The mediation effect of asprosin on the association between ambient air pollution and diabetes mellitus in the elderly population in Taiyuan, China.

Evidence around the relationship between air pollution and the development of diabetes mellitus (DM) remains limited and inconsistent. To investigate the potential mediation effect of asprosin on the association between fine particulate matter (PM2.5), tropospheric ozone (O3) and blood glucose homeostasis. A case-control study was conducted on a total of 320 individuals aged over 60 years, including both diabetic and non-diabetic individuals, from six communities in Taiyuan, China, from July to September 2021. Generalized linear models (GLMs) suggested that short-term exposure to PM2.5 was associated with elevated fasting blood glucose (FBG), insulin resistance index (HOMA-IR), as well as reduced pancreatic ß-cell function index (HOMA-ß), and short-term exposure to O3 was associated with increased FBG and decreased HOMA-ß in the total population and elderly diabetic patients. Mediation analysis showed that asprosin played a mediating role in the relationship of PM2.5 and O3 with FBG, with mediating ratios of 10.2% and 18.4%, respectively. Our study provides emerging evidence supporting that asprosin mediates the short-term effects of exposure to PM2.5 and O3 on elevated FBG levels in an elderly population. Additionally, the elderly who are diabetic, over 70 years, and BMI over 24 kg/m2 are more vulnerable to air pollutants and need additional protection to reduce their exposure to air pollution.

Hepatocyte miR-21-5p-deficiency alleviates APAP-induced liver injury by inducing PPARγ and autophagy.

Acetaminophen (APAP)-induced liver injury is one of the most frequent causes of acute liver failure worldwide. Significant increases in the levels of miRNA-21 in both liver tissues and plasma have been observed in APAP-overdosed animals and humans. However, the mechanistic effect of miRNA-21 on acute liver injury remains unknown. In this study, we generated a new hepatocyte-specific miRNA-21 knockout (miR-21-HKO) mouse line. miR-21-HKO and the background-matched sibling wild-type (WT) mice were treated with a toxic dose of APAP. Compared with WT mice, miR-21 HKO mice showed an increased survival, a reduction of necrotic hepatocytes, and an increased expression of light chain 3 beta, which suggested an autophagy activation. The expression of PPARγ was highly induced in the livers of miR-21-HKO mice after a 2-h APAP treatment, which preceded the activation of LC3B at the 12 h APAP treatment. miR-21 negatively regulated PPARγ protein expression by targeting its 3'-UTR. When PPARγ function was blocked by a potent antagonist GW9662 in miR-21-HKO mice, the autophage activation was significantly diminished, suggesting an indispensable role of PPARγ signaling pathway in miR-21-mediated hepatotoxicity. Taken together, hepatocyte-specific depletion of miRNA-21 alleviated APAP-induced hepatotoxicity by activating PPARγ and autophagy, demonstrating a crucial new regulatory role of miR-21 in APAP-mediated liver injury.

HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus.

Mitogen-activated protein kinase (MAPK) cascades play important roles in disease resistance in model plant species. However, the functions of MAPK signaling pathways in crop disease resistance are largely unknown. Here we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune system. HvMPK4 is identified to play a negative role in barley immune response against Bgh, as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh infection. Furthermore, the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4, and the activated HvMKK1DD variant specifically phosphorylates HvMPK4 in vitro. Moreover, the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1DD. Phosphorylation assay coupled with mutagenesis analyses identifies S122, T284, and S347 in HvWRKY1 as the major residues phosphorylated by HvMPK4. HvWRKY1 is phosphorylated in barley at the early stages of Bgh infection, which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression activity. Our data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

The expression of squalene epoxidase in human gastric cancer and its clinical significance.

Context: Squalene epoxidase (SQLE) is overexpressed in a variety of tumors, which may play an important role in their tumorigenesis, development, and prognosis. Aims: The aim of this study is to investigate the expression of SQLE and explore its clinicopathological significance in gastric cancer. Settings and Design: The correlation between its positive expression and the pathological characteristics of patients (such as sex, age, tumor size, survival, tumor differentiation, TNM staging, and lymph node metastasis) was analyzed. Materials and Methods: Immunohistochemical method was used to detect its expression in 107 cases of gastric carcinoma and 34 cases of tumor-adjacent tissues. Statistical Analysis Used: Counting data were analyzed by Chi-square test. Its overall survival was analyzed by Kaplan-Meier method and log-rank test. Its hazard factors were analyzed by Cox multivariate analysis. Results: The positive rate of SQLE in gastric cancer is 67.3%, which is higher than that in tumor-adjacent tissues (17.6%), <0.001. Expression of SQLE is closely related to tumor differentiation, TNM staging and lymph node metastasis (P = 0.030, P = 0.009, and P = 0.011, respectively). Furthermore, compared with those low expression of SQLE, the patients of overexpression had worse overall survival by Kaplan-Meier analysis (P = 0.025). Cox multivariate analysis shows that lymph node metastasis, tumor differentiation, SQLE, and TNM staging are independent factors for prognosis of gastric cancer (P = 0.003, 0.020, 0.018, and P = 0.001 respectively). Conclusions: SQLE is overexpressed in gastric cancer. It could be used for the diagnosis and prognosis of the gastric cancer patients.

