High Levels Of NO Research Articles

S-Nitrosylation in endothelial cells contributes to tumor cell adhesion and extravasation during breast cancer metastasis

BackgroundNitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown.ResultsWe report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases.ConclusionsS-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis.

Nitrogen dioxide spatiotemporal variations in the complex urban environment of Athens, Greece

In this study, five years of total, tropospheric and near-surface nitrogen dioxide, ΝΟ2, observations from a Pandora spectrometer system routinely operating in the city center of Athens, Greece, are presented and compared with space-borne observations from the S5P/TROPOMI sensor and in-situ air quality monitoring station measurements from the Greek National Air Pollution Monitoring Network. Each of the three different systems exhibits its own monitoring capabilities and restrictions, based on the spatial representativeness and temporal resolution of its measurements. However, they all reveal a clear weekly pattern with low NO2 concentrations on Sundays while a diurnal cycle with higher levels of NO2 in the morning is observed from the ground due to the high NOx emissions from heavy traffic in the urban environment. A seasonal pattern is further demonstrated by both space- and ground-based remote sensing instruments with enhanced NO2 loadings in wintertime and decreased levels in summertime. Even though, as expected, S5P/TROPOMI appears to underestimate the tropospheric NO2 load, the correlation between the ground-based and space-borne data is relatively high, with corresponding correlation coefficients ranging between 0.73 in spring and 0.80 in winter. High correlations are also found between the relatively new near-surface NO2 product of Pandora and the in situ observations, ranging from 0.91 to 0.99. However, an underestimation is observed by the Pandora instrument compared to those in situ monitoring stations which are highly affected by the increased NOx emissions in the city center. For the Pandora near-surface NO2 at 0° (north) azimuthal viewing angle, the best agreement is found with the urban background in situ stations, with a negative bias at 0.99 ± 1.60 × 1011 molecules cm−3, whereas the Pandora retrievals at 39° (north-east) are closer to the urban in situ NO2 levels, with a bias of −1.10 ± 2.02 × 1011 molecules cm−3 on average.

A marked interannual variability of haze linked to particulate sources and meteorological conditions in Tehran (Iran), 1990–2020

This research assessed the spatio-temporal changes of haze pollution (NHAZEs) and its relationship with levels of gaseous pollutants and meteorological conditions over Tehran metropolis (Iran) for 1990–2020. The results showed a significant decreasing trend of NHAZEs annually and in winter, along with a significant increasing trend in the horizontal visibility. However, a marked interannual variability linked to changes in PM2.5 concentrations and the influence of meteorological conditions was detected, which explained 65% and 30% of the NHAZEs variances, respectively. We found that the increasing trend of wind speed annually and in winter is the principal driver behind the decrease in NHAZEs and the increase in visibility; as winds control the movement and dispersion of air pollution. In relation to gaseous pollutants, a case study showed that the highest concentrations of PM2.5 and NHAZEs were recorded under high levels of SO2, CO, and NO2, and low levels of O3, which mainly occurred under stable anticyclonic circulations. Spatially, the NHAZEs mostly affected the western, southwestern, central, and some parts of the northern of Tehran metropolis, because of the location of industries, traffic, and lack of green areas.

Pitaya (Hylocereus lemairei) extracts avoid mitochondrial dysfunction and NF-kβ/NLRP-3-mediated inflammation in endothelial cells under high glucose and are in vivo safe

