Genetic influence on vascular smooth muscle cell apoptosis.

Vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis play important roles in many physiological processes and pathological conditions. To identify genetic influences on VSMC behavior, we measured these traits and undertook genome-wide association studies in primary umbilical artery-derived VSMCs from >2000 individuals. Although there were no genome-wide significant associations for VSMC proliferation or migration, genetic variants at two genomic loci (7p15.3 and 7q32.3) showed highly significant associations with VSMC apoptosis (P = 1.95 × 10-13 and P = 7.47 × 10-9, respectively). The lead variant at the 7p51.3 locus was associated with increased expression of the GSDME and PALS2 genes in VSMCs. Knockdown of GSDME or PALS2 in VSMCs attenuated apoptotic cell death. A protein co-immunoprecipitation assay indicated that GSDME complexed with PALS2. PALS2 knockdown attenuated activated caspase-3 and GSDME fragmentation, whilst GSDME knockdown also reduced activated caspase-3. These findings provide new insights into the genetic regulation of VSMC apoptosis, with potential utility for therapeutic development.

Allele-Specific Epigenetic Regulation of FURIN Expression at a Coronary Artery Disease Susceptibility Locus.

Genome-wide association studies have revealed an association between the genetic variant rs17514846 in the FURIN gene and coronary artery disease. We investigated the mechanism through which rs17514846 modulates FURIN expression. An analysis of isogenic monocytic cell lines showed that the cells of the rs17514846 A/A genotype expressed higher levels of FURIN than cells of the C/C genotype. Pyrosequencing showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine increased FURIN expression. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected DNA-protein complex bands that were altered by an anti-MeCP2 antibody. A chromatin immunoprecipitation assay with the anti-MeCP2 antibody showed an enrichment of the DNA sequence containing the rs17514846 site. siRNA-mediated knockdown of MeCP2 caused an increase in FURIN expression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor. The results of our study suggest that DNA methylation inhibits FURIN expression and that the coronary artery disease-predisposing variant rs17514846 modulates FURIN expression and monocyte migration via an allele-specific effect on DNA methylation.

The FES Gene at the 15q26 Coronary-Artery-Disease Locus Inhibits Atherosclerosis.

BACKGROUND: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES. There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.

Development and Validation of a Nomogram for Predicting Postoperative Delirium in Patients With Elderly Hip Fracture Based on Data Collected on Admission.

Delirium is a common postoperative complication in elderly hip fracture patients that seriously affects patients' lives and health, and early delirium risk prediction, and targeted measures can significantly reduce the incidence of delirium. The purpose of this study was to develop and validate a nomogram for the prediction of postoperative delirium (POD) in elderly hip fracture patients. A total of 328 elderly patients with hip fractures enrolled retrospectively in department 1 of our hospital were randomly divided into the training set (n = 230) and the internal validation set (n = 98). The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature variable selection, and multivariate logistic regression with a backward stepwise method was used to construct a nomogram in the training set. The discrimination efficacy and calibration efficacy of the nomogram were evaluated through the receiver operating characteristic (ROC) curve and calibration curve, respectively. The clinical usefulness was estimated through decision curve analysis (DCA) and clinical impact curve (CIC) analysis. Another validation set from department 2 of our hospital, containing 76 elderly patients with hip fractures, was used for external validation of the nomogram. A total of 43 (13.1%) and 12 (15.8%) patients had POD in department 1 and department 2, respectively. The nomogram was constructed by three predictors, including dementia, chronic obstructive pulmonary disease (COPD), and albumin level. The nomogram showed good discrimination efficacy and calibration efficacy, with the AUC of 0.791 (95% CI, 0.708-0.873), 0.820 (95% CI, 0.676-0.964), and 0.841 (95% CI, 0.717-0.966) in the training set, the internal validation set, and the external validation set, respectively. Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. The nomogram constructed by dementia, COPD, and albumin level can be conveniently used to predict POD in patients with elderly hip fractures.

Temporal and Spatial Evolution of Eichmann Lake Wetland in Aksu River Basin and Its Response to Ecological Water Supply.