Omalizumab for Chinese patients with moderate-to-severe allergic asthma in real-world clinical setting: a prospective, observational study.

BACKGROUND: We aimed to investigate the effectiveness of omalizumab, a monoclonal anti-immunoglobulin E antibody, in Chinese patients with moderate-to-severe allergic asthma in real-world clinical practice. METHODS: This single-centre, prospective, observational study included Chinese patients aged 14-75 years with moderate-to-severe allergic asthma according to the Global Initiative for Asthma criteria. Omalizumab was administered subcutaneously, and the investigator collected real-world data on exacerbations, steroid exposure, pulmonary function and laboratory assessments at weeks 16, 24, 52, 104 and 156 after treatment initiation. The primary outcome was reduced exacerbations, measured as the proportion of patients with exacerbations in the year following omalizumab initiation. Bowker's test for paired proportions was performed to compare exacerbation rates before and after treatment initiation. A generalised linear mixed model was used to compare the number of exacerbations. RESULTS: The mean treatment duration was 46.6 weeks for the full analysis set (n=398). The proportion of patients with exacerbations in the year before and after omalizumab initiation was 80.4% (181/225) and 18.7% (42/225) (difference: -61.8%, 95% CI -68.5 to -54.0, p<0.0001), respectively. At week 52, 67.4% of patients discontinued oral corticosteroids, and 19.5% reduced inhaled corticosteroids. The Asthma Control Test scores increased by 4.6 at week 52 from baseline (p<0.001). Forced expiratory volume in 1 s increased by 11.2% and 9.0% at weeks 24 and 52, respectively, from baseline (p<0.01). Injection site reactions (5.2%) were the most frequently reported adverse event. CONCLUSIONS: In real-world clinical practice, omalizumab treatment remarkably reduced exacerbations in Chinese patients with moderate-to-severe asthma. Omalizumab reduced the use of oral corticosteroids and improved asthma control and pulmonary function.

Epidemiological characteristics of paediatric Omicron infection during the outbreak of SARS-CoV-2 infection during March-May in 2022 in Shanghai, China.

This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents <18 years. The incidence rate of SARS-CoV-2 infections in children was 153 per 10,000. Of all paediatric cases, 50% reported to be clinically symptomatic within 1-3 days after PCR confirmation by parents or themselves, with 36.3% and 18.9% of paediatric cases reporting fever and cough. Also, 58.4% of paediatric cases had received at least one dose of the COVID-19 vaccine and 52.1% had received two doses of the COVID-19 vaccination. Our findings are informative for the implementation of appropriate measures to protect children from the threat of SARS-CoV-2 infection.

Xanthine-derived reactive oxygen species exacerbates adipose tissue disorders in male db/db mice induced by real-ambient PM2.5 exposure.

Epidemiological and experimental data have associated exposure to fine particulate matter (PM2.5) with various metabolic dysfunctions and diseases, including overweight and type 2 diabetes. Adipose tissue is an energy pool for storing lipids, a necessary regulator of glucose homeostasis, and an active endocrine organ, playing an essential role in developing various related diseases such as diabetes and obesity. However, the molecular mechanisms underlying PM2.5-impaired functions in adipose tissue have rarely been explored. In this work, metabolomics based on liquid chromatography-mass spectrometry was performed to study the adverse impacts of PM2.5 exposure on brown adipose tissue (BAT) and white adipose tissue (WAT) in the diabetic mouse model. We found the effects of PM2.5 exposure by comparing the different metabolites in both adipose tissues of male db/db mice using real-ambient PM2.5 exposure. The results showed that PM2.5 exposure changed the purine metabolism in mice, especially the dramatic increase of xanthine content in both WAT and BAT. These changes led to significant oxidative stress. Then the results from real-time quantitative polymerase chain reaction showed that PM2.5 exposure could cause the production of inflammatory factors in both adipose tissues. Moreover, the increased reactive oxygen species (ROS) promoted triglyceride accumulation in WAT and inhibited its decomposition, causing increased WAT content in db/db mice. In addition, PM2.5 exposure significantly suppressed thermogenesis and affected energy metabolism in the BAT of male db/db mice, which may deteriorate insulin sensitivity and blood glucose regulation. This research demonstrated the impact of PM2.5 on the adipose tissue of male db/db mice, which may be necessary for public health.