BackgroundPitaya has gained popularity as a dietary alternative for diabetics. However, the precise molecular basis and biochemical effects are not well understood. This study aimed to evaluate pitaya influence in endothelial cells under high glucose, mimicking hyperglycemia. MethodsEA.hy926 cells were treated with 1 µg/mL of extract for 24 h with 35 mM of glucose (HG) and/or metformin (MET; 0.5 mM). It was analyzed cell viability/proliferation, apoptosis, ΔΨm, and pHi. Markers of aerobic (NADH and succinate dehydrogenase, and ATP synthase) and anaerobic (LDH) glycolysis were evaluated, as well as NO levels, NF-kβ, and NLRP3 expressions. To determine in vivo safety, acute toxicity in A. salina was conducted (0.5–65 mg/mL). Chemical characterization was performed by HPLC. ResultsHG negatively impacted cell viability and proliferation. Cells presented high levels of extracellular LDH and NO, as well as an increment on NADH, and succinate dehydrogenase activities, and ATP production. Cytometry revealed an increase in ROS levels, apoptosis, and changes in pHi and ΔΨm, accompanied by an increase in NF-kβ, and NLRP3 expressions. These alterations were partially (extract per se pulp and/or associated with MET) or totally (extract per se peel and/or MET associated) reversed. No toxicity for peel extract at concentrations until 65 mg/mL was found. HPLC revealed quercetin and kaempferol in both extracts. ConclusionData indicate that pitaya peel extract is safe and, according to a Principal Component Analysis, can be used as a co-therapeutic strategy to minimize oxidative damage and inflammation in endothelial cells under high glucose.

The joint association of ambient air pollution and different sleep posture with mild obstructive sleep apnea: A study conducted at Taipei Sleep Center

BackgroundGrowing evidence suggests the detrimental impact of supine position and air pollution on obstructive sleep apnea (OSA), as well as the potential benefits of nonsupine positions. However, their interaction effects on OSA remain unclear. ObjectivesTo evaluate the interaction effects of air pollution (NO2/PM2.5) and sleep position on OSA on additive and multiplicative scales. MethodsThis study included 3330 individuals. Personal exposure to air pollution was assessed using a spatiotemporal model. OSA was diagnosed through polysomnography. The associations of supine and nonsupine positions and air pollutants with mild-OSA and their interaction effects on mild-OSA.were explored through generalized logistic regression. ResultsSupine position and high NO2 level independently increased the risk of mild-OSA, while PM2.5 was not associated with mild-OSA. Significant interactions were observed between supine position and NO2 at different lag periods (0–7 days, 0–1 year, and 0–2 years) (P = 0.042, 0.013, and 0.010, respectively). The relative excess risks due to interactions on the additive scale for 1-week, 1-year, and 2-year NO2 exposure and supine position were 0.63 (95 % CI: 0.10–1.16), 0.56 (95 % CI: 0.13–0.99), and 0.64 (95 % CI: 0.18–1.10); the corresponding odds ratios for interactions on the multiplicative scale were 1.45 (95 % CI: 1.01–2.07), 1.55 (95 % CI: 1.09–2.22), and 1.60 (95 % CI: 1.12–2.28). The positive interactions persisted in men and participants with obesity. No interaction was observed between nonsupine position and NO2 levels; nevertheless, significant interactions were noted on both the negative additive and multiplicative scales in men. ConclusionProlonged supine sleep significantly increased the risk of mild-OSA, particularly in men and individuals with obesity. Although the benefits of nonsupine position are considerably less than the risks of NO2 exposure, avoiding prolonged supine sleep may reduce the risk of mild-OSA caused by high levels of NO2 in men.

Integrative assessment of urban dust polycyclic aromatic hydrocarbons using ground and satellite data in Iran.

