Nicotine suppresses crystalline silica-induced astrocyte activation and neuronal death by inhibiting NF-κB in the mouse hippocampus.

AIMS: Exposure to crystalline silica (CS) in occupational settings induces chronic inflammation in the respiratory system and, potentially, the brain. Some workers are frequently concurrently exposed to both CS and nicotine. Here, we explored the impact of nicotine on CS-induced neuroinflammation in the mouse hippocampus. METHODS: In this study, we established double-exposed models of CS and nicotine in C57BL/6 mice. To assess depression-like behavior, experiments were conducted at 3, 6, and 9 weeks. Serum inflammatory factors were analyzed by ELISA. Hippocampus was collected for RNA sequencing analysis and examining the gene expression patterns linked to inflammation and cell death. Microglia and astrocyte activation and hippocampal neuronal death were assessed using immunohistochemistry and immunofluorescence staining. Western blotting was used to analyze the NF-κB expression level. RESULTS: Mice exposed to CS for 3 weeks showed signs of depression. This was accompanied by elevated IL-6 in blood, destruction of the blood-brain barrier, and activation of astrocytes caused by an increased NF-κB expression in the CA1 area of the hippocampus. The elevated levels of astrocyte-derived Lcn2 and upregulated genes related to inflammation led to higher neuronal mortality. Moreover, nicotine mitigated the NF-κB expression, astrocyte activation, and neuronal death, thereby ameliorating the associated symptoms. CONCLUSION: Silica exposure induces neuroinflammation and neuronal death in the mouse hippocampal CA1 region and depressive behavior. However, nicotine inhibits CS-induced neuroinflammation and neuronal apoptosis, alleviating depressive-like behaviors in mice.

Anti-inflammatory activity of a new lactone isolated from the leaves of Ardisia crenata Sims.

One new lactone (1) named Ardisicreolide C, together with three saponin compounds, Ardisiacrispin B (2), Ardisicrenoside A (3), Ardisiacrispin A (4) were isolated and identified from the leaves of Ardisia crenata Sims. The structures of 1-4 were elucidated by 1D, 2D-NMR and HR-MS spectra and together with the published data. In view of structures with lactone moieties showed good anti-inflammatory activity, the anti-inflammatory effects of Ardisicreolide C on LPS-induced RAW264.7 cells were evaluated by enzyme linked immunosorbent assay (ELISA) method. As a result, Ardisicreolide C could reduce release of nitric oxide (NO), tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 4 (IL-4) and interleukin 10 (IL-10) of the cell supernatant to exert anti-inflammatory activity. This indicates that the leaves as non-medicinal parts of Ardisia crenata Sims contain compounds with good anti-inflammatory activity, which provides a new direction for the discovery of anti-inflammatory drugs.

Comparison of the shear rebond strength of zirconia brackets treated with different Er:YAG laser energies.

This study aimed to identify the optimal technological parameters for rebonding zirconia brackets treated using an erbium-doped yttrium aluminum garnet (Er:YAG) laser. Er:YAG lasers with varying energies were compared with the flaming and sandblasting treatment methods. Detached zirconia brackets were treated and evaluated for shear rebond strength, bracket bottom-plate morphology, position, and depth of microleakage. They were then treated for rebonding using flaming, sandblasting, or an Er:YAG laser set at 250-mJ, 300-mJ, 350-mJ energy. Their shear rebond strength were measured using microforce tester. The topography of the treated bottom plates were observed using scanning electron microscopy. A confocal laser scanning microscope was used to measure the depth of the joint and gingival-side microleakage at the bracket-adhesive (B-A) and enamel-adhesive interfaces. With 300 mJ Er:YAG laser treatment, the detached zirconia brackets can obtain good rebonding strength and minimize the shape change of bracket bottom plates; the adhesion of the B-A interface is better than other methods.

Nicotine exposure exacerbates silica-induced pulmonary fibrosis via STAT3-BDNF-TrkB-mediated epithelial-mesenchymal transition in alveolar type II cells.