Timely understanding and quantitative analysis of the changing trend in natural ecosystems in arid and semi-arid areas and their response to the ecological water supply process are of great significance for maintaining the health of oasis ecosystems. Taking the Eichmann Lake wetland of the Aksu River Basin in Xinjiang as the research area, the temporal-spatial distribution characteristics of the lake and the response of ecological water in recent years were studied based on remote sensing images and monitoring data. The results show that: (1) The water surface area of Eichmann Lake is shrinking, from 61.57 km2 in 1996 to 27.76 km2 in 2020. The changes in water surface area have experienced three stages: rapid decline, slow decline, and slow recovery. After the ecological water supply, the water surface area has obvious seasonal changes with hysteresis; (2) In areas with a low average water level, the ecological water supply has a significant impact on the groundwater level. The higher the water supply is, the higher the groundwater level will be. There is a significant lag effect between the change in the groundwater level and the response of the ecological water supply, which is 1-2 months; (3) The response characteristics of different natural vegetation to the ecological water supply were different in interannual, seasonal, and spatial contexts. The response of Populus euphratica to the ecological water supply is obvious, and its growth is the best within the range of 100-500 m from the water supply outlet. This research can provide the basis for the rational allocation of the Aksu River Basin's water resources, and also act as a valuable reference for the restoration and reconstruction of surrounding vegetation in the Aksu River irrigation area.

A functional extracellular matrix biomaterial enriched with VEGFA and bFGF as vehicle of human umbilical cord mesenchymal stem cells in skin wound healing.

The construction of microvascular network is one of the greatest challenges for tissue engineering and cell therapy. Endothelial cells are essential for the construction of network of blood vessels. However, their application meets challenges in clinic due to the limited resource of autologous endothelium. Mesenchymal stem cells can effectively promote the angiogenesis in ischemic tissues for their abilities of endothelial differentiation and paracrine, and abundant sources. Extracellular matrix (ECM) has been widely used as an ideal biomaterial to mimic cellular microenvironment for tissue engineering due to its merits of neutrality, good biocompatibility, degradability, and controllability. In this study, a functional cell derived ECM biomaterial enriched with VEGFA and bFGF by expressing the collagen-binding domain fused factor genes in host cells was prepared. This material could induce endothelial differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs) and promote angiogenesis, which may improve the healing effect of skin injury. Our research not only provides a functional ECM material to inducing angiogenesis by inducing endothelial differentiation of hUCMSCs, but also shed light on the ubiquitous approaches to endow ECM materials different functions by enriching different factors. This study will benefit tissue engineering and regenerative medicine researches.

Is satellite Sun-Induced Chlorophyll Fluorescence more indicative than vegetation indices under drought condition?

Droughts represent one of the most severe abiotic stress factors that could result in great crop yield loss. Numerous vegetation indices have been proposed for monitoring the vegetation condition under stress and assessing drought impacts on yield loss. However, the understanding and comparison between traditional vegetation indices (VIs) and the newly emerging satellite Sun-Induced Chlorophyll Fluorescence (SIF) for monitoring vegetation condition is still limited especially under drought stress and at multiple spatial scales. In this study, the potential of satellite observation SIF for monitoring corn response to drought was investigated based on the 2012 drought in the US Corn Belt. The standardized precipitation evapotranspiration index (SPEI) was used here to quantify drought. We found that all SPEI were above -1, except for July (-1.27), August (-1.39) and September (-1.14) in 2012, indicating the severity of this drought. We examined the relationship between satellite measurements of SIF, SIFyield, VIs (e.g., NDVI and EVI) and SPEI. Results indicated that SIFyield was sensitive to drought and SIF captured the stress more accurately both at the regional and state scales for the US Corn Belt. Quantitatively, SIFyield had a high correlation with SPEI (r = 0.987, p < 0.05) over the entire Corn Belt, and it indicated losses in response to drought approximately one month earlier than SIF/NDVI/EVI. Furthermore, our results demonstrated that SIF could be trusted as an effective indicator to study the relationship between GPP (R2 ≥ 0.8664, p < 0.01) under drought conditions across the Corn Belt. This study highlighted the advantage of using satellite SIF observations to monitor the drought stress on crop growth especially GPP at regional scale.

Detection and Difference Analysis of the Enzyme Activity of Colloidal Gold Nanoparticles With Negatively Charged Surfaces Prepared by Different Reducing Agents.

