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.

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.

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.

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.

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.

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.

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.

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.

Prevalence of attention-deficit/hyperactivity disorder symptoms and their associations with sleep schedules and sleep-related problems among preschoolers in mainland China.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) among children is an increasing public health concern. The identification of behavioral risk factors, including sleep quality, has important public health implications for prioritizing behavioral intervention strategies for ADHD. Herein, this study aimed to investigate the prevalence of high levels of ADHD symptoms and to explore the association between sleep schedules, sleep-related problems and ADHD symptoms among preschoolers aged 3 to 6 years in mainland China. METHODS: A cross-sectional study was conducted, comprising a large sample of 15,291 preschoolers in Ma'anshan city of Anhui Province in China. ADHD symptoms were assessed by the 10-item Chinese version of the Conners Abbreviated Symptom Questionnaire (C-ASQ). Sleep-related variables included caregivers' responses to specific questions addressing children's daytime and nighttime sleep schedules, as well as sleep-related behaviors. Data on other factors were also collected, such as socio-demographic characteristics, TV viewing duration on weekdays and weekends, and outdoor activities. Logistic regression models were used to analyze the relationships between sleep schedules, sleep-related problems and ADHD symptoms. RESULTS: Approximately 8.6% of the total sample of preschoolers had high levels of ADHD symptoms, with boys having higher levels than girls (9.9% vs. 7.2%). In the logistic regression analysis, after adjusting for TV viewing duration, outdoor activities, and socio-demographic characteristics, delayed bedtime was significantly associated with a risk of high levels of ADHD symptoms, with odds ratios (OR) of 2.50 [95% confidence interval (CI): 2.09 ~ 3.00] and 2.04 (95% CI: 1.72 ~ 2.42) for weekdays and weekends, respectively. Longer time falling asleep (≥ 31 min) (OR = 1.76, 95% CI: 1.47 ~ 2.11), no naps (OR = 1.57, 95% CI: 1.34 ~ 1.84) and frequent sleep-related problems (OR = 4.57, 95% CI: 3.86 ~ 5.41) were also significantly associated with an increased risk of high levels of ADHD symptoms, while longer sleep duration (> 8.5 h) was associated with a decreased risk of high levels of ADHD symptoms (OR = 0.76, 95% CI: 0.67~ 0.87). CONCLUSIONS: ADHD symptoms are prevalent in preschoolers in Ma'anshan region, China. Undesirable sleep schedules and sleep-related problems among preschoolers confer a risk of ADHD symptoms, highlighting the finding that beneficial and regular sleep habits potentially attenuate ADHD symptoms among preschoolers.

[Correlation of dietary patterns and cognitive function among preschool children in Ma'anshan City in 2014-2015].

OBJECTIVE: To classify the dietary patterns in preschoolers and explore the correlation between dietary patterns and executive functions. METHODS: Between April 2014 and June 2015, 12363 preschoolers were selected from 91 kindergartens of Ma 'anshan City. The classification of dietary patterns and executive functions by Brief-P were evaluated. Unconditional binary logistics regression model was used to analyze the effects of different dietary patterns and executive functions in preschool chidlren. RESULTS: The higher the parents' education level, the lower the executive functions scores, the difference was statistically significant in preschoolers( P < 0. 05). The less intake of "processed model", "drinks model"and "snacks model", the more "vegetarian model"and "health model"intake, executive functions score was lower, and the difference was statistically significant( P < 0. 05). Logistic regression analysis showed that dietary patterns of"processed model"( OR = 1. 44, 95% CI 1. 20-1. 72), "drinks model"( OR = 1. 22, 95% CI 1. 03-1. 46) and "snacks model"( OR = 1. 28, 95% CI 1. 08-1. 52) were risk factors of cognitive functions, and the dietary patterns of "vegetarian model"( OR = 0. 80, 95% CI 0. 67-0. 95) and "health model "( OR = 0. 84, 95% CI 0. 71-0. 98) were protective factors. CONCLUSION: The present study suggests that cognitive functions might be closely related with dietary pattern. The more "vegetarian model"and "health model"intake, the better cognitive functions developed in preschool children.

[Pregnancy-related anxiety and subthreshold autism trait in preschool children based a birth cohort study].