The addictive substance nicotine, found in cigarettes and some e-cigarettes, plays a vital role in pro-inflammatory and fibrotic processes. However, the part played by nicotine in the progression of silica-induced pulmonary fibrosis is poorly understood. We used mice exposed to both silica and nicotine to investigate whether nicotine synergizes with silica particles to worsen lung fibrosis. The results revealed that nicotine accelerated the development of pulmonary fibrosis in silica-injured mice by activating STAT3-BDNF-TrkB signalling. Mice with a history of exposure to nicotine showed an increase in Fgf7 expression and alveolar type II cell proliferation if they were also exposed to silica. However, newborn AT2 cells could not regenerate the alveolar structure and release pro-fibrotic factor IL-33. Moreover, activated TrkB induced the expression of p-AKT, which promotes the expression of epithelial-mesenchymal transcription factor Twist, but no Snail. In vitro assessment confirmed activation of the STAT3-BDNF-TrkB pathway in AT2 cells, exposed to nicotine plus silica. In addition, TrkB inhibitor K252a downregulated p-TrkB and the downstream p-AKT and restricted the epithelial-mesenchymal transition caused by nicotine plus silica. In conclusion, nicotine activates the STAT3-BDNF-TrkB pathway, which promotes epithelial-mesenchymal transition and exacerbates pulmonary fibrosis in mice with combined exposure to silica particles and nicotine.

VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice.

Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1ß, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis.

Effects of different frequencies of Er:YAG laser on the bonding properties of zirconia ceramic.

The effects of Er:YAG laser with different frequencies on zirconia ceramic's bonding properties were studied. In total, 42 Y-TZP (yttrium-stabilized tetragonal zirconia polycrystals, UPCERA ST) with 3 mm × 3 mm × 2 mm divided into 6 groups (n = 7): control (C), sandblasting (SB), and Er:YAG laser (A1-A4), which the frequencies correspond to 5 Hz, 10 Hz, 15 Hz, and 20 Hz, IPS e.max Press ceramics were B. Scanning electron microscope (SEM) images were recorded. The ceramics were bonded to enamel from extracted teeth. After being constantly stored at 37 ℃ for 24 h, the shear test was performed with a universal testing machine. Stereomicroscope evaluated fracture modes. Stereomicroscope evaluated fracture modes. Data were analyzed by SPSS26.0 statistical software; the standard was P = 0.05. (1) The SEM showed the surface of A1-A4 became rough compared with C. (2) The shear test showed that the highest bonding strength for B was 13.15 ± 2.97 MPa, followed by SB was 7.78 ± 0.97 MPa, and A2 was 7.13 ± 0.75 MPa. However, there was no significant difference between SB and A2 (P > 0.05). Fracture modes of C were the interface fracture of Y-TZP and resin adhesive; most of A1-A4 and SB also were interface fracture, a few mixed fractures, and cohesion fracture of resin adhesive; B were all mixed fracture. Er:YAG laser with 10 Hz could be used as an alternative to sandblasting with Al2O3 for surface modification of Y-TZP to increase the bonding strength.

C-X-C-Chemokine-Receptor-Type-4 Inhibitor AMD3100 Attenuates Pulmonary Inflammation and Fibrosis in Silicotic Mice.

