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Elevated exposure to multiple trace metals can be neurotoxic even at relatively low levels. These findings are primarily evident from adult occupational studies as well as in children exposed prenatally or in early childhood. Less research has focused on the neurodevelopmental impacts of exposure to metals among school-aged children. We examined associations between exposure to a mixture of four metals (arsenic, cadmium, manganese, lead) measured in hair and markers of cognition, attention, and behavior among 222 6-12 year old children who participated in a 2009-2010 neurodevelopmental follow-up to the C8 Health Project. Using quantile-based g-computation we estimated the adjusted overall metal mixture effect ψ (95 % CI) as the change in outcome per decile increase in all metals in the mixture. Hair metal levels varied by metal, with cadmium being lowest (median 0.007, interquartile range (IQR) 0.013 μg/g) and lead the highest concentration (median 0.152, IQR 0.252 μg/g). Children's cognitive skills and development, attention/impulsivity, and behavior were all close to standardized population means. Each decile increase in all metals was associated with a Full Scale IQ reduction of 1.01 points (95 % confidence interval (CI) -1.88, -0.15) and Verbal IQ reduction of 1.11 points (95 % CI -1.97, -0.25), adjusted for child age, sex, secondhand smoke exposure, HOME score, maternal education, maternal IQ, and examiner. Maternal report of ADHD-like behaviors and executive functioning also showed adverse associations with the metal mixture. Our findings suggest that similar to exposure during prenatal and early childhood periods, recent exposure to metals during middle childhood is associated with adverse neurodevelopmental consequences. Middle childhood may also be a developmental window of susceptibility to the negative consequences of exposure to environmental neurotoxicants.

BackgroundThe molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.ObjectivesTo assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.MethodsOur study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.ResultsWe found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionOur results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.

Periodontitis is one of the most prevalent dental diseases, and the patients with periodontitis often suffer from refractory periodontitis or recurrence of disease due to improper or inadequate treatment. In clinical practice, the early and accurate assessment of post-treatment prognosis in periodontitis patients is always very important in order to implement timely interventions. In this study, a pre-treatment saliva SERS based prognostic protocol was explored to predict the prognosis of periodontal non-surgery therapy in periodontitis patients. According to the biomolecular analysis, significant differences in the levels of ascorbic acid, uric acid and glutathione are observed between good prognosis group and poor prognosis group, which are expected to serve as potential prognostic markers. Furthermore, high accuracy, sensitivity and specificity can also be achieved by using the proposed prognostic model. The excellent performance of the proposed method has demonstrated its potential for fast, accurate, and non-invasive prognostic prediction of periodontal non-surgery therapy in periodontitis patients, even at the time before implementing treatment, thus is expected to benefit timely and rational guidance on clinical interventions.