Recently, for quick urbanization and industrialization, pollutants, especially urban dust, have posed many threats to the human environment. Polycyclic aromatic hydrocarbons (PAHs) are regarded as the main dangerous pollutants that are widespread, persistent, and carcinogenic. The present work aimed to investigate the contamination and sources of PAHs, as well as to assess the risk of cancer for 16 priority PAHs, in urban dust samples in Ahvaz, Isfahan, and Shiraz cities in Iran. We measured PAH concentrations by gas chromatography-mass spectrometry (GC-MS). The average concentrations of the 16 PAHs in Ahvaz, Isfahan, and Shiraz were 6215.11, 7611.03, and 7810.37 μg kg-1, respectively. The domination of low-molecular-weight (LMW) PAHs was observed in Ahvaz, while maximum contribution was observed for high-molecular-weight (HMW) PAHs in Esfahan and Shiraz. For PAHs' source identification, diagnostic ratio, correlation analysis, clustering, and positive matrix factorization (PMF) model were used. PAHs had a combustion (coal and wood, oil, fossil fuels) and gasoline/diesel engine emissions in all cities. Comparative studies suggest that the PAH compounds' level is higher in the research area than in other countries, except for China and India. Also, the pollution of urban dust PAHs has increased over time compared to previous studies in the same cities. The cancer risk from exposure to dust contaminated with PAHs was assessed using the Incremental Lifetime Cancer Risk (ILCR) model. According to the findings, a high risk of exposure to cancer was observed in Ahvaz, Isfahan, and Shiraz. However, compared to adults, children are at higher risk of cancer in their daily lives via dermal contact and unconscious ingestion. Based on the ILCR values, the risk of cancer is in the order of Shiraz > Isfahan > Ahvaz. To assess air pollutants and their effects on urban dust, TROPOMI onboard the Sentinel-5P data were used in the studied cities during 2018-2021. The results show that Ahvaz has different high levels of CO compared to the other 2 cities. Also, Isfahan has different high levels of NO2 compared to the other 2 cities, but Shiraz has different low levels of O3. According to satellite time series data, the trend of the Aerosol Absorbing Index (AAI) has been increasing, while there was a decreasing trend in AAI from the beginning of the COVID-19 pandemic until 12 months later. Therefore, the natural and anthropogenic sources of urban dust PAHs have been increasing in all studied cities. Our findings show that PAH compounds in urban dust pose a significant threat to human health. Therefore, strategic management and planning are vital in reducing urban dust pollution.

The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.

Decidual macrophages derived NO downregulates PD-L1 in trophoblasts leading to decreased Treg cells in recurrent miscarriage.

Placental trophoblasts contribute to regulatory T (Treg) function via the programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway during normal pregnancy. Decreased expression of PD-L1 in trophoblasts was closely associated with Treg deficiency in the development of pregnancy failure. Thus, targeting PD-L1 might be a novel therapy to prevent pregnancy loss. However, the mechanisms for modulating the expression of PD-L1 in trophoblasts are an enigma. The proportion of decidual Treg cells, and the profile of decidual macrophages (DMs) sampled from women with normal pregnancy (NP) and recurrent miscarriage (RM) were evaluated by flow cytometry. The expression of Yin and Yang 1 protein (YY1) and PD-L1 in human villous were measured by Immunohistochemistry (IHC), qRT-PCR and western blot. The determination of soluble PD-L1 (sPD-L1) in serum from NP and RM, and trophoblast conditioned media (TCM) was performed by the PD-L1 SimpleStep ELISA kit. Knockdown of YY1 was processed in the human trophoblast derived cell lines, HTR-8 and Bewo, with siYY1 transfection. Peripheral naïve CD4+ T cells were isolated from women with NP for the in vitro culture. The percentages of Treg cells differentiated from peripheral naïve CD4+ T cells were measured by flow cytometry. The interaction between YY1 and CD274 was proved by CHIP. The expression of inducible nitric oxide synthase (iNOS) in decidua was evaluated by IHC. The level of NO in serum from women with NP and RM was determined by the Griess reagent system. The effects of NO on YY1 were determined by the in vitro culture of HTR-8 cells with the NO donor, SNAP. The in vivo model comprising twelve pregnant mice and underwent different treatment. The percentages of Treg cells in murine uterus were measured by flow cytometry. Similarly, Western blot and IHC were performed to determine the expression of YY1 and PD-L1 in murine placenta. Decreased expression of YY1 and PD-L1 in trophoblasts and lower proportion of decidual Treg cells were observed in patients with RM. Knockdown of YY1 contributes to a lower expression of YY1 and PD-L1. Soluble PD-L1 in the supernatant from HTR-8 cells was also decreased with siYY1 administration. Lower Treg differentiation was observed in the presence of supernatant from HTR-8 cells treated with siYY1. CHIP analysis revealed that endogenous YY1 directly occupied the promoter region of the CD274 (PD-L1) gene. Accompanied with increased M1 DMs, higher NO was observed in serum sampled from patients with RM. In the presence of Reduced expression of YY1 and PD-L1 was observed in HTR-8 cells with the treatment of SNAP. Furthermore, less Treg differentiation was observed with SNAP treated TCM. Moreover, our in vivo data found that YY1 deficiency was associated with decreased PD-L1, which further resulting in less Treg differentiation and Treg deficiency at the maternal-fetal interface and increased embryo loss. Our work found the modulatory capacity of YY1 on PD-L1 in trophoblasts during early pregnancy. Furthermore, reduced YY1 was supposed resulting from higher levels of NO produced from the M1 DMs in RM.

