Effects of PM2.5 and high-fat diet on glucose and lipid metabolisms and role of MT-COX3 methylation in male rats.

Both fine particulate matter (PM2.5) and high-fat diet (HFD) can cause changes in glucose and lipid metabolisms; however, the mechanism of their combined effects on glucose and lipid metabolisms is still unclear. This study aimed to investigate the effects of PM2.5 and HFD co-exposure on glucose and lipid metabolisms and mitochondrial DNA methylation in Wistar rats. PM2.5 and HFD co-treatment led to an increase in fasting blood glucose levels, an alteration in glucose tolerance, and a decrease in high density lipoprotein cholesterol (HDL-C) levels in Wistar rats. In the homeostasis model assessment (HOMA), HOMA-insulin resistance (HOMA-IR) increased and HOMA-insulin sensitivity (HOMA-IS) and HOMA-ß cell function (HOMA-ß) decreased in rats co-exposed to PM2.5 and HFD. Additionally, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased, and interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA expressions were upregulated in the brown adipose tissue following PM2.5 and HFD co-exposure. Bisulfite pyrosequencing was used to detect the methylation levels of mitochondrially-encoded genes (MT-COX1, MT-COX2 and MT-COX3), and MT-COX3 was hypermethylated in the PM2.5 and HFD co-exposure group. Moreover, MT-COX3-Pos.2 mediated 36.41 % (95 % CI: -27.42, -0.75) of the total effect of PM2.5 and HFD exposure on HOMA-ß. Our study suggests that PM2.5 and HFD co-exposure led to changes in glucose and lipid metabolisms in rats, which may be related to oxidative stress and inflammatory responses, followed by mitochondrial stress leading to MT-COX3 hypermethylation. Moreover, MT-COX3-Pos.2 was found for the first time as a mediator in the impact of co-exposure to PM2.5 and HFD on ß-cell function. It could serve as a potential biomarker, offering fresh insights into the prevention and treatment of metabolic diseases.

Association of residential greenness, air pollution with adverse birth outcomes: Results from 61,762 mother­neonatal pairs in project ELEFANT (2011-2021).

BACKGROUND: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes. METHODS: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM2.5 exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA. Cox proportional hazard regression model was used to examine the association of residential greenness and air pollution exposure with risk of adverse birth outcomes. We performed mediation and modification effect analyses between greenness and air pollutant. RESULTS: We identified 61,762 mother­neonatal pairs in final analysis. For per 10 µg/m3 increase in PM2.5 concentration during entire pregnancy was associated with 19.8 % and 20.7 % increased risk of PTD and LGA. In contrast, we identified that an 0.1 unit increment in NDVI were associated with 24 %, 43 %, 26.5 %, and 39.5 % lower risk for PTD, LBW, LGA, and SGA, respectively. According to mediation analysis, NDVI mediated 7.70 % and 7.89 % of the associations between PM2.5 and PTD and LGA. Residential greenness could reduce the risk of PTD among mothers under 35 years old, living in rural areas, primigravidae and primiparity.. CONCLUSIONS: In summary, our results highlighted the potential of residential greenness to mitigate the risk of adverse birth outcomes, while also pointing to the adverse impact of PM2.5 on increased risk of multiple adverse birth outcomes (PTD and LGA). The significant mediation effect of NDVI emphasizes its potential as an important protective factor of PM2.5 exposure. Additionally, the identification of susceptible subgroups can inform targeted interventions to reduce adverse birth outcomes related to air pollution and lack of green spaces. Further research and understanding of these associations can contribute to better public health strategies aimed at promoting healthier pregnancies and birth outcomes.

Prenatal phthalate exposure and birth size: a systematic review and meta-analysis.

Phthalates are common endocrine disruptors. The placental barrier can be crossed by phthalates and may have a negative impact on the health of the fetus. However, the association between prenatal exposure to phthalates and birth size is still debatable. Here, we performed this meta-analysis to assess the relationship between prenatal phthalates exposure and birth size. Eighteen studies were finally included by searching PubMed, Embase, Scopus, Ovid, and Web of Science databases and standardized regression coefficients and standard errors were used to pool effect size. Our results showed that prenatal exposure to MMP (=-0.04, 95%CI: -0.08, -0.01) and MEP (=-0.01, 95%CI: -0.01, -0.002) was significantly associated with birth weight. However, no significant associations were identified for phthalate exposure with birth length, head circumference and chest circumference. Because the limiting of studies, more high-quality case-control studies or cohort studies are urgently needed to draw the best conclusions.