Background: Silicosis is a severe pulmonary disease caused by inhaling dust containing crystalline silica. The progression of silicosis to pulmonary fibrosis is usually unavoidable. Recent studies have revealed positivity for the overexpression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary fibrosis and shown that the CXCR4 inhibitor AMD3100 attenuated pulmonary fibrosis after bleomycin challenge and paraquat exposure. However, it is unclear whether AMD3100 reduces crystalline silica-induced pulmonary fibrosis. Methods: C57BL/6 male mice were instilled intranasally with a single dose of crystalline silica (12 mg/60 µL) to establish an acute silicosis mouse model. Twelve hours later, the mice were injected intraperitoneally with 5 mg/kg AMD3100 or control solution. Then, the mice were weighed daily and sacrificed on day 7, 14, or 28 to collect lung tissue and peripheral blood. Western blotting was also applied to determine the level of CXCR4, while different histological techniques were used to assess pulmonary inflammation and fibrosis. In addition, the level of B cells in peripheral blood was measured by flow cytometry. Results: CXCR4 and its ligand CXCL12 were upregulated in the lung tissues of crystalline silica-exposed mice. Blocking CXCR4 with AMD3100 suppressed the upregulation of CXCR4/CXCL12, reduced the severity of lung injury, and prevented weight loss. It also inhibited neutrophil infiltration at inflammatory sites and neutrophil extracellular trap formation, as well as reduced B-lymphocyte aggregates in the lung. Additionally, it decreased the recruitment of circulating fibrocytes (CD45+collagen I+CXCR4+) to the lung and the deposition of collagen I and α-smooth muscle actin in lung tissue. AMD3100 also increased the level of B cells in peripheral blood, preventing circulating B cells from migrating to the injured lungs. Conclusion: Blocking CXCR4 with AMD3100 delays pulmonary inflammation and fibrosis in a silicosis mouse model, suggesting the potential of AMD3100 as a drug for treating silicosis.

Two New Phenolic Glycosides with Lactone Structural Units from Leaves of Ardisia crenata Sims with Antibacterial and Anti-Inflammatory Activities.

Two new lactones, named Ardisicreolides A-B (1-2), together with four known flavonoids, Quercetin (3), Myricetrin (4), Quercitrin (5), Tamarixetin 3-O-rhamnoside (6), were isolated from the ethyl acetate portion of 70% ethanol extracts of dried leaves from Ardisia crenata Sims. These compounds were identified from Ardisia crenata Sims for the first time. The structures of 1-6 were elucidated according to 1D and 2D-NMR methods and together with the published literature. All of the isolated compounds were evaluated for in vitro anti-microbial effect against Escherichia coli, Pseudomonas aeuroginosa, Enterococcus faecalis, Proteus vulgaris, Staphylococcus aureus, and Bacillus subtilis. In addition, compounds 1-2 were assessed for anti-inflammatory activity by acting on LPS-induced RAW 264.7 macrophage cells in vitro. The results showed that only compound 2 exhibited moderate antibacterial activity on Bacillus subtilis. Moreover, compounds 1 and 2 were found to significantly inhibit the production of nitric oxide (NO) and reduce the release of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-4 (IL-4), and interleukin-10 (IL-10) in LPS-induced RAW 264.7 macrophage cells. The present data suggest that lactones from the leaves of A. crenata Sims might be used as a potential source of natural anti-inflammatory agents.

Investigation of a haze-to-dust and dust swing process at a coastal city in northern China part I: Chemical composition and contributions of anthropogenic and natural sources.

The long retention of dust air masses in polluted areas, especially in winter, may efficiently change the physicochemical properties of aerosols, causing additional health and ecological effects. A large-scale haze-to-dust weather event occurred in the North China Plain (NCP) region during the autumn-to-winter transition period in 2018, affecting the coastal city Qingdao several times between Nov. 27th and Dec. 1st. To study the evolution of the pollution process, we analyzed the chemical characteristics of PM2.5 and PM10-2.5 and source apportionments of PM2.5 and PM10, The dust stagnated around NCP and moved out and back to the site, noted as dust swing process, promoting SO42- formation in PM2.5 and NO3- formation in PM10-2.5. Source apportionments were analyzed using the Positive Matrix Factorization (PMF) receptor model and weighted potential source contribution function (WPSCF). Before the dust invasion, Qingdao was influenced by severe haze; waste incineration and coal burning were the major contributors (~80 %) to PM2.5, and the source region was in the southwest of Shandong Province. During the initial dust event, mineral dust and the mixed factor of dust and sea salt were the major contributors (46.0 % of PM2.5 and 86.5 % of PM10). During the polluted dust period, the contributions of regional transported biomass burning (22.3 %), vehicle emissions (20.8 %), and secondary aerosols (33.8 %) to PM2.5 from the Beijing-Tianjin-Hebei region significantly increased. The secondary aerosols source was more regional than that of vehicle emissions and biomass burning and contributed considerably to PM10 (30.8 %) during the dust swing process. Our findings demonstrate that environmental managers should consider the possible adverse effects of winter dust on regional and local pollution.