Evaluating the effects of columnar NO2on the accuracy of aerosol optical properties retrievals

Abstract. We aim to evaluate the NO2 absorption effect in aerosol columnar properties, namely the aerosol optical depth (AOD), Ångström exponent (AE), and single scattering albedo (SSA), derived from sun–sky radiometers in addition to the possible retrieval algorithm improvements by using more accurate characterization of NO2 optical depth from co-located or satellite-based real-time measurements. For this purpose, we employ multiannual (2017–2022) records of AOD, AE, and SSA collected by sun photometers at an urban and a suburban site in the Rome area (Italy) in the framework of both the Aerosol Robotic Network (AERONET) and SKYNET networks. The uncertainties introduced in the aerosol retrievals by the NO2 absorption are investigated using high-frequency observations of total NO2 derived from co-located Pandora spectroradiometer systems in addition to spaceborne NO2 products from the Tropospheric Monitoring Instrument (TROPOMI). For both AERONET and SKYNET, the standard network products were found to systematically overestimate AOD and AE. The average AOD bias found for Rome is relatively low for AERONET (∼ 0.002 at 440 nm and ∼ 0.003 at 380 nm) compared to the retrieval uncertainties but quite a bit higher for SKYNET (∼ 0.007). On average, an AE bias of ∼ 0.02 and ∼ 0.05 was estimated for AERONET and SKYNET, respectively. In general, the correction seems to be low for areas with low columnar NO2 concentrations, but it is still useful for low AODs (< 0.3), where the majority of observations are found, especially under high NO2 pollution events. For the cases of relatively high NO2 levels (> 0.7 DU), the mean AOD bias was found within the range 0.009–0.012 for AERONET, depending on wavelength and location, and about 0.018 for SKYNET. The analysis does not reveal any significant impact of the NO2 correction on the derived aerosol temporal trends for the very limited data sets used in this study. However, the effect is expected to become more evident for trends derived from larger data sets and in the case of an important NO2 trend. In addition, the comparisons of the NO2-modified ground-based AOD data with satellite retrievals from the Deep Blue (DB) algorithm of the NASA Moderate Resolution Imaging Spectroradiometer (MODIS) resulted in a slight improvement in the agreement of about 0.003 and 0.006 for AERONET and SKYNET, respectively. Finally, the uncertainty in assumptions on NO2 seems to have a non-negligible impact on the retrieved values of SSA at 440 nm leading to an average positive bias of about 0.02 (2 %) in both locations for high NO2 loadings (> 0.7 DU).