OBJECTIVE: To analyze the associations between pregnancy-related anxiety and the prevalence of subthreshold autism trait (SAT) in preschool children. METHODS: Baseline data came from the Ma'anshan Birth Cohort Study, a part of the China-Anhui Birth Cohort Study (C-ABCS). All the participants were enrolled among pregnant women who received prenatal health care in 4 municipal medical centers during Oct. 2008 to Oct. 2010. A total of 5 084 pregnant women were recruited at the beginning and 4 669 singleton live births were included until childbirth. The situation about pregnancy-specific anxiety during trimester and third trimester of women were evaluated by Pregnancy-specific Anxiety Questionnaire (PAQ). Between April 2014 and April 2015, the cohort was followed up again, and the Clancy Autism Behavior Scale (CABRS) filled out by parents was used for telling the SAT children from the healthy children among 3 663 preschool children. Univariate and binary regression model was used to estimate associations between the pregnancy-related anxiety during trimester and third trimester and the subthreshold autism trait in children. RESULTS: During the pregnancy, the detected rates of women with pregnancy-specific anxiety in trimester and the third trimester were 25.5%(935/3 663), 13.9%(501/3 592) respectively, and the detected rate of maternal pregnancy-specific anxiety in both periods was 7.7%(278/3 592). There were 290 positive children with SAT and the detection rate was 7.9%. After controlling possible confounding factors including children's genders, place of residence, supplement folic acid during pregnancy, preterm birth, exposure to second-hand smoke during pregnancy, the father (mother) cultural levels, the father (mother) nature of work and family income, the results of multinomial logistic regression analysis showed that maternal pregnancy-specific anxiety in trimester was the risk factor for SAT in preschool children (OR=1.51, 95% CI: 1.11-2.04), and there was no association between maternal pregnancy-specific anxiety in the third trimester and SAT in preschool children (OR=1.36, 95% CI: 0.82-2.22). Compared with the single function of maternal pregnancy-specific anxiety in trimester or the third trimester for SAT in preschool children, maternal pregnancy-specific anxiety in both periods presented a joint action that increasing the risk for SAT (OR=2.02, 95% CI: 1.36-2.98). CONCLUSION: Maternal pregnancy-related anxiety was a risk factor for subthreshold autism trait in preschooler children. Pregnant women should try to keep a good mental state to create a good environment for fetal growth.

[Maternal pre-pregnancy body mass index and gestational weight gain with preschool children's overweight and obesity].

OBJECTIVE: To examine the effect of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with childhood overweight and adiposity, and to explore possible early life risk factors for obesity in preschool children. METHODS: Basic information of pregnant women and gestation period came from the Ma'anshan Birth Cohort Study, a part of the China-Anhui Birth Cohort Study (C-ABCS). Pregnant women in routine health care from four municipal medical and health institutions were enrolled voluntarily during October 2008 and October 2010 in Ma'anshan City. A total of 5 084 pregnant women and 4 669 singleton live births were included in this study. Between April 2014 and April 2015, 3 797 children were followed up. Children whose BMI were >85th percentiles for age and genders of World Health Organization (WHO) reference were considered as overweight, and >95th percentiles for age and genders cut-off values were considered as obesity (pathological and secondary causes of obesity were excluded). Gestational weight gain was defined according to the Institute of Medicine (IOM) guidelines. Univariate and binary regression model analysis was used to examine the effect of pre-pregnancy BMI and GWG with childhood overweight and adiposity. RESULTS: Of the 3 797 pregnant women, the prevalence of underweight, normal weight, overweight and obesity were respectively 22.6% (n=858), 70.3% (n=2 671), 6.2% (n=234) and 0.9% (n=34). There were 3 563 pregnant women who were obtained gestational weight gain data, the prevalence of inadequate GWG, appropriate GWG, excessive GWG were respectively 12.4% (n=443), 25.9% (n=922) and 61.7% (n=2 198). The prevalence of overweight and obesity were 11.5% (n=437) and 10.8% (n= 411) in preschool children, respectively. After adjusting confounding factors including age at delivery, genders of children, children age, birth weight, breastfeeding and household economic status, binary logistic regression analysis showed that pre-pregnancy overweight and obesity(OR=2.01, 95% CI: 1.53-2.65), excessive GWG(OR=1.65, 95% CI: 1.35-2.03) were risk factors for overweight and obesity, and pre-pregnancy underweight was protective factor for childhood overweight and obesity (OR=0.49, 95% CI: 0.39-0.62). Joint associations of pre-pregnancy BMI and inappropriate GWG were also noticed in the study: compared to only pre-pregnancy higher BMI or excessive GWG or indequate GWG, combination of high pre-pregnancy BMI and excessive GWG or high pre-pregnancy BMI and inadequate GWG, adverse effects on childhood overweight and obesity were much higher,OR (95%CI) values were 2.90(1.97-4.28), 3.17(1.44-6.97) respectively. CONCLUSION: Both high pre-pregnancy BMI and inappropriate GWG are associated with greater offspring BMI. Pregnant women should achieve appropriate weight gain and help prevent obesity in their children.

[The relationship between maternal emotional symptoms during pregnancy and emotional and behavioral problems in preschool children: a birth cohort study].