Glycogen metabolism reprogramming promotes inflammation in coal dust-exposed lung.

Long-term coal dust exposure triggers complex inflammatory processes in the coal workers' pneumoconiosis (CWP) lungs. The progress of the inflammation is reported to be affected by disordered cell metabolism. However, the changes in the metabolic reprogramming associated with the pulmonary inflammation induced by the coal dust particles are unknown. Herein, we show that coal dust exposure causes glycogen accumulation and the reprogramming of glucose metabolism in the CWP lung. The glycogen accumulation caused by coal dust is mainly due to macrophages, which reprogram glycogen metabolism and trigger an inflammatory response. In addition, 2-deoxy-D-glucose (2-DG) reduced glycogen content in macrophages, which was accompanied by mitigated inflammation and restrained NF-κB activation. Accordingly, we have pinpointed a novel and crucial metabolic pathway that is an essential regulator of the inflammatory phenotype of coal dust-exposed macrophages. These results shed light on new ways to regulate CWP inflammation.

Ratiometric fluorescent sensors for nitrite detection in the environment based on carbon dot/Rhodamine B systems.

A novel carbon dot/Rhodamine B-based ratiometric fluorescent probe was developed for a highly sensitivity and selective detection of nitrite (NO2 -). The probe showed colour changes from blue to orange under ultraviolet light in response to NO2 - with a detection limit as low as 67 nM in the range of 0 to 40 µM. A ratiometric fluorescent test paper was successfully prepared using the probe solution, which demonstrated its feasibility towards a rapid and semi-quantitative detection of NO2 - in real samples.

Vitamin D3 suppresses astrocyte activation and ameliorates coal dust-induced mood disorders in mice.

BACKGROUND: Pneumoconiosis patients exhibit significantly more anxiety and depression than healthy individuals. However, the mechanism of coal dust-induced anxiety and depression remains unclear. METHODS: A pneumoconiosis mouse model with anxiety- and depression-like behaviors were established after 28 days of exposure to coal dust. Vitamin D3 treatment (1200 IU/kg/week) was administered intraperitoneally for 3 months starting from the first coal exposure. Tail suspension test (TST), open field test (OFT), and elevated plus-maze (EPM) test were used to assess anxiety- and depression-like behaviors. Theserum concentration of 25(OH)D3 and fibrillary acid protein (GFAP) expression were determined. In addition, the morphology and distribution of GFAP and neurogenic differentiation factor1 expression (NeuroD1) in different cerebral hippocampus were observed. RESULTS: In coal dust-exposed mice, immobility time decreased in OFT and increased in TST,and the frequency of entering the open arm decreased in the EPM compared with the control mice. Coal dust increased hippocampal GFAP expression and astrocyte activation and reduced neurogenic differentiation factor1 expression (NeuroD1). In addition, Vitamin D3 significantly alleviated anxiety- and depressive-like behaviors in TST and EPM test, decreased GFAP expression level, modified hippocampal astrocyte activation pattern, and advanced brain-derived neurotrophic factor (BDNF) distribution and expression in CA1 and CA3 of the hippocampus. CONCLUSIONS: Taken together, our results suggest that, by inhibiting the over-activation of astrocytes and increasing BDNF and neuron protection, vitamin D treatment ameliorates coal-dust-induced depressive and anxiety-like behavior, which is the first evidence that vitamin D may be a new approach for treating mood disorders caused by particulate matter.

Ratiometric fluorescence sensor for sensitive detection of inorganic phosphate in environmental samples.

Fast, simple, and low-cost on-site visualized detection of inorganic phosphate (Pi) is in great demand since phosphate is the major reason of eutrophication. In this work, a ratiometric fluorescent probe composed by green carbon dots (GCDs) and red carbon dots (RCDs) has been established for high-sensitivity and selective sensing of Pi. A trend of color change from red to green is observed for the detection of Pi under ultraviolet light and the detection limit is 0.09 µM in the range of 0 to 55 µM. Fluorescent test paper prepared from the probe solution was successfully applied to semi-quantitative visual detection of Pi in real-world water and soil samples, which shows great real-world application potentials.

