics model can predict the instability of lung adenocarcinoma manifesting as GGN. When the threshold of MDT was set at 813 days, the model had higher specificity, accuracy, and diagnostic efficiency.

The Association of Coronary Fat Attenuation Index Quantified by Automated Software on Coronary Computed Tomography Angiography with Adverse Events in Patients with Less than Moderate Coronary Artery Stenosis.

OBJECTIVE: This study analyzed the relationship between the coronary FAI on CCTA and coronary adverse events in patients with moderate coronary artery disease based on machine learning. METHODS: A total of 172 patients with coronary artery disease with moderate or lower coronary artery stenosis were included. According to whether the patients had coronary adverse events, the patients were divided into an adverse group and a non-adverse group. The coronary FAI of patients was quantified via machine learning, and significant differences between the two groups were analyzed via t-test. RESULTS: The age difference between the two groups was statistically significant (p < 0.001). The group that had adverse reactions was older, and there was no statistically significant difference between the two groups in terms of sex and smoking status. There was no statistical significance in the blood biochemical indexes between the two groups (p > 0.05). There was a significant difference in the FAIs between the two groups (p < 0.05), with the FAI of the defective group being greater than that of the nonperforming group. Taking the age of patients as a covariate, an analysis of covariance showed that after excluding the influence of age, the FAIs between the two groups were still significantly different (p < 0.001).

Relationships between the coronary fat attenuation index for patients with heart-related disease measured automatically on coronary computed tomography angiography and coronary adverse events and degree of coronary stenosis.

Background: Pericoronary artery coronary tissue (PACT) is a type of epicardial fat that can reflect the state of the coronary artery (inflammation, etc.). However, it cannot be reasonably and efficiently utilized in routine computed tomography (CT) examination. The aim of this study was to use artificial intelligence (AI) software to analyze coronary computed tomography angiography (CCTA) and measure the coronary perivascular fat attenuation index (FAI) of patients. The relationship between FAI and the occurrence of coronary adverse events and the degree of coronary stenosis were further analyzed. Methods: This study involved patients who experienced CCTA in West China Hospital, Sichuan University, from January 2012 to December 2012. These patients were followed up to 2020 and classified according to the occurrence of coronary adverse events and the degree of stenosis of the lumen. For all patients, AI software was used to analyze the CCTA images of patients, and the FAI of 3 coronary arteries, the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA), was measured. Moreover, the relationship between FAI and patients with different degrees of coronary stenosis and adverse coronary events was determined. Results: Comparisons between any 2 groups showed that the differences in the FAI among the 4 groups for the LAD were significant (all P values <0.05). There were no significant differences between the group with less-than-moderate stenosis (Mb) without adverse events and the group with moderate-or-above stenosis (M) with no adverse events for the LCX (P>0.05). For the remaining groups, FAI values exhibited statistically significant differences (P<0.05). According to the degree of lumen stenosis, the patients were divided into groups according to LAD, LCX, and RCA and the sum of the 3 vessels. There were significant differences in coronary FAI among the groups with different degrees of lumen stenosis for the sum of the 3 vessels, the LAD, and the LCX (P<0.05). Conclusions: FAI can reflect the state of the coronary artery, which is related to inflammation of the coronary lumen. Moreover, there is a relationship between FAI and the degree of stenosis in the coronary lumen: the narrower the coronary lumen is, the higher the FAI around the lumen.

Moderate physical activity against effects of short-term PM2.5 exposure on BP via myokines-induced inflammation.

Exposure to PM2.5 increases blood pressure (BP) and cardiovascular morbidity and mortality. We conducted a randomized controlled panel study in Shijiazhuang, China among 55 healthy college students randomly assigned to either the control (CON) or SPORTS group with intervention of 2000 m jogging in 20 min for 3 times in 4 days, and 3-round health examinations from November 15, 2020 to December 6, 2020. We aimed to evaluate whether moderate physical activity (PA) protected BP health against PM2.5 exposure and explore potential mechanisms through myokines and inflammation. Individual PM2.5 exposure was calculated based on outdoor and indoor PM2.5 concentration monitoring data as well as time-activity diary of each subject. In the CON group, the exposure-response curve for SBP was linear with a threshold concentration of approximately 31 µg/m3, while an increment of SBP level was 4.38 mm Hg (95%CI: 0.17 mm Hg, 8.59 mm Hg) at lag03 for each 10-µg/m3 increase in PM2.5, using linear mixed-effect models. For inflammatory indicators, PM2.5 exposure was associated with significant increases in eosinophil counts and proportion in CON group, but decreases in MCP-1 and TNF-α in SPORTS group. Meanwhile, higher myokines including CLU and IL-6 were observed in SPORTS group compared to the CON group. Further mediation analyses revealed that eosinophil counts mediated the elevated BP in CON group, whereas MCP-1 and TNF-α were also crucial mediating cytokines for the SPORTS group, as well as CLU and IL-6 acted as mediators on BP and inflammation indicators in SPORTS group. This study suggests that moderate PA could counteract the elevated BP induced by PM2.5 exposure via myokines-suppressed inflammation pathways.

Evidence from two cases of asymptomatic infection with SARS-CoV-2: Are 14 days of isolation sufficient?

Among 78 laboratory-confirmed cases, we found two asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his RT-PCR test was still positive on the 15th day. We found that there may be virus carriers in the asymptomatic population with an epidemiological contact history. After 14 days of isolation, those with asymptomatic infection may still carry the virus, which means a risk of transmission, presenting a new challenge for the management of home isolation.