Nanozymes are particles with diameters in the range of 1-100 nm, which has been widely studied due to their biological enzyme-like properties and stability that natural enzymes do not have. In this study, several reducing agents with different structures (catechol (Cc), hydroquinone (Hq), resorcinol (Rs), vitamin C (Vc), pyrogallic acid (Ga), sodium citrate (Sc), sodium malate (Sm), and sodium tartrate (St)) were used to prepare colloidal gold with a negative charge and similar particle size by controlling the temperature and pH. The affinity analysis of the substrate H2O2 and TMB showed that the order of activities of colloidal gold Nanozymes prepared by different reducing agents was Cc, Hq, Rs, Vc, Ga, Sc, Sm, St. It was also found that the enzyme activity of colloidal gold reduced by benzene rings is higher than that of the colloidal gold enzyme reduced by linear chains. Finally, we discussed the activity of the colloidal gold peroxidase based on the number and position of isomers and functional groups; and demonstrated that the nanozymes activity is affected by the surface activity of colloidal gold, the elimination of hydroxyl radicals and the TMB binding efficiency.

Prenatal smoke exposure dysregulates lung epithelial cell differentiation in mouse offspring: role for AREG-induced EGFR signaling.

Prenatal smoke exposure is a risk factor for impaired lung development in children. Recent studies have indicated that amphiregulin (AREG), which is a ligand of the epidermal growth factor receptor (EGFR), has a regulatory role in airway epithelial cell differentiation. In this study, we investigated the effect of prenatal smoke exposure on lung epithelial cell differentiation and linked this with AREG-EGFR signaling in 1-day-old mouse offspring. Bronchial and alveolar epithelial cell differentiations were assessed by immunohistochemistry. Areg, epidermal growth factor (Egf), and mRNA expressions of specific markers for bronchial and alveolar epithelial cells were assessed by RT-qPCR. The results in neonatal lungs were validated in an AREG-treated three-dimensional mouse lung organoid model. We found that prenatal smoke exposure reduced the number of ciliated cells and the expression of the cilia-related transcription factor Foxj1, whereas it resulted in higher expression of mucus-related transcription factors Spdef and Foxm1 in the lung. Moreover, prenatally smoke-exposed offspring had higher numbers of alveolar epithelial type II cells (AECII) and lower expression of the AECI-related Pdpn and Gramd2 markers. This was accompanied by higher expression of Areg and lower expression of Egf in prenatally smoke-exposed offspring. In bronchial organoids, AREG treatment resulted in fewer ciliated cells and more basal cells when compared with non-treated bronchiolar organoids. In alveolar organoids, AREG treatment led to more AECII cells than non-treated AECII cells. Taken together, the observed impaired bronchial and alveolar cell development in prenatally smoke-exposed neonatal offspring may be induced by increased AREG-EGFR signaling.

Comprehensive analysis of the lncRNA-associated ceRNA network identifies neuroinflammation biomarkers for Alzheimer's disease.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in Alzheimer's disease (AD). In this study, we constructed an AD-derived lncRNA-associated ceRNA network (LncACeNET) based on the ceRNA hypothesis and co-expressed correlation analysis of RNAs (miRNAs, mRNAs and lncRNAs) from AD patients. Based on this network, we preliminarily identified new potential AD biomarkers including hsa-miR-155-5p, CERS6-AS1, and CTB-89H12.4. The functional enrichment analysis demonstrated that these inferred biomarkers were significantly correlated with AD-related biological processes such as neuron projection development and neuron projection morphogenesis. Notably, lncRNA CTB-89H12.4 is significantly associated with "calcium ion-regulated exocytosis of neurotransmitter", "chemical synaptic transmission", "presynaptic membrane assembly", "receptor localization to synapse", and "learning". This indicates the important role of CTB-89H12.4 as a promising target for AD therapy. Subsequently, we used the computational pipeline DTINet and discovered 19 lines of probable therapeutic relationships between FDA-approved drugs and CTB-89H12.4, which offered a new avenue to repurpose existing FDA-approved drugs for AD indication. Our study provides a new landscape for LncACeNET in AD, and will benefit mechanism study and new drug development for AD.

Ultrasensitive dual-color rapid lateral flow immunoassay via gold nanoparticles with two different morphologies for the serodiagnosis of human brucellosis.