This study investigated the recovery of K

Summary Background Pregnancy is associated with deteriorations in maternal bone strength and heightened susceptibility to bone fractures. We aimed to investigate whether ambient particulate matter (PM)2·5 concentrations were associated with bone strength during pregnancy. Methods In this longitudinal cohort study, we analysed longitudinal data from women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City, Mexico. Eligible women were aged 18 years or older, at less than 20 weeks' gestation at the time of recruitment, planning to stay in Mexico City for the next 3 years, without heart or kidney disease, did not use steroids or anti-epileptic drugs, were not daily consumers of alcohol, and had access to a telephone. Daily ambient PM2·5 concentrations were estimated from a spatio-temporal model that was based on the individual's address. Trabecular bone strength was measured using quantitative ultrasound from the radius of the middle finger and cortical bone strength from the proximal phalanx of the middle finger, during the second trimester, third trimester, and 1 and 6 months post partum. Bone strength T scores were modelled with PM2·5 concentrations using linear mixed models and distributed lag models. Findings Adjusting for multiple exposure windows, each 10 ug/m3 increase in PM2·5 exposure concentrations in the first trimester was associated with a 0·18 SD decrease (95% CI −0·35 to −0·01; p=0·033) in ultrasound speed-of-sound (SOS) T score of trabecular bone strength from the second trimester until 6 months post partum. Similarly, each 10 μg/m3 increase in third trimester PM2·5 exposure was associated with a 0·18 SD decrease (–0·36 to −0·01; p=0·044) in the SOS T score of trabecular bone strength from the third trimester until 6 months post partum. PM2·5 exposure in the first month post partum was associated with a 0·20 SD decline (–0·39 to −0·01; p=0·043) in cortical bone strength until 6 months post partum. Interpretation Ambient PM2·5 exposure during and after pregnancy was associated with diminished trabecular and cortical bone strength. Early pregnancy PM2·5 exposure was associated with a greater decline in bone strength later during pregnancy. Late pregnancy and early post-partum exposures adversely affected the post-partum bone strength recovery. Technological and policy solutions to reduce PM2·5 pollution could improve public health by reducing bone fracture risk. Funding US National Institute of Environmental Health Sciences.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women. Various mechanisms are involved in the initiation and progression of breast cancer. Metabolic dysregulation has been associated with increasing breast cancer incidence and mortality. However, little is known about how metabolic disease regulates the development and progression of breast cancer at the molecular level. Here, using a hybridization capture-based panel including 124 cancer-associated genes, we performed targeted next-generation sequencing of tumor tissues and matched blood samples from 20 postmenopausal patients with primary breast cancer, in which 6 cases suffered from preexisting metabolic disorders including hypertension, type 2 diabetes, and coronary heart disease. We took only the protein-altering variants and identified 170 somatic mutations of 59 genes. Among these, 40 mutated genes were found in the metabolic disease group, and 33 mutated genes were found in the non–metabolic disease group. Importantly, nonsynonymous mutations of 26 genes (MSH3, BRAF, MLH3, MTOR, DDR2, ALK, etc.) were uniquely present in the metabolic disease group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to investigate biological functions and key pathways of somatic mutations. TP53, PIK3CA, and PTEN were the top three commonly mutated genes at a higher frequency compared with the Cancer Genome Atlas (TCGA) data, and several novel but infrequent mutations in other genes were also found. Although further studies are required to validate these variants, our results are the first to suggest a specific molecular profile of breast cancer with preexisting metabolic disease.

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen which can cause pneumonia, sepsis and infections of skin and soft tissue. The host mostly relies on innate immune responses to defend against the infection of A. baumannii. Currently, it has been confirmed that fibroblasts involved in innate immune responses. Therefore, to explore how bovine skin fibroblasts mediated immune responses to defend against A. baumannii infection, we analyzed the differential transcripts data of bovine skin fibroblasts infected with bovine A. baumannii by RNA-sequencing (RNA-seq). We found that there were 3014 differentially expressed genes (DEGs) at 14h with bovine A. baumannii infection, including 1940 up-regulated genes and 1074 down-regulated genes. Gene Ontology (GO) enrichment showed that ubiquitin protein ligase binding, IL-6 receptor complex, ERK1 and ERK2 cascade terms were mainly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that innate immune pathways were significantly enriched, such as TNF, IL-17, NLR, MAPK, NF-κB, endocytosis, apoptosis and HIF-1 signaling pathways. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that GO terms such as chemokine receptor binding and Th17 cell differentiation and KEGG pathways such as TLR and cytokine-cytokine receptor interaction pathways were up-regulated. In addition, CASP3 and JUN were the core functional genes of apoptosis, while IL-6, ERBB2, EGFR, CHUK and MAPK8 were the core functional genes of immunity by Protein-Protein Interaction (PPI) analysis. Our study provided an in-depth understanding of the molecular mechanisms of fibroblasts against A. baumannii infection. It also lays the foundation for the development of new therapeutic targets for the diseases caused by A. baumannii infection and formulates effective therapeutic strategies for the prevention and control of the diseases caused by A. baumannii.