Experimental Research on Performance Development of Direct Injection Hydrogen Internal Combustion Engine with High Injection Pressure

<div>As a carbon-free power with excellent performance, the direct injection (DI) hydrogen-fueled internal combustion engine (H<sub>2</sub>-ICE) has the potential to contribute to carbon dioxide (CO<sub>2</sub>)-neutral on-road transport solutions. Aiming at high thermal efficiency, the influences of key factors on thermal efficiency over wide operating conditions of a turbocharging DI H<sub>2</sub>-ICE were investigated under the lean-burn strategy. And the nitrogen oxides (NO<sub>x</sub>) emission characteristics region was clarified in the high efficiency. The results confirm the optimal ignition strategy with the CA50 of 8–9 crank angle degrees after top dead center (°CA ATDC). The late-injection strategy manifests a significant advantage in brake thermal efficiency (BTE) compared with the early-injection strategy, and this advantage can be amplified by the increased load or injection pressure. The effects of injection (EOIs) pressure on BTE exhibit different laws at different EOIs. Under the early-injection strategy, the lower injection pressure improves BTE due to a more sufficient mixing. While under the late-injection strategy with strong mixture stratification, the high injection pressure conditions exhibit a higher BTE due to reduced compression work. In terms of air-fuel ratio, the BTE is improved monotonically with increased λ at low and medium loads. But there is an optimal λ value limited by the oxygen concentration at a high load. The late-injection strategies with high BTE perform a high level of NO<sub>x</sub> emissions, which confirms the strong trade-off relationship between the thermal efficiency and NO<sub>x</sub> emissions of H<sub>2</sub>-ICEs. A moderate late-injection strategy with an EOI of about 40°CA BTDC can significantly reduce the NO<sub>x</sub> emissions with a slight loss in BTE. The injection pressure shows different effects on NO<sub>x</sub> emissions in different EOI ranges, depending on the mixture distribution. In addition, ultra-lean burn and lower intake temperature are effective means to reduce NO<sub>x</sub> emissions without losing thermal efficiency.</div>

Betula pendula trees infected by birch idaeovirus and cherry leaf roll virus: Impacts of urbanisation and NO2 levels

Viruses are frequently a microbial biocontaminant of healthy plants. The occurrence of the infection can be also due to environmental stress, like urbanisation, air pollution and increased air temperature, especially under the ongoing climate change. The aim of the present study was to investigate the hypothesis that worsened air quality and fewer green areas may favour the higher frequency of common viral infections, particularly in a common tree in temperate and continental climates, Betula pendula ROTH.We examined 18 trees, during the years 2015–2017, the same always for each year, in the region of Augsburg, Germany. By specific PCR, the frequency of two viruses, Cherry leaf roll virus (CLRV, genus Nepovirus, family Secoviridae), which is frequent in birch trees, and a novel virus tentatively named birch idaeovirus (BIV), which has been only recently described, were determined in pollen samples. The occurrence of the viruses was examined against the variables of urban index, air pollution (O3 and NO2), air temperature, and tree morphometrics (trunk perimeter, tree height, crown height and diameter). Generalized Non-linear models (binomial logit with backward stepwise removal of independent variables) were employed.During the study period, both CLRV and BIV were distributed widely throughout the investigated birch individuals. CLRV seemed to be rather cosmopolitan and was present independent of any abiotic factor. BIV's occurrence was mostly determined by higher values of the urban index and of NO2. Urban birch trees, located next to high-traffic roads with higher NO2 levels, are more likely to be infected by BIV.Increased environmental stress may lead to more plant viral infections. Here we suggest that this is particularly true for urban spaces, near high-traffic roads, where plants may be more stressed, and we recommend taking mitigation measures for controlling negative human interventions.

Cloning, DNA sequence, and expression of flagellins from high and low virulence strains of Edwardsiella tarda and their macrophage-stimulating activities.