Lateral flow immunoassays (LFIAs) are popular because they are rapid, convenient, stable, low cost, and easy to read. However, conventional LFIAs based on gold nanoparticles lack sensitivity, which hinders their widespread use. Here, we prepared durian-like gold nanoparticles (GNDs) and labeled them with staphylococcal protein A to detect brucella antibody. Then, the analytical performances of GNDs and gold nanospheres (GNSs) with the same diameter were compared. It was found that the sensitivity of GNDs was five to ten times higher than that of GNSs. The nonspherical morphologies of the nanoparticles greatly increased the sensitivity of the LFIA. On the basis of GNDs and GNSs, we developed an ultrasensitive dual-color brucellosis LFIA. GNSs labeled with streptavidin were used to demonstrate the control line. This dual-color LFIA had a diagnostic sensitivity and specificity of 100%. Human standard Brucella-positive serum (containing brucella antibody at 4000 IU/mL) could be detected in this system even for a dilution factor of 10-5. The detection limit was 0.04 IU/mL. This is two orders of magnitude better than conventional LFIA strips (detection limit 4 IU/mL). This dual-color LFIA contains all components of a conventional LFIA with no additional processing steps or reagents. It can detect antibodies in serum, plasma, and even whole blood without sample pretreatment or blood filtration pads. Both types of nanoparticles were synthesized in a simple and low-cost manner. This suggests that it will have utility for the early diagnosis of brucellosis and other diseases. Graphical abstract.

Effects of Exposure to Bisphenol A during Pregnancy on the Pup Testis Function.

Testosterone plays an important prenatal role in male testis development. Bisphenol A (BPA) exposure during pregnancy affects testosterone levels and germ cell apoptosis of male pups, but little information is available for the mechanism. The aim of the present study was to investigate the mechanism by which BPA alters testosterone levels and germ cell apoptosis. Pregnant female C57BL/6J mice, throughout gestation, had access to drinking water containing BPA at 5 and 50 µg/mL. Male pups were euthanized on postnatal days (PNDs) 1, 14, and 35. Relative to control, BPA exposure at 5 and 50 µg/ml decreased testosterone level, as measured by chemiluminescent immunoassay, on PND14. Real-time PCR indicated mRNA levels for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 3-ß-hydroxysteroid dehydrogenase/△-5-4 isomerase (3ß-HSD) were significantly lower in the BPA pups compared to control. Additionally, BPA increased the percentage of TUNEL-positive seminiferous tubules, decreased the mRNA level of Bcl-2, and increased Bax expression, indicative of increased apoptosis. These results suggest that BPA exposure in utero decreases the testosterone concentration by decreasing steroidogenic enzymes (StAR, CYP11A1, and 3ß-HSD). Furthermore, BPA exposure increases the apoptosis of germ cells, which is associated with proapoptotic changes in the levels of Bcl-2 and Bax.

Loop-mediated isothermal amplification-lateral-flow dipstick (LAMP-LFD) to detect Mycoplasma ovipneumoniae.

In order to establish a rapid detection method for Mycoplasma ovipneumoniae, this study used the loop-mediated isothermal amplification (LAMP) technique to carry out nucleic acid amplification and chromatographic visualization via a lateral flow dipstick (LFD) assay. The M. ovipneumoniae elongation factor TU gene (EF-TU) was detected using a set of specific primers designed for the EF-TU gene, and the EF-TU FIP was detected by biotin labeling, which was used in the LAMP amplification reaction. The digoxin-labeled probe specifically hybridized with LAMP products, which were visually detected by LFD. Here, we established the M. ovipneumoniae LAMP-LFD rapid detection method and tested the specificity, sensitivity, and clinical application of this method. Results showed that the optimized LAMP performed at 60 °C for 60 min, and LFD can specifically and visually detect M. ovipneumoniae with a minimum detectable concentration at 1.0 × 102 CFU/mL. The sensitivity of LAMP-LFD was 1000 times that of the conventional PCR detection methods, and the clinical lung tissue detection rate was 86% of 50 suspected sheep infected with M. ovipneumoniae. In conclusion, LAMP-LFD was established in this study to detect M. ovipneumoniae, a method that was highly specific, sensitive, and easy to operate, and provides a new method for the prevention and diagnosis of M. ovipneumoniae infection.