Particles transported by a fluid flow can accumulate in preferential regions. Usually, the clustering is caused by particle inertia, leading to inertial coherent particle structures. In the absence of inertia, particles can also cluster massively in a steady flow, solely owing to their size when they are repelled from a boundary by lubrication and lift forces. These forces can transfer the particles from the chaotic region to Kolmogorov–Arnold–Moser tori of the unperturbed incompressible flow, where they may focus on three-dimensional limit cycles. Numerical simulations for two different flow systems, taking into account the boundary-repulsion effect for finite-size particles, are in very good agreement with corresponding experiments. The results provide evidence that finite-size coherent particle structures are generic for a class of incompressible flows.

BACKGROUND: Phthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women. OBJECTIVE: To determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery. METHODS: We analyzed 15 urinary phthalate biomarker concentrations during the 2(nd) and 3(rd) trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2(nd) and 3(rd) trimesters), short-term weight (between 3(rd) trimester and 12 months post-delivery), and long-term weight (between 18 months and 6 – 7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers. RESULTS: As a mixture, 2(nd) trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2(nd) and 3(rd) trimesters (interquartile range, IQR, difference: −0.07 standard deviations, SD; 95% credible interval, CrI: −0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2(nd) and 3(rd) trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6–7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP. CONCLUSIONS: Prenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women.

The field of wastewater management has seen a transition from “contaminant removal” in wastewater treatment plants (WWTPs) to “nutrient recovery” in so-called water resource recovery facilities (WRRFs) for years. For achieving a higher efficiency and economic benefits, the integration of multiple nutrient recovery technologies (NRTs) is of increased interest. This study provides a comprehensive overview of the integration of ammonia stripping, adsorption and struvite precipitation, three of the most dominant physicochemical NRTs. In their different combinations, a critical comparison of the available research is given from the perspective of process technical description, the current scale of application and potential challenges and perspectives ahead. The integration between ammonia stripping and struvite precipitation has been applied in either “one single integrated reactor” at lab scale or “multiple discrete reactors” at pilot/full scale. The collection of struvite should be further optimized, and “stripping → K-struvite precipitation” is expected to recover all of three macronutrients. In the technical integration between struvite precipitation and adsorption, small pristine adsorbents (

Lead is a ubiquitous pollutant with deleterious effects on human health and remains a major current public health concern in developing countries. This heavy metal may interfere with nucleic acids via oxidative stress or epigenetic changes that affect biological markers of aging, e.g., telomere length and DNA methylation (DNAm). Telomere shortening associates with biological age in newborns, and DNA methylation at specific CpG sites can be used to calculate "epigenetic clocks".The aim of this study was to examine the associations of prenatal lead exposures with telomere length and DNA-methylation-based predictors of age in cord blood.The study included 507 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a birth cohort in Mexico City. Maternal blood (second trimester, third trimester and at delivery) and bone lead levels (one month postpartum) were measured using inductively coupled plasma-mass spectrometry and X-ray fluorescence, respectively. Cord blood leukocyte telomere length was measured using quantitative PCR and apparent age by DNA methylation biomarkers, i.e., Horvath's DNA methylation age and the Knight's predictor of gestational age.Average maternal age was 28.5 ± 5.5 years, and 51.5% reported low socioeconomic status. Children's mean telomere length was 1.2 ± 1.3 relative units, and mean DNA methylation ages using the Horvath's and Knight's clocks were -2.6 ± 0.1 years and 37.9 ± 1.4 weeks (mean ± SD), respectively. No significant associations were found between maternal blood and bone lead concentrations with telomere length and DNAm age in newborns.We found no associations of prenatal lead exposure with telomere length and DNA methylation age biomarkers.

We introduce an interesting and challenging routing and scheduling problem arising in the city operations of SF Express, a large package express carrier in China. Vehicles execute multiple trips during a planning horizon spanning multiple shifts, where a trip can involve deliveries only, pickups only, or deliveries followed by pickups. Complicating factors include split deliveries and pickups, cross-trip consistency requirements, and limited unloading capacity at the main hubs. We develop an optimization-based multi-phase heuristic solution approach seeking to minimize the number of vehicles used. An extensive computational study using real-world instances demonstrates the effectiveness of the approach.