The Associations between Organophosphate Pesticides (OPs) and Respiratory Disease, Diabetes Mellitus, and Cardiovascular Disease: A Review and Meta-Analysis of Observational Studies.

Although some epidemiological studies have identified the associations between exposure to organophosphate pesticides (Ops) and respiratory diseases, diabetes mellitus (DM), and cardiovascular diseases (CVDs), controversial results still exist. In this review and meta-analysis, we aimed to investigate the overall pooled effect estimates and the possible mechanisms of the relationship between OP exposure and adverse health outcomes. In this study, Web of Science, PubMed, Embase, OVID, and the Cochrane Library were systematically searched until September 2022. Nineteen observational studies that focused on the general population or occupational populations examined the associations between OP exposure and respiratory diseases, DM, and CVD were included. Based on the overall pooled results, a significantly positive association was observed between OP exposure and respiratory diseases (OR: 1.12, 95% CI: 1.06-1.19). A significant link was also observed between various individual species of OP exposure and respiratory diseases, with an OR value of 1.11 (95% CI: 1.05-1.18). In particular, there was a significant association of OPs with wheezing and asthma, with OR values of 1.19 (95% CI: 1.08-1.31) and 1.13 (95% CI: 1.05-1.22), respectively. In addition, a significant association was also observed between OP exposure and DM (OR: 1.18, 95% CI: 1.07-1.29). However, no significant association was observed between OP exposure and CVD (OR: 1.00, 95% CI: 0.94-1.05). Exposure to OPs was associated with a significantly increased risk of respiratory diseases and DM, but there was no evidence of a significant association between OP exposure and CVD. Considering the moderate strength of the results, further evidence is needed to confirm these associations.

Palladium-Catalyzed Tandem C(sp3)-H Insertion Cyclization of 2-(2-Vinylarene)acetonitriles with Isocyanides to Access Naphthalen-2-amines.

A Pd-catalyzed cyclization reaction of 2-(2-vinylarene)acetonitriles and isocyanides has been documented. Various naphthalen-2-amines were obtained in moderate to good yields under mild conditions. The in vitro cytotoxicity of all products was evaluated by MTT assay against seven human cancer cell lines. The results indicated that compounds 3ea, 3ma, and 3ob exhibited effective anticancer activities against the tested cancer cells.

Enhanced antitumor and anti-metastasis by VEGFR2-targeted doxorubicin immunoliposome synergy with NK cell activation.

Liposomal doxorubicin exhibits stronger drug accumulation at the tumor site due to the Enhanced Permeability and Retention (EPR) effect. However, the prognosis for the patient is poor due to this drug's lack of targeting and tumor metastasis during treatment. Vascular epidermal growth factor receptor (VEGFR2) plays an important role in angiogenesis and cancer metastasis. To enhance antitumor efficacy of PEGylated liposomal doxorubicin, we constructed a VEGFR2-targeted and doxorubicin-loaded immunoliposome (Lipo-DOX-C00) by conjugating a VEGFR2-specific, single chain antibody fragment to DSPE-PEG2000-MAL, and then we inserted the antibody-conjugated polymer into liposomal doxorubicin (Lipo-DOX). The immunoliposome was formed uniformly with high affinity for VEGFR2. In vitro, Lipo-DOX-C00 enhanced doxorubicin internalization into LLC and 4T1 cells compared with non-conjugated, liposomal doxorubicin. In vivo, Lipo-DOX-C00 delivered DOX to tumor tissues effectively, which exhibited an improved antitumor and anti-metastasis efficacy in both LLC subcutaneous tumor models and 4T1 tumor models. In addition, the combined therapy of a VEGFR2-MICA bispecific antibody (JZC01) and Lipo-DOX-C00 achieved enhanced inhibition of cancer growth and metastasis due to activation of the immune system. Our study provides a promising approach to clinical application of liposomal doxorubicin.

Green space exposure on depression and anxiety outcomes: A meta-analysis.