T-cell exhaustion: A potential target biomarker of the tumour microenvironment affecting oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (EAC) is one of the most common malignant tumours, and the number of patients is increasing year by year. T-cell exhaustion (TEX) is an important risk factor for tumour immunosuppression and invasion, but its underlying mechanism in the pathogenesis of EAC is not clear. METHODS: Unsupervised clustering was performed to screen relevant genes based on Gene Set Variation Analysis scores of the three pathways of the HALLMARK gene set IL2/IFNG/TNFA. Multiple enrichment analyses and data combinations were used to depict the relationship between TEX-related risk models and CIBERSORTx immune infiltrating cells. In addition, to explore the impact of TEX on EAC therapeutic resistance, we assessed the impact of TEX risk models on the therapeutic sensitivity of various novel drugs using single-cell sequencing and searched for their potential therapeutic targets and cellular communication. RESULTS: Four risk clusters of EAC patients were identified by unsupervised clustering and searched for potential TEX-related genes. Based on this, LASSO regression and decision trees were used to construct risk prognostic models containing a total of three TEX-associated genes in EAC. The results showed that TEX risk scores were significantly associated with the survival prognosis of EAC patients in both the Cancer Genome Atlas dataset and the independent validation set of Gene Expression Omnibus. Immune infiltration and cell communication analyses identified mast cell resting as a protective factor in TEX, and pathway enrichment analyses showed that the TEX risk model was highly associated with multiple chemokines as well as inflammation-associated pathways. In addition, higher TEX risk scores were associated with a weak responsiveness to immunotherapy. CONCLUSION: We describe the immune infiltration, prognostic significance and potential possible mechanisms of TEX in the EAC patient population. This is a novel attempt to promote the development of novel therapeutic modalities and immunological target construction for oesophageal adenocarcinoma. It is expected to make a potential contribution to advancing the exploration of immunological mechanisms and the opening of target drugs in EAC.

Analysis of clinical diagnosis and treatment of intestinal volvulus.

BACKGROUND: The aim of this study is to investigate the clinical characteristics and treatment experience of intestinal volvulus, and to analyze the incidence of adverse events and related risk factors of intestinal volvulus. METHODS: Thirty patients with intestinal volvulus admitted to the Digestive Emergency Department of Xijing Hospital from January 2015 to December 2020 were selected. The clinical manifestations, laboratory tests, treatment and prognosis were retrospectively analyzed. RESULTS: A total of 30 patients with volvulus were enrolled in this study, including 23 males (76.7%), with a median age of 52 years (33-66 years). The main clinical manifestations were abdominal pain in 30 cases (100%), nausea and vomiting in 20 cases (67.7%), cessation of exhaust and defecation in 24 cases (80%), and fever in 11 cases (36.7%). The positions of intestinal volvulus were jejunum in 11 cases (36.7%), ileum and ileocecal in 10 cases (33.3%), sigmoid colon in 9 cases (30%). All 30 patients received surgical treatment. Among the 30 patients underwent surgery, 11 patients developed intestinal necrosis. We found that the longer the disease duration (> 24 h), the higher the incidence of intestinal necrosis, and the higher the incidence of ascites, white blood cell count and neutrophil ratio in the intestinal necrosis group were significantly higher than those in the non-intestinal necrosis group (p < 0.05). After treatment, 1 patient died of septic shock after operation, and 2 patients with recurrent volvulus were followed up within 1 year. The overall cure rate was 90%, the mortality rate was 3.3%, and the recurrence rate was 6.6%. CONCLUSION: Laboratory examination, abdominal CT and dual-source CT are very important for the diagnosis of volvulus in patients with abdominal pain as the main symptom. Increased white blood cell count, neutrophil ratio, ascites and long course of disease are important for predicting intestinal volvulus accompanied by intestinal necrosis. Early diagnosis and timely intervention can save lives and prevent serious complications.

Upper respiratory tract microbiota is associated with small airway function and asthma severity.

BACKGROUND: Characteristics of airway microbiota might influence asthma status or asthma phenotype. Identifying the airway microbiome can help to investigate its role in the development of asthma phenotypes or small airway function. METHODS: Bacterial microbiota profiles were analyzed in induced sputum from 31 asthma patients and 12 healthy individuals from Beijing, China. Associations between small airway function and airway microbiomes were examined. RESULTS: Composition of sputum microbiota significantly changed with small airway function in asthma patients. Two microbiome-driven clusters were identified and characterized by small airway function and taxa that had linear relationship with small airway functions were identified. CONCLUSIONS: Our findings confirm that airway microbiota was associated with small airway function in asthma patients.