Improving microwave-assisted hydrothermal degradation of PCDD/Fs in fly ash with added Na2HPO4 and water-washing pretreatment.

In this work, microwave-assisted hydrothermal process is applied to the PCDD/F degradation of municipal solid waste incineration (MSWI) fly ash. The effects of water-washing pretreatment and the Na2HPO4 reagent on the degradation efficiency of PCDD/Fs are investigated. The PCDD/F content in MSWI fly ash is detected by high-resolution gas chromatography-mass spectrometry (HRGC/MS). The experimental results show that the efficiency of total PCDD/F degradation increases from 60.6% to 83.3% after water-washing pretreatment, with 5 wt % Na2HPO4 added for 2 h of microwave heating at 220 °C. With more Na2HPO4 (10 wt %), the degradation efficiency of PCDD/Fs reaches 91.8%, and remarkably, the WHO-TEQ is as low as 0.255 ng g-1. Analysis of the degradation pathway of PCDD/Fs indicates that a chlorination reaction happens during the microwave-assisted hydrothermal process, as do dechlorination and destruction reactions. Water-washing effectively weakens the chlorination reaction for the decrease of chlorine in fly ash, which contributes to PCDD/F degradation. The reagent Na2HPO4 has a greater effect on the dechlorination of high-chlorinated congeners. Furthermore, the results indicate that the removal efficiency of PCDDs is higher than that of PCDFs under microwave conditions. Several linear correlations between indicative congener content and I/WHO-TEQ values are summarized. Overall, microwave-assisted hydrothermal process is a promising disposal method and should receive further study for large-scale application.

Extraction of Genomic DNA via Superparamagnetic Fe3O4 Magnetic Colloidal Nanocrystal Clusters.

We herein describe a solvothermal method for preparing superparamagnetic Fe3O4 magnetic colloidal nanocrystal clusters with an average diameter of 195 nm. The Fe3O4 magnetic colloidal nanocrystal clusters were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and other methods. The Fe3O4 magnetic colloidal nanocrystal clusters were used to extract genomic DNA from fresh blood, Gram-negative bacteria, Gram-positive bacteria and frozen blood. Results showed that the genomic DNA integrity, purity and yield extracted via this universal method were satisfactory. This method is rapid, simple and does not use protease K or toxic compounds. This method lays the foundation for future research and nucleic acid extraction techniques.

Increased memory T cell populations in Pb-exposed children from an e-waste-recycling area.

Chronic exposure to heavy metals could affect cell-mediated immunity. The aim of this study was to explore the status of memory T cell development in preschool children from an e-waste recycling area. Blood lead (Pb) levels, peripheral T cell subpopulations, and serum levels of cytokines (IL-2/IL-7/IL-15), relevant to generation and homeostasis of memory T cells were evaluated in preschool children from Guiyu (e-waste-exposed group) and Haojiang (reference group). The correlations between blood Pb levels and percentages of memory T cell subpopulations were also evaluated. Guiyu children had higher blood Pb levels and increased percentages of CD4+ central memory T cells and CD8+ central memory T cells than in the Haojiang group. Moreover, blood Pb levels were positively associated with the percentages of CD4+ central memory T cells. In contrast, Pb exposure contributed marginally in the change of percentages of CD8+ central memory T cells in children. There was no significant difference in the serum cytokine levels between the e-waste-exposed and reference children. Taken together, preschool children from an e-waste recycling area suffer from relatively higher levels of Pb exposure, which might facilitate the development of CD4+ central memory T cells in these children.

Alteration of the number and percentage of innate immune cells in preschool children from an e-waste recycling area.

Heavy metal lead (Pb) and cadmium (Cd) are widespread environmental contaminants and exert detrimental effects on the immune system. We evaluated the association between Pb/Cd exposures and innate immune cells in children from an electronic waste (e-waste) recycling area. A total number of 294 preschool children were recruited, including 153 children from Guiyu (e-waste exposed group), and 141 from Haojiang (reference group). Pb and Cd levels in peripheral blood were measured by graphite furnace atomic absorption spectrophotometer, NK cell percentages were detected by flow cytometer, and other innate immune cells including monocytes, eosinophils, neutrophils and basophils were immediately measured by automated hematology analyzer. Results showed children in Guiyu had significantly higher Pb and Cd levels than in reference group. Absolute counts of monocytes, eosinophils, neutrophils and basophils, as well as percentages of eosinophils and neutrophils were significantly higher in the Guiyu group. In contrast, NK cell percentages were significantly lower in Guiyu group. Pb elicited significant escalation in counts of monocytes, eosinophils and basophils, as well as percentages of monocytes, but decline in percentages of neutrophils in different quintiles with respect to the first quintile of Pb concentrations. Cd induced significant increase in counts and percentages of neutrophils in the highest quintile compared with the first quintile of Cd concentrations. We concluded alteration of the number and percentage of innate immune cells are linked to higher levels of Pb and Cd, which indicates Pb and Cd exposures might affect the innate and adaptive immune response in Guiyu children.