BACKGROUND: The development of urbanization has led to emerging mental health issues. Green space was becoming increasingly important for mental health. Previous studies have demonstrated the value of green space for a variety of outcomes connected to mental health. However, uncertainty remains regarding the association between green spaces and the risk of depression and anxiety outcomes. This study aimed to integrate present evidence from observational studies to define the association of exposure to green space with depression and anxiety. METHODS: A thorough electronic search of PubMed, Web of Science and Embase database was performed. We transformed the odds ratio (OR) of different green increments into per 0.1 unit increase in normalized difference vegetation index (NDVI) and per 10% increase in percentage of green space. Cochrane's Q and I2 statistics were used to assess study heterogeneity, and random-effects models were employed to calculate combined effect estimation OR with 95% confidence intervals (CIs). Pooled analysis was completed using Stata 15.0. RESULTS: According to this meta-analysis, a 10% increase in the proportion of green space was linked to a lower risk of depression (merged OR (95% CI) = 0.963 (0.948, 0.979)) and anxiety (merged OR (95% CI) = 0.938 (0.858, 1.025)) and a 0.1 unit increase in NDVI was linked to a lower risk of depression (merged OR (95% CI) = 0.931 (0.887, 0.977)). CONCLUSIONS: Results of this meta-analysis supported improving green space exposure in preventing depression and anxiety. Higher green space exposure might be helpful for depression and anxiety disorders. Therefore, improving or preserving green space should be regarded as a promising intervention for public health.

Circulating Pulmonary-Originated Epithelial Biomarkers for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Previous studies have found several biomarkers for acute respiratory distress syndrome (ARDS), but the accuracy of most biomarkers is still in doubt due to the occurrence of other comorbidities. In this systematic review and meta-analysis, we aimed to explore ideal ARDS biomarkers which can reflect pathophysiology features precisely and better identify at-risk patients and predict mortality. Web of Science, PubMed, Embase, OVID, and the Cochrane Library were systematically searched for studies assessing the reliability of pulmonary-originated epithelial proteins in ARDS. A total of 32 studies appeared eligible for meta-analysis, including 2654 ARDS/ALI patients in this study. In the at-risk patients' identification group, the highest pooled effect size was observed in Krebs von den Lungren-6 (KL-6) (SMD: 1.17 [95% CI: 0.55, 1.79]), followed by club cell proteins 16 (CC16) (SMD: 0.74 [95% CI: 0.01, 1.46]), and surfactant proteins-D (SP-D) (SMD: 0.71 [95% CI: 0.57, 0.84]). For the mortality prediction group, CC16 exhibited the largest effect size with SMD of 0.92 (95% CI: 0.42, 1.43). Meanwhile, the summary receiver operating characteristic (SROC) of CC16 for ARDS diagnosis reached an AUC of 0.80 (95% CI: 0.76, 0.83). In conclusion, this study provides a ranking system for pulmonary-originated epithelial biomarkers according to their association with distinguishing at-risk patients and predicting mortality. In addition, the study provides evidence for the advantage of biomarkers over traditional diagnostic criteria. The performance of biomarkers may help to clinically improve the ARDS diagnosis and mortality prediction.

Exposure of ambient PM2.5 during gametogenesis period affects the birth outcome: Results from the project ELEFANT.

Various environmental and behavioural factors influence neonatal health. Gamete formation (gametogenesis) is a crucial period which affects embryo development and neonatal health and ambient air pollution exposure at this stage may lead to an adverse birth outcome. Previous epidemiological and toxicological research demonstrated a strong association between maternal ambient air pollution exposure and adverse birth outcomes. However, the joint exposure-outcome of paternal exposure (76 days before the last menstruation and 14 days after the last menstruation) and maternal exposure (14 days after the last menstruation) when exploring the mechanism of the influence of air pollutants on pregnancy outcome and neonatal health remains unexplored. Here, in the Project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT), we collected the data of 10,960 singleton pregnant women with 24-42 completed gestational weeks and included them in this study. A multinominal logistic regression model was applied to investigate the association between adverse birth outcomes and ambient PM2.5 exposure levels during spermatogenesis and oogenesis. Results from the binary classification of ambient PM2.5 exposure showed that the risk of abnormal birthweight was significantly greater when ambient PM2.5 exposure was both higher during spermatogenesis and oogenesis, with RRs of 1.86 (95% CI: 1.02, 3.39). The risk of macrosomia (RR: 1.88 (95% CI: 1.13, 3.12)) increased significantly when ambient PM2.5 levels were higher during spermatogenesis. Primiparity and primigravity are more likely to be influenced by higher ambient PM2.5 levels during spermatogenesis. In conclusion, more attention should be paid to higher exposure level of ambient PM2.5 during spermatogenesis.