MdSCL8 as a Negative Regulator Participates in ALA-Induced FLS1 to Promote Flavonol Accumulation in Apples.

Apples (Malus domestica) are rich in flavonols, and 5-aminolevulinic acid (ALA) plays an important role in the regulation of plant flavonoid metabolism. To date, the underlying mechanism of ALA promoting flavonol accumulation is unclear. Flavonol synthase (FLS) is a key enzyme in flavonol biosynthesis. In this study, we found that ALA could enhance the promoter activity of MdFLS1 in the 'Fuji' apple and improve its expression. With MdFLS1 as bait, we screened a novel transcription factor MdSCL8 by the Yeast One-Hybrid (Y1H) system from the apple cDNA library which we previously constructed. Using luciferase reporter assay and transient GUS activity assay, we verified that MdSCL8 inhibits the activity of MdFLS1 promoter and hinders MdFLS1 expression, thus reducing flavonol accumulation in apple. ALA significantly inhibited MdSCL8 expression. Therefore, ALA promoted the expression of MdFLS1 and the consequent flavonol accumulation probably by down-regulating MdSCL8. We also found that ALA significantly enhanced the gene expression of MdMYB22 and MdHY5, two positive regulators of MdFLS. We further demonstrated that MdMYB22 interacts with MdHY5, but neither of them interacts with MdSCL8. Taken together, our data suggest MdSCL8 as a novel regulator of MdFLS1 and provide important insights into mechanisms of ALA-induced flavonol accumulation in apples.

Coal dust exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis and Vitamin D remedies.

BACKGROUND: Coal dust particles (CDP), an inevitable by-product of coal mining for the environment, mainly causes coal workers' pneumoconiosis (CWP). Long-term exposure to coal dust leads to a complex alternation of biological processes during regeneration and repair in the healing lung. However, the cellular and complete molecular changes associated with pulmonary homeostasis caused by respiratory coal dust particles remain unclear. METHODS: This study mainly investigated the pulmonary toxicity of respirable-sized CDP in mice using unbiased single-cell RNA sequencing. CDP (< 5 µm) collected from the coal mine was analyzed by Scanning Electron Microscope (SEM) and Mass Spectrometer. In addition, western blotting, Elisa, QPCR was used to detect gene expression at mRNA or protein levels. Pathological analysis including HE staining, Masson staining, immunohistochemistry, and immunofluorescence staining were performed to characterize the structure and functional alternation in the pneumoconiosis mouse and verify the reliability of single-cell sequencing results. RESULTS: SEM image and Mass Spectrometer analysis showed that coal dust particles generated during coal mine production have been crushed and screened with a diameter of less than 5 µm and contained less than 10% silica. Alveolar structure and pulmonary microenvironment were destroyed, inflammatory and death (apoptosis, autophagy, and necrosis) pathways were activated, leading to pneumoconiosis in post 9 months coal dust stimulation. A distinct abnormally increased alveolar type 2 epithelial cell (AT2) were classified with a highly active state but reduced the antimicrobial-related protein expression of LYZ and Chia1 after CDP exposure. Beclin1, LC3B, LAMP2, TGF-ß, and MLPH were up-regulated induced by CDP, promoting autophagy and pulmonary fibrosis. A new subset of macrophages with M2-type polarization double expressed MLPH + /CD206 + was found in mice having pneumoconiosis but markedly decreased after the Vitamin D treatment. Activated MLPH + /CD206 + M2 macrophages secreted TGF-ß1 and are sensitive to Vitamin D treatment. CONCLUSIONS: This is the first study to reconstruct the pathologic progression and transcriptome pattern of coal pneumoconiosis in mice. Coal dust had obvious toxic effects on lung epithelial cells and macrophages and eventually induced pulmonary fibrosis. CDP-induced M2-type macrophages could be inhibited by VD, which may be related to the alleviation of the pulmonary fibrosis process.