Background Phthalates, a chemical class of plasticizers, are ubiquitous environmental contaminants that have been associated with oxidative stress. Mitochondria DNA copy number (mtDNAcn) and DNA deletions (mtDNAdel) are emerging biomarkers for cellular oxidative stress and environment exposures. Objectives To examine associations of urinary phthalate metabolite and isoprostane concentrations on sperm mtDNAcn and mtDNAdel in male partners undergoing assisted reproductive technologies (ART). Methods Ninety-nine sperm samples were collected from male partners undergoing ART at Baystate Medical Center in Springfield, MA as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Seventeen urinary phthalate metabolite concentrations were analyzed by the Centers for Disease Control using tandem mass spectrometry. Urinary 15-F2t-isoprostane concentrations, a biomarker of lipid peroxidation, were measured using a competitive enzyme-linked immunosorbent assay. A triplex qPCR method was used to determine the relative quantification of mtDNAcn and mtDNAdel. Results Sperm mtDNAcn and mtDNAdel were positively correlated (Spearman rho = 0.31; p = .002). Adjusting for age, BMI, current smoking, race, and measurement batch, urinary monocarboxy-isononyl phthalate (MCNP) concentrations were positively associated with mtDNAcn (β = 1.63, 95% CI: 0.14, 3.11). Other urinary phthalate metabolite and isoprostane concentrations were not associated with sperm mtDNAcn or mtDNAdel. Conclusions Among this cohort of male ART participants, those with higher MCNP had higher mtDNAcn; other phthalate metabolites and isoprostane were not associated with mtDNAcn and mtDNAdel. Given our relatively small sample size, our results should be interpreted with caution. Future research is needed to replicate the findings in larger studies and among sperm samples obtained from the general population.

Background Pregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy. Objectives To examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health. Design We quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4–5 and 6–8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models. Results As a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: −0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: −0.08 SD, 95%CrI: −0.16, −0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL. Conclusions Phthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed.

Since 1965, polybrominated diphenyl ethers (PBDEs) have been used internationally as flame-retardant additives. PBDEs were recently withdrawn from commerce in North America and Europe due to their environmental persistence, bioaccumulative properties and endocrine-disrupting effects. Generations exposed perinatally to the highest environmental doses of PBDE account for one-fifth of the total United States population. While, toxicity of PBDE for the male reproductive system has been demonstrated in several human and animal studies, the long-lasting effects of perinatal exposures on male reproduction are still poorly understood. In this study, pregnant Wistar rats were exposed to 0.2 mg/kg 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) from gestation day 8 until postnatal day 21. Male reproductive outcomes were analyzed on postnatal day 120 in offspring. Exposed animals had significantly smaller testes, displayed decreased sperm production per testis weight, had significantly increased percentage of morphologically abnormal spermatozoa, and showed an increase in spermatozoa head size. Perinatal BDE-47 exposure led to significant changes in testes transcriptome, including suppression of genes essential for spermatogenesis and activation of immune response genes. In particular, we observed a 4-fold average decrease in expression of protamine and transition protein genes in testes, suggesting that histone-protamine exchange may be dysregulated during spermatogenesis, resulting in an aberrant sperm epigenome. The possibility of long-lasting effects of developmental PBDE exposures calls for additional studies to build a foundation for the development of preventive and protective interventions against the environmentally-induced decline in fertility.