Edwardsiella tarda is a causative pathogen of edwardsiellosis in fish. Our previous studies on high (NUF251) and low (NUF194) virulent strains of E. tarda demonstrated that NUF251 strain induced significantly higher levels of NO and TNF-α from fish and mouse macrophages than NUF194 strain. Subsequent studies suggested that a flagellin-like protein secreted from E. tarda might be a responsible factor for the macrophage-stimulating activities. To evaluate the activities of flagellins of E. tarda, in this study, the flagellin genes of NUF251 and NUF194 strains were isolated by PCR and cloned into pQE-30 and pCold I expression vectors, and then the recombinant flagellins of two strains were overexpressed in E. coli JM109 and pG-Tf/BL21, respectively. The molecular weight of the purified recombinant flagellins of NUF251 and NUF194 strains were estimated to be 45kDa and 37kDa, respectively on SDS-PAGE analysis. Referring the three-dimensional structure of Salmonella flagellin, which has been reported to have 4 domains (D0, D1, D2, and D3), high sequence homology between two flagellins of E. tarda was observed at conservative domain (D0 and D1) regions, whereas the sequences equivalent to D2 and D3 domains were different, and even equivalent to 57 amino acids were deleted in NUF194. Both recombinant flagellins induced NO production, mRNA expression level of inducible NO synthase (iNOS), and intercellular ROS production in mouse macrophage cell line RAW264.7cells. Also, the secretion of TNF-α and its mRNA expression level were increased by treatment of both recombinant flagellins. These results indicate that the recombinant flagellins from different virulent E. tarda strains can stimulate macrophages with nearly equal levels as judged by the parameters tested, even though they are differences in the structure and molecular weight, suggesting that conservative D0 and D1 domains are sufficient structural elements for the recombinant flagellins to induce a certain level of macrophage-stimulation in vitro. Further studies are necessary focusing on the role of D2 and D3 domain regions of the recombinant flagellins as macrophage-stimulating agent as well as their influence on host immune system in vivo.

Exploring nitric oxide as a crucial prognostic biomarker of coronary artery disease

PurposeThe study aimed to examine if the polymorphism of the endothelial nitric oxide synthase (eNOS) gene variable number of tandem repeats (VNTR) and the serum NO levels are associated with CAD. Materials/methodsCase-control study, 70 CAD and 30 control subjects were enrolled. The eNOS gene polymorphism was measured by polymerase chain reaction–agarose gel electrophoresis and the serum NO was assessed by using an ELISA plate and reader covering 540 nm. ResultsUncovering the area under curve (AUC) for serum NO, which was (0.6821), indicating that NO seemed to be a critical prognostic biomarker of CAD; also, glucose, serum creatinine and total bilirubin proved to be significant predictors of CAD with AUC (0.6793, 0.6717 and 0.6662) respectively. Furthermore, higher serum NO levels were associated with the eNOS (ab) genotype. Revealing the intron (a) allele was protective against CAD. Moreover, diminished levels of serum NO in CAD groups compared to controls (P < 0.05). Additionally, Multiple logistic regression analysis shows a significantly high Odds ratio associated with CAD in the Duhok population. ConclusionsThe eNOS (ab) variant seems to be a protective CAD factor for patients. Low serum NO levels are another risk factor for the advancement of CAD, suggesting their involvement in atherosclerosis. The (a) allele's protective effect is mediated through changes in eNOS promoter activity and higher NO levels.

Design, synthesis and evaluation of nitric oxide releasing derivatives of 2,4-diaminopyrimidine as novel FAK inhibitors for intervention of metastatic triple-negative breast cancer

To search for novel medicines for intervention of triple-negative breast cancer (TNBC), a series of phenylsulfonyl furoxan-based 2,4-diaminopyrimidine derivatives (8a-t) were designed and synthesized based on blocking FAK-mediated signaling pathways through both kinase-dependent and -independent manners. The most active compound 8f not only significantly inhibited FAK kinase activity (IC50 = 27.44 nM), displayed potent inhibitory effects on the proliferation (IC50 = 0.126 μM), invasion and migration of MDA-MB-231 cells, superior to the most widely studied FAK inhibitor, TAE226, bearing 2,4-diaminopyrimidine, but also released high levels of NO, contributing to blockage of FAK mediated-signaling pathways by upregulating of p53 as well as suppressing the Y397 phosphorylation and its downstream effectors, including p-Akt, MMP-2, and MMP-9 via kinase-independent manner, leading to apoptosis induction and decrease of FAs and SFs in TNBC cells. Importantly, 8f inhibited the lung metastasis of TNBC in vivo. Together, 8f may serve as a promising candidate for the treatment of metastatic TNBC.