BAMBI inhibits inflammation through the activation of autophagy in experimental spinal cord injury.

Autophagy plays an important role in the progression of spinal cord injury (SCI). In this study, we aimed to examine the effects and potential mechanisms of action of BMP and activin membrane-bound inhibitor (BAMBI) in the progression of SCI. A rat model of SCI was established and the rats were injected with pLentiH1-BAMBI shRNA and pAd-BAMBI in the gray and white matter of the spinal cord at T8. After 14 days, motor function evaluation was measured according to the Basso Beattie Bresnahan (BBB) method and the number of motor neuron cell accounts in the anterior horns was measured by Nissl staining. The protein expression of levels light chain 3B (LC3B), Beclin 1, Bim and p62 were measured by western blot analysis. The concentrations of interleukin (IL)-1ß, IL-6 and IL-10 were measured by ELISA. The results revealed that BAMBI expression was significantly decreased in the rats with SCI. The BBB scores and the number of motor neuron cell accounts in the anterior horns were significantly decreased in the pLentiH1-BAMBI shRNA injection group, and were increased in the pAd-BAMBI injection group, suggesting a neuroprotective effect of BAMBI in SCI. Moreover, the increased expression levels of LC3B and Beclin 1, and the decreased expression of Bim and p62 indicated that autophagy was significantly induced in the pAd-BAMBI injection group. Moreover, the overexpression of BAMBI also decreased the expression of transforming growth factor-ß (TGF-ß) and mammalian target of rapamycin (mTOR), and decreased the concentrations of IL-1ß, IL-6 and IL-10. These results indicate that BAMBI plays a neuroprotective role by decreasing inflammation and activating autophagy in rats with SCI.

Early-life Exposure to Widespread Environmental Toxicants and Health Risk: A Focus on the Immune and Respiratory Systems.

Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life.

The role of the PM2.5-associated metals in pathogenesis of child Mycoplasma Pneumoniae infections: a systematic review.

The peak occurrence of Mycoplasma pneumoniae (M. pneumoniae) infections in childhood and haze episodes is concurrent. Together, the prevalence of macrolide-resistant M. pneumoniae varies among countries might also be related to the concentration of ambient fine particulate mass (aerodynamic diameter ≤2.5 µm, PM2.5). Numerous cohort studies have identified consistent associations between ambient PM2.5 and cardiorespiratory morbidity and mortality. PM2.5 is a carrier of the heavy metals. The relationship between PM2.5-associated metals and M. pneumoniae infections in childhood has been increasingly drawing public attention. First, we reviewed original articles and review papers in Pubmed and Web of Science regarding M. pneumoniae and PM2.5-associated metal and analyzed the structural basis of PM2.5-associated metal interaction with M. pneumoniae. Then, the possible mechanisms of action between them were conjectured. Mechanisms of oxidative stress induction and modulation of the host immune system and inflammatory responses via Toll-like receptors (TLRs) and/or the nuclear factor-kappa B (NF-κB) pathway are postulated to be the result of PM2.5-associated metal complex interaction with M. pneumoniae. In addition, a heavy metal effect on M. pneumoniae-expressed community-acquired respiratory distress syndrome (CARDS) toxin, and activation of the aryl hydrocarbon receptor (AhR) and TLRs to induce the differentiation of T helper (Th) cells are also regarded as important reasons for the influence of the heavy metals on the severity of M. pneumoniae pneumonia and the initial onset and exacerbation of M. pneumoniae associated asthma. PM2.5-associated metals via complex mechanisms can exert a great impact on the host through interaction with M. pneumoniae.