We evaluate the performance of four machine learning methods for modeling and predicting FCC solute diffusion barriers. More than 200 FCC solute diffusion barriers from previous density functional theory (DFT) calculations served as our dataset to train four machine learning methods: linear regression (LR), decision tree (DT), Gaussian kernel ridge regression (GKRR), and artificial neural network (ANN). We separately optimize key physical descriptors favored by each method to model diffusion barriers. We also assess the ability of each method to extrapolate when faced with new hosts with limited known data. GKRR and ANN were found to perform the best, showing 0.15 eV cross-validation errors and predicting impurity diffusion in new hosts to within 0.2 eV when given only 5 data points from the host. We demonstrate the success of a combined DFT + data mining approach towards solving materials science challenges and predict the diffusion barrier of all available impurities across all FCC hosts., Comment: 13 pages, 4 figures

Orbital angular momentum (OAM), an emerging and fascinating degree of freedom, has highlighted an innovation in communication and optical manipulation field. The beams with different OAM state, which manifest as the phase front “twisting” of electromagnetic waves, are mutually orthogonal, which is exactly what a new freedom applied to practical communication eagers for. Herein, we proposed a novel millimeter-wave OAM modulation technique by electrically optical phase controlling. By modulating OAM and phase of optical-millimeter-wave synchronously, the multi-modulation: quadrature orbital angular momentum modulation (QOM) communication system at W band is structured and simulated, allowing a 50 Gbit/s signal transmitting with bit-error rates less than 10−4. Our work might suggest that OAM could be compounded to more complex multi-modulation signal, and revealed a new insight into OAM based high capacity wireless and radio-over-fiber communication.

Network applications require traffic to sequence through multiple types of middleboxes to enhance network functions, e.g., providing security and guaranteeing performance. Sequenced-middlebox policy routing on top of regular layer 2/3 flow routing is challenging to be flexibly managed by network administrators. In addition, various types of middlebox resources concurrently obtained by numerous applications complicate network-resource management. Furthermore, middlebox failures can lead to a lack of security and the malfunction of entire network. In this paper, we formulate a mixed-integer linear programming problem to achieve a network load-balancing objective in the context of sequenced-middlebox policy routing. Our global routing approach manages network resources efficiently by simplifying candidate-path selections, balancing the entire network and using the simulated annealing algorithm. Moreover, in case of middlebox failures, we design a fast recovery mechanism by exploiting the remaining link and middlebox resources locally. To the best of our knowledge, this is the first work to handle failures in sequenced-middlebox scenarios using OpenFlow. Finally, we implement proposed routing approaches on Mininet testbed and evaluate experiments' scalability, assessing the effectiveness of the approaches. Results of the optimization on a test topology include an increase up to 26.4% of the throughput with respect to a sequenced shortest-path routing.

Kinetic degradation of phenacetin (PNT) by solar activated persulfate (PS) system was evaluated in study. The decomposition of PNT well fitted with a pseudo-first order kinetic pattern, and the exceptional removal performance towards PNT (100%) was obtained in the presence of solar irradiation (1.14 × 10-4 E· m−2· s−1) and 0.3 mM PS at pH 7.0 in 10 min. The consume ratios of persulfate were calculated to be 2.3~16.7%. The steady-state concentrations of hydroxyl radicals ([HO*]ss) and sulfate radicals ([SO4-·]ss) were calculated to be (2.41~2.59) × 10-13 M and (3.75~4.06) × 10-12 M by probes of nitrobenzene (NB) and benzoic acid (BA), respectively. The contribution of HO* and SO4-· accounts for 27.4% and 11.0% in degradation of PNT. The formation of typical trihalomethanes (THMs) after pre-oxidation of solar/PS was evaluated. The concentration of total THMs decreased from 16 μg·L-1 to 15.4 μg·L-1 through pre-oxidation, with cytotoxicity decreased from 1.38 × 10-5 to 1.27 × 10-5. The calculated electrical energy per order (EE/O) in solar/PS were in range of 0.069~0.106 kWh/m/order.