OBJECTIVE: To investigate the related influencing factors of preschool children's emotional and behavioral problems in early life and explore the associations between the symptoms of depression or anxiety during pregnancy and emotional and behavioral problems in preschool children. METHODS: Based on the Ma'anshan Birth Cohort Study of the China-Anhui Birth Cohort Study (C-ABCS), women were recruited at their first clinical visit between October 2008 and October 2010 in four municipal medical and health institutions of Ma'anshan City, a total of 5 084 pregnant women and 4 669 singletons live births were included in the birth cohort. Women completed measures of depressive (Self-Rating Anxiety scale) and anxious (Center for Epidemiologic Studies Depression) symptoms in pregnancy. By the age of 3-6 follow-up, 3 653 children were followed with completed information between April 2014 and April 2015, strengths and difficulties questionnaires were used to assessed offspring emotional and behavioral problems. Logistics regression was used to investigate the relationship between the symptoms of depression or anxiety during pregnancy and emotional and behavioral problems in preschool children. RESULTS: The detected rates of emotional symptoms, conduct problems, hyperactivity and peer problems in preschool children were 6.3% (229/3 653), 7.5% (274/3 653), 7.6% (278/3 653) and 2.8% (103/3 653), while 7.6% (277/3 653) for total difficulties, 10.9%(398/3 653) for prosocial behavior and 27.4%(981/3 557) for impact respectively. Prevalence of anxiety and depression in the first trimester was 2.7%(100/3 653) and 4.7%(171/3 653) respectively, and in the second trimester was 2.0%(66/3 375) and 3.6%(122/3 375) respectively. After we controlled the confoundings of gestation age, place of residence, family income, maternal education, paternal education, premature birth and folic acid supplement before pregnancy, multinomial logistic regression analysis showed that the risk of children's emotional symptoms in maternal anxiety in both first-trimester and second-trimester group was higher than the group of no depression and anxiety symptoms, and OR(95%CI) was 5.90(2.00-17.48). Compared with whose mother no depression in both first-trimester and second-trimester, the risk of children's emotional symptoms in maternal depression in both first-trimester and second-trimester group was higher, and OR(95% CI) was 3.07 (1.30-7.28). And the risk of children's total difficulties of maternal anxiety in second-trimester was 2.27 (95%CI: 1.10-4.71) times of no anxiety in second-trimester. While the risk of children's total difficulties of maternal depression in second-trimester was 2.20 (95%CI: 1.24-3.93) times of no depression in second-trimester. Maternal emotional symptoms were not significant associations with conduct problems, hyperactivity, peer problems and prosocial behaviors (P> 0.05). CONCLUSION: There was a negative impact of maternal anxiety and depression symptoms during pregnancy on emotional and behavioral problems in preschool children. These findings highlight the need for additional clinical and research attention to both maternal depression and anxiety in pregnancy, which may be helpful to reduce the incidence of children's emotional and behavioral problems and act as an important measure in prevention.

[Effect of parents' occupational and life environment exposure during six months before pregnancy on executive function of preschool children].

OBJECTIVE: To examine the effect of parents' occupational and life exposure during six months before pregnancy on executive function of preschool children. METHODS: Pregnant women involved in the study came from the Ma'anshan Birth Cohort Study,a part of the China-Anhui Birth Cohort Study. Between October 2008 and October 2010, pregnant women who accepted pregnancy care in four municipal medical and health institutions in Ma'anshan city were recruited as study objects. A total of 5,084 pregnant women and 4,669 singleton live births entered in this cohort. Between April 2014 and April 2015, a total of 3,803 pre-school children were followed up. Finally, except 32 preschool children did not have EF evaluation result, there were 3,771 children included in this study. By using self-designed " Maternal health handbook", we researched parents' general demographic characteristics, and life and occupational exposure during six months before pregnancy. To research preschool children's executive function, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the association of parents' life and occupational exposure during six months before pregnancy and preschool children's EF. RESULTS: 3,771 preschool children's detected rate of inhibitory self-control index (ISCI), flexibility index (FI), emergent metacognition index (EMI) and global executive composite (GEC) dysplasia were 4.8% (182), 2.3% (88), 16.5% (623) and 8.6% (324) respectively. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.86, 95% CI: 1.36-2.54), whose maternal were exposed to pesticides were the risk of ISCI dysplasia(OR=3.60, 95% CI: 1.45-8.95). During six months before pregnancy, children whose maternal were exposed to pesticides (OR=6.72, 95% CI: 2.50-18.07) and whose father were exposed to occupational lead (OR=2.10, 95% CI: 1.25-3.54) were the risk of FI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.42, 95%CI: 1.18-1.71) and whose father were exposed to occupational lead (OR=1.30, 95%CI: 1.02-1.65) were the risk of EMI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.58, 95% CI: 1.24-2.01) and whose maternal were exposed to pesticides (OR=2.39, 95% CI: 1.02-5.58) were the risk of GEC dysplasia. CONCLUSION: The development of executive function is worse among preschool children whose parents live in noise environment, mother exposed to pesticides, and father exposed to occupational lead during six months before pregnancy.

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.

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.

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.

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.

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.