Necroptosis in pulmonary macrophages promotes silica-induced inflammation and interstitial fibrosis in mice.

Silicosis is a disease characterized by extensive lung nodules and fibrosis caused by the prolonged inhalation of silica in occupational settings. However, the molecular mechanism of silicosis development is complex and not fully understood. Furthermore, the role of necroptosis, a death receptor-mediated and caspase-independent mode of inflammatory cell death, is not well understood in silicosis. Here, we demonstrate that the necroptotic signaling pathway of macrophages is significantly activated in the lungs of silicosis mouse models. Meanwhile, increased M1 macrophage infiltration and up-regulation of pro-inflammatory cytokines (TNF-α, IL-6) were observed in our silicosis model. Notably, the expression of the pro-fibrotic factor, TGF-ß1, and fibrosis biomarkers α-SMA and collagen I were also unregulated; however, these phenomena were recovered by Nec-1, an inhibitor specific for RIP1 kinase-dependent necroptosis. We conclude that macrophage-mediated necroptosis promotes the progression of silicosis by enhancing lung inflammatory responses and fibrogenesis in a mouse model of silicosis. These findings provide new insights for drug discovery and clinical treatment of silicosis.

RNA-seq-Based Screening in Coal Dust-Treated Cells Identified PHLDB2 as a Novel Lung Cancer-Related Molecular Marker.

Lung cancer is one of the most serious leading cancers with high incidence globally. Identifying molecular markers is key for disease diagnosis and treatment. Coal dust might be important triggering factors in disease development. Here, we first performed RNA-seq-based screening in coal dust treated and nontreated RAW264.7 cell lines. PHLDB2 was found to be the top differentially expressed gene. By retrieving TCGA lung cancer dataset, we observed that PHLDB2 showed upregulations in males and smoker patients. Patients with lower PHLDB2 expression survived longer than those with higher expressions. Furthermore, PHLDB2 was negatively correlated with EMT makers, and a total of 2.74% mutation rate were observed in 1,059 patients. This finding highlights the critical role of PHLDB2 in lung cancer development. PHLDB2 might be a molecular maker for disease diagnosis or treatment.

Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice.

Accumulating evidence reveal that maternal smoking or perinatal nicotine replacement therapy impairs hippocampal neurogenesis, neural development, and cognitive behaviors in the offspring. Microglia is a source of non-neural regulation of neuronal development and postnatal neurogenesis. In this study, we explored the impact of nicotine on the microglia during the development of hippocampus. Developmental nicotine exposure in a mouse model was conducted by supplementing nicotine in the drinking water to mother mice during gestation and lactation period. We found that juvenile offspring with maternal nicotine exposure presented physical and neurobehavioral development delay and an increase in anxiety-like behavior in the open field test on postnatal day (PND) 20. To further detect possible developmental neurotoxic effects of nicotine in offspring and underlying mechanism, whole genome microarray analysis of the expression profile of the hippocampus was performed on postnatal day 20. Significant alterations in the expression of genes related to inflammatory, neurotransmitter, and synapsis were observed in the hippocampus after maternal nicotine exposure, as compared to the vehicle control. Concurrently, an increase in microglial markers and the presence of M2 polarity state in the hippocampus of the nicotine offspring were observed by histological analysis and confocal z-stacking scanning. The M2 microglial polarization state was further confirmed with in vitro primary microglia culture by cytokine array, and double-positive expression of BDNF/Iba1 in microglia by immunohistochemical staining in the juvenile offspring hippocampus was visualized. We also found that nicotine offspring showed an increase of neurite length in the molecular layer and CA1 by Tuj1 staining, as well as an increase in the expression of synapse associated protein, PSD95, but the expression of NeuroD1 in CA1 and CA3 reduced. In summary, maternal nicotine exposure dysregulates immune-related genes expression by skewing the polarity of M2 microglia in the hippocampus, which may cause abnormal cognitive and behavioral performance in the offspring.