Intervertebral disc degeneration (IDD) is the major pathogenesis of lower back pain. Tyrosol is a polyphenolic compound that exhibits anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Herein, we explored the effects and mechanisms of tyrosol on IDD progression in interleukin (IL)-1β-stimulated human nucleus pulposus cells (HNPCs). Cell viability and apoptosis were detected by CCK-8 and flow cytometry analysis, respectively. The production of tumor necrosis factor-α (TNF-α), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was examined to evaluate inflammation. The mRNA expression of matrix metalloproteinases (MMPs) (MMP-3/9/13), collagen type II, SRY-related high mobility group box 9 (SOX-9), and aggrecan was measured by qRT-PCR. Protein levels of silent information regulator 2 homolog 1 (Sirt1), phosphorylated protein kinase B (p-Akt), Akt, collagen type II, SOX-9, and aggrecan were determined by western blot. Results showed that tyrosol attenuated IL-1β-induced viability reduction, apoptosis, and caspase-3/7 activity in HNPCs. The increase in the production of TNF-α, IL-6, NO, and PGE2 in IL-1β-treated HNPCs was abolished by tyrosol treatment. Tyrosol treatment reversed IL-1β-induced upregulation of MMP-3, MMP-9, and MMP-13, and downregulation of collagen II, SOX-9, and aggrecan in HNPCs. Additionally, tyrosol treatment activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in IL-1β-stimulated HNPCs. Sirt1 was upregulated by tyrosol, and Sirt1 silencing inhibited Akt phosphorylation in HNPCs. Sirt1 knockdown attenuated the effects of tyrosol on IL-1β-induced apoptosis, inflammation, and ECM remodeling in HNPCs. In summary, upregulation of Sirt1 by tyrosol suppressed apoptosis and inflammation and regulated ECM remodeling in IL-1β-stimulated HNPCs through activation of PI3K/Akt pathway.

Light-emitting diode (LED) is environmentally friendly with longer life compared with traditionally mercury lamps. This study investigated the non-steroidal anti-inflammatory drugs (NSAIDs)- phenacetin (PNT) and acetaminophen (ACT)- removal during LED-UV (365 nm) photolysis of free available chlorine (FAC). Degradation of PNT and ACT during LED-UV365/FAC treatment at pH 5.5-8.5 followed the pseudo-first order kinetics. The presence of hydroxyl radicals (·OH), reactive chlorine species (RCS), and ozone (O3, transformed from O (3P)) were screened by using scavengers of ethanol (EtOH), tert-Butanol (TBA), and 3-buten-2ol, and 4-hydroxy-2,2,6,6-tetramethylpiperidine (TEMP), and quantified by competition kinetics with probing compounds of nitrobenzene (NB), benzoate acid (BA), 1,4-dimethoxybenzene (DMOB). Higher pH would lead to decrease of ·OH contribution and an increase of FAC contribution to PNT and ACT degradation. It has been determined that the contribution of O3 to degradation of PNT and ACT was less than 5% for all pHs, and O3(P) reacts toward EtOH with second-order constant of 1.52 × 109 M-1s-1. LED-UV365/FAC system reduced the formation of five typical CX3-R type disinfection by-products (DBPs) as well as the cytotoxicity and genotoxicity of water samples at pH 5.5 and 8.5, compared with FAC alone. The decrease of DBPs formation resulted from fast FAC decomposition upon LED-UV365 irradiation. A feasible reaction pathway of DBPs formation in the LED-UV365/FAC system was examined with density functional theory (DFT). For FAC decay during LED-UV365/FAC with effluent from wastewater, the residual FAC in 15 min was 0.8 mg/L (lower than limit of 0.2 mg/L) once initial FAC was 2.0 mg/L. The results indicate that more tests on the balance of target pollutant removal efficiency, residual FAC and cost should be explored in LED-UV365/FAC system for application.