Prognostic value of RILPL2 and its correlation with tumor immune microenvironment and glycolysis in non-small cell lung cancer.

Rab-interacting lysosomal protein - like 2 (RILPL2) has been reported to be associated with prognosis and tumor biological functions in breast cancer and endometrial carcinoma. However, its expression and functional role in non-small cell lung cancer (NSCLC) remain unclear. The expression and clinical data of lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) were downloaded from the TCGA database. The expression of RILPL2 in NSCLC cell lines was verified by the Western blot. We used online databases and bioinformatics analysis tools to explore its prognostic value, potential biological functions, and correlations with tumor immune microenvironment.The expression of RILPL2 was significantly lower in NSCLC compared with adjacent normal tissues. Low RILPL2 expression was associated with worse overall survival (OS) in NSCLC. The GO analysis showed RILPL2 was comprehensively involved in immune activity. RILPL2 expression was significantly positively correlated with the infiltration levels of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells (P < 0.001), and it was also significantly positively correlated with programmed cell death ligand 1 (PD-L1/CD274) (P < 0.001). High RILPL2 expression could predict better immunotherapy response and prognosis in the immunotherapy cohort. The GSEA analysis showed low RILPL2 expression was associated with glycolysis process in LUAD, which was verified in vitro.These results showed RILPL2 expression was correlated with prognosis, tumor microenvironment, and immunotherapy response in NSCLC. Besides, RILPL2 may regulate glycolysis in LUAD.

[Effects of Oyster Shell Powder and Lime on Availability and Forms of Phosphorus and Enzyme Activity in Acidic Paddy Soil].

Soil acidification improvement in the main grain production regions of southern China is an important issue to enhance the quality of cultivated land and promote grain yield. In order to explore the effects of oyster shell powder and lime on acidity and availability and inorganic forms of phosphorus in acidic paddy soil, a pot experiment was performed using oyster shell powder and lime amendments with dosages of 0.05%, 0.10%, and 0.15%. The results showed that both oyster shell powder and lime significantly (P<0.05) increased the pH and decreased exchangeable acid content of paddy soil. The improvement effects increased with the dosage of soil amendments. Under the same amendment dosage, the effects of lime on soil pH and acidity were higher than those of oyster shell powder. Both lime and oyster shell powder significantly increased the content of available P extracted using H2SO4-P, Bray-1 P, and Olsen-P techniques. The contents of inorganic P in soils decreased in the order of Fe-P>Al-P>Ca-P. The application of lime and oyster shell powder significantly increased the contents of Al-P and Fe-P in soil. Compared with the control treatment, lime and oyster shell power increased Al-P and Fe-P by 26.3%-37.4% and 7.9%-23.7%, respectively. However, there was no significant difference in Al-P content among treatments of the three amendment dosages. The contents of Fe-P and Ca-P in soils increased with an increased dosage of amendments. The activities of DHA, ALP, and IPP and the copy number of the phoD gene in soil increased with the application of lime and oyster shell powder, whereas the activities of ACP and the copy numbers of phoC and pqqC decreased. The application of lime and oyster shell powder at a rate of 0.10% and 0.15% significantly (P<0.05) increased the yield of rice. The lime and oyster shell powder treatments at the dosage of 0.15% increased rice yield by 34.2% and 46.8%, respectively, whereas the amendment had no significant effect on straw biomass of the rice crop. Correlation analysis showed that soil pH and the ALP activity were significantly positively correlated with inorganic P and available P contents, respectively. These results suggested that lime and oyster shell power could effectively increase the content of available phosphorus by eliminating soil acidity and improving the phosphatase activity, which played a positive role in increasing crop yield.

The Relationship Between Serum Folate Level and Residual Renal Function in CAPD Patients.