Transcriptomic Profiling of Apple Calli With a Focus on the Key Genes for ALA-Induced Anthocyanin Accumulation.

The red color is an attractive trait of fruit and determines its market acceptance. 5-Aminolevulinic acid (ALA), an eco-friendly plant growth regulator, has played a universal role in plant secondary metabolism regulation, particularly in flavonoid biosynthesis. It has been widely reported that ALA can up-regulate expression levels of several structural genes related to flavonoid metabolism and anthocyanin accumulation. However, the molecular mechanisms behind ALA-induced expression of these genes are complicated and still far from being completely understood. In this study, transcriptome analysis identified the differentially expressed genes (DEGs) associated with ALA-induced anthocyanin accumulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the flavonoid biosynthesis (ko00941) pathway was significantly enhanced in the ALA-treated apple calli at 24, 48, and 72 h after the treatment. Expression pattern revealed that ALA up-regulated the expression of the structural genes related to not only anthocyanin biosynthesis (MdCHS, MdCHI, MdF3'H, MdDFR, MdANS, and MdUFGT) but also anthocyanin transport (MdGST and MdMATE). Two R2R3-MYB transcription factors (MdMYB10 and MdMYB9), which are the known positive regulators of anthocyanin biosynthesis, were significantly induced by ALA. Gene overexpression and RNA interference assays demonstrated that MdMYB10 and MdMYB9 were involved in ALA-induced anthocyanin biosynthesis. Moreover, MdMYB10 and MdMYB9 might positively regulate the transcription of MdMATE8 by binding to the promoter region. These results indicate that MdMYB10 and MdMYB9 modulated structural gene expression of anthocyanin biosynthesis and transport in response to ALA-mediated apple calli coloration at the transcript level. We herein provide new details regarding transcriptional regulation of ALA-induced color development.

TLR2 Arg753Gln Gene Polymorphism Associated with Tuberculosis Susceptibility: An Updated Meta-Analysis.

OBJECTIVE: To date, a series of studies were conducted to investigate the association between TLR2 (Toll-like receptor 2) Arg753Gln gene polymorphism and tuberculosis (TB). However, the results were inconsistent. This meta-analysis was performed to elucidate the roles of TLR2 Arg753Gln gene polymorphism in TB. METHODS: All available articles were searched from online databases such as PubMed, Medline, CNKI, and Wanfang. Statistical analyses were performed using the STATA12.0 (Stata Corp LP, College Station, TX, United States) software. RESULTS: 32 case-control studies comprising 5943 cases and 5991 controls were identified in this meta-analysis. Overall, the TLR2 Arg753Gln gene polymorphism was associated with high TB risk in allele model (A vs. G: OR=2.20, 95%CI=1.60-3.04, P≤0.01), dominant model (AA+AG vs. GG: OR=2.70, 95%CI=2.00-3.65, P≤0.01), and heterozygote model (AG vs. GG contrast: OR=2.97, 95%CI=2.39-3.69, P≤0.01). Subgroup analysis by ethnicity indicated that the A allele increased susceptibility to TB in Asian (OR=3.35, 95%CI=2.36-4.74) and Caucasian populations (OR=2.62, 95%CI=1.77-3.87), but not in African (2.08, 95%CI=0.62-2.72) or mixed populations (OR=0.76, 95%CI=0.36-1.14). Stratified analysis by sample type suggested that the A allele associated with high pulmonary tuberculosis (PTB) risks (OR=2.43, 95%CI=1.66-3.54), but not with extra pulmonary tuberculosis (EPTB) (OR=1.84, 95%CI=0.83-4.06). CONCLUSION: this meta-analysis suggested the following: (1) TLR2 Arg753Gln polymorphism is significantly associated with high TB risk. (2) In subgroup analysis based on ethnicity, TLR2 Arg753Gln polymorphism elevates the risk of TB in Asian and Caucasian populations, but not in African or mixed populations. (3) Stratified by sample type, TLR2 Arg753Gln polymorphism is associated with increased PTB risk, but not with EPTB.