Ninety nine Salmonella isolates recovered from 1414 retail meats were characterized by serotyping, antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE), presence of amino acid mutation in quinolone resistance determination region (QRDR) of DNA gyrase subunit A (GyrA) and topoisomerase IV subunit C (ParC), and of qnrA, qnrB, qnrS, aac(6′)-Ib, qepA, and oqxAB. Among 1414 retail meat samples, 96 (6.8%) including 49 (9.0%) chickens, 22(6.8%) lambs, 10 (4.8%) beefs, 13 (6.8%) porks and 2(1.4%) horse meats were positive to Salmonella. The commonly detected Salmonella serotypes were S. Hadar (n = 21, 21.2%), S. Enteritidis (n = 17, 17.2%), S. London (n = 17, 17.2%), and S. Havana (n = 11, 11.1%). Eighty four (84.8%) isolates were simultaneously resistant to more than three antimicrobial agents. Antibiotic resistance was most commonly found to trimethoprim (100%), and a less extent to chloramphenicol (88.9%), tetracycline (63.6%), nalidixic acid (58.6%), sulfisoxazole (57.6%), streptomycin (43.4%), trimethoprim/tulfisoxazole (41.4%), ampicillin (25.6%), amoxicillin/clavulanate (25.6%), kanamycin (6.1%), ceftriaxone (5.1%), gentamicin (3.0%), cefoxitin (2.0%), and amikacin (1.0%). qnrA (11.1%), qnrB (34.3%), qnrS (8.1%), aac(6′)-Ib (7.1%), qepA (7.1%), oqxA (10.1%) and oqxB (9.1%) were detected from the 99 isolates. Amino acid substitutions of Asp87Asn (4.8%), Asp87Tyr (28.6%), Asp87Val (4.8%), Ser83Phe (52.4%), Ser83Tyr (7.1%) and Gly75Phe (2.4%) in GyrA were detected, as well as Thr57Ser (98.6%) and Gly53Val (1.4%) in ParC. Mutations of Ser83Phe (GyrA)/Thr57Ser (ParC) that simultaneously detected in GyrA and ParC were found in 22 isolates. Totally 82 different DNA patterns generated after the 99 isolates were subtyped using PFGE. The results demonstrated that the prevalence of Salmonella in retail meats in Uighur of Xinjiang province were not common, however, the isolates exhibited multidrug resistance, phenotypical and genotypical diverse.

A smartphone-integrated ratiometric fluorescent sensing system (DPA-Ce-GMP-Eu) for visual and point-of-care testing (POCT) of tetracycline with high sensitivity and accuracy was developed. The blue fluorescence of DPA-Ce-GMP was changed into red by doping with Eu3+ duo to the energy transfer from Ce3+ to Eu3+. Upon exposure to tetracycline, coordination between Eu3+ and tetracycline blocks energy transfer from Ce3+ to Eu3+, converting the fluorescent color from red to blue. The tetracycline detection can be realized within a wide concentration range from 0.01 μM to 45 μM. The limit of detection (LOD) reaches as low as 6.6 nM. To realize quantitative point-of-care detection in real samples, a portable device with smartphone as signal reader and analyzer is further designed to integrate with the DPA-Ce-GMP-Eu sensing platform. The Color Picker APP installed in the smartphone can convert the Red, Green and Blue (RGB) channels of the fluorescence images into digital values. With milk as real sample, tetracycline can be on-site detected with LOD of 10.8 nM. This developed platform presents a great promise for POCT in practical application with merits of low cost, easy carry, simple operation, and excellent selectivity and repeatability.

Interdependent network models are often used to show how one network has an effect on another network through dependencies. In this paper, we propose a novel interdependent network model which consists of two individual networks with unequal numbers of nodes and one-to-multiple weighted dependency links between the two networks. Based on realistic assumptions, this model differs from previous works that considered equal numbers of nodes in the two networks and identical dependency links. We formulate an optimization problem to allocate dependency links using least resources. This novel model enhances the practicability of traditional cyber–physical system structures, but it makes the dependency link deployment problem more complex and the optimization problem cannot be solved in large networks. To overcome this problem, we propose a new algorithm based on a revised network flow method. Extensive simulations on random networks and real networks show that our deployment method produces topologies that are more robust than the ones obtained by other deployment techniques. Results indicate that our algorithm is efficient and cost-effective in designing robust interdependent networks, and our deployment method is suitable for networks of any size.