Objective: To investigate the relationship between serum folate (FA) levels and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Clinical data were collected from 180 hospitalized patients who received CAPD regularly. Patients were divided into the FA deficiency group and the FA non-deficiency group according to serum FA level. Data on age, sex, PD vintage, hemoglobin, mean corpuscular volume, serum FA, total Kt/V, residual kidney Kt/V, peritoneum Kt/V, creatinine clearance (Ccr), ultrafiltration volume, cystatin C (cytC), serum creatinine (Scr), urea nitrogen, retinol-binding protein and the primary disease were gathered from 2 groups. Statistical methods were used to analyze the relationship between serum FA level and RRF. Results: Peritoneal Kt/V, cytC, Scr were higher, and residual kidney Kt/V was lower in FA deficiency group than in non-deficiency group. Univariate correlation showed the peritoneal Kt/V, cytC, Scr negatively correlated with serum FA while residual kidney Kt/V positively correlated with serum FA, and there was a simple linear regression relationship between serum FA and residual kidney Kt/V. Differences were statistically significant (P<0.05). Conclusion: There is a relationship between serum FA and RRF in CAPD patients. Prospective studies or trials should be performed to clarify the importance of FA supplementation on RRF during peritoneal dialysis.

Influences of ALDH2 on Cardiomyocyte Apoptosis in Heart Failure Rats Through Regulating PINK1-Parkin Signaling Pathway-Mediated Mitophagy.

The study aimed to investigate the influences of aldehyde dehydrogenase 2 (ALDH2) on cardiomyocyte apoptosis in heart failure (HF) rats through regulating the PTEN induced putative kinase 1 (PINK1)-Parkin signaling pathway-mediated mitophagy. The rat model of HF was established, and the rats were randomly divided into model group (HF model, n=20) and ALDH2 group (intervention with ALDH2, n=20), with a normal group (n=20) set. After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function index creatine kinase (CK) was measured, the status of myocardial tissue injury was determined using hematoxylin and eosin staining, and the apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The activity of ALDH2 was detected, and the expression levels of genes and proteins were measured through quantitative polymerase chain reaction (qPCR) and Western blotting assay. The model group had notably decreased fractional shortening (FS) and ejection fraction (EF) and remarkably increased left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) compared with the normal group (p<0.05). The activity of ALDH2 declined obviously in the model group. The myocardial tissue injury was severer in the model group, and the number of apoptotic cells in myocardial tissues was greater in the model group than that in other groups (p<0.05). The model group manifested higher expression levels of Caspase-3 and light chain 3 (LC3) than the ALDH2 group (p<0.05) but significantly lower expression levels of PINK1, Parkin and B-cell lymphoma-2 (Bcl-2) (p<0.05). In comparison with those in the model group, the protein expression levels of PINK1, Parkin and Bcl-2 in myocardial tissues were prominently higher in the ALDH2 group (p<0.05). ALDH2 can inhibit cardiomyocyte apoptosis in HF rats by activating the PINK1-Parkin signaling pathway-mediated mitophagy, which is conducive to the recovery of HF.

Correlation of Serum IL-17, VEGF, and Lactate Dehydrogenase (LDH) Levels with Prognosis of Gastric Cancer.

Objective: To investigate the correlation of serum interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and lactate dehydrogenase (LDH) levels with the prognosis of gastric cancer patients. Methods: From December 2018 to December 2020, 45 patients with gastric cancer treated in our hospital and 50 healthy individuals were assessed for eligibility and recruited. The eligible patients were assigned to an observation group, and the healthy subjects were assigned to a control group. Serum IL-17, LDH, and VEGF levels of the eligible participants were determined by the enzyme-linked immunosorbent assay (ELISA) and biochemical testing. The association of serum IL-7, LDH, and VEGF levels with their pathological characteristics was examined in the observation group. The correlation between serum IL-17 and VEGF was analyzed using the Pearson method, and regression models were established using COX proportional risk to explore the independent risk factors for gastric cancer. Results: Gastric cancer was associated with higher levels of IL-17, LDH, and VEGF versus a healthy status (P < 0.05). There was no significant difference in serum IL-17, LDH, and VEGF levels between the two groups of patients with different clinical characteristics (P > 0.05). Higher tumor TNM stages resulted in significantly higher levels of IL-17, LDH, and VEGF (P < 0.05). Serum IL-17 level was positively correlated with VEGF level (P < 0.05). Cox regression multifactorial analysis showed that serum IL-17, LDH, VEGF, and tumor TNM stages could be independent high-risk influencing factors for gastric cancer (P < 0.05). Serum IL-17 was positively correlated with VEGF levels in patients with gastric cancer. Conclusion: Serum IL-17, LDH, and VEGF levels in gastric cancer patients are closely correlated with the TNM stage and patients' prognosis, both of which show great potential as effective indicators for evaluating the prognosis of gastric cancer.

TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Effects of real-ambient PM2.5 exposure plus lipopolysaccharide on multiple organ damage in mice.

Background: The toxicological effects of fine particulate matter (PM2.5) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM2.5 plus LPS for 23 weeks in Linfen, a city with a high PM2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM2.5 plus LPS.