Assessing neuropsychological disorders affecting pottery workers occupationally exposed to air pollutants

ObjectivePottery-related activities are characterized by the emission of multiple air pollutants in the form of particulate matter, gases, and organic compounds. These pollutants are associated with adverse neuropsychological effects. This study aimed at investigating the effect of occupational exposure to air pollutants on the neuropsychiatric health. MethodsA total of 180 male workers (90 exposed workers and 90 administrative employees) were recruited from pottery-making activities in the Fawakher region located in old Cairo (Misr Al-Kadema); the administrative employees were the control group. Personal, medical, and family histories, general and neurological clinical examination, and neuropsychological assessments were recorded. Serum levels of 4-hydroxy-2-nonenal levels (4HNE) were measured by ELISA. Environmental measurement of workplace air pollutants was performed. ResultsEnvironmental monitoring of the workplace revealed that workers are exposed to high levels of SO2 and NO2 as these exceeded the national standard levels. Compared to the control group, the exposed workers’ group demonstrated a significant decrease in digit forwards score, digit backward score, and symbol digit score and a significant higher Hamilton Depression Scale score, and Benton Visual Retention score. The level of 4HNE was significantly increased among the exposed workers’ group compared to that of the control group. ConclusionOccupational exposure to air pollutants is associated with impairment in neuropsychological functions, with a corresponding increase in the serum level of 4HNE, which is a biomarker for oxidative stress among Egyptian pottery workers.

The risk of hidden “hot spots” with high levels of air pollution in Madrid (Spain)

All urban areas at risk of breathing polluted air should be identified. In the outskirts of Madrid (Spain), there are roads with high traffic (highway A5) that are &lt;5 meters away from nearby residential homes and schools with children and adolescents. The objective of this study is to ascertain the levels of NO2 in these populated areas. Several NO2 diffusion tubes were installed at a height of 3-m to measure NO2 concentrations in various locations of the A5 during the month of May 2022 (30 days). The four tubes located near the A5 measured a NO2 concentration of 49.7; 88.2; 56.8; and 60 μg/m³. The standard deviation and variation coefficient of the measurements were 0.5 and 2.7%, respectively. According to the WHO (2021), the admissible average annual limit is 10 μg/m³ and the daily limit is 25 μg/m³. This study aimed at measuring the concentration of NO2 near homes and primary and secondary schools located in a “toxic microenvironment” (close to the A5 in Madrid) found high and dangerous levels of NO2 impacting the health of the population. This is an area with a population of low socioeconomic level, which increases the impact on health.

Evaluation of diagnostic accuracy of NS1 antigen and oxidative stress for Dengue virus infection in Bangladeshi population

The dramatic rise of global incidence of dengue infection has generated an urgent yet an unmet need for an accurate and validated diagnostic test for DENV infection. A total of 81 serum samples were enlisted to dengue NS1 ICT test and dengue NS1 ELISA test and oxidative stress markers including NO, MDA and SOD activity were measured. Out of 81 samples, 41 were found positive by ELISA (DENV group; n=41) whereas 28 were found positive by ICT test. Out of 81 samples; 40 were found negative (control group; n=40) by ELISA whereas 53 were found negative by ICT test. There were 28 samples which were found positive by both ICT and ELISA test. There were 40 samples which were found negative by both ICT and ELISA. The sensitivity and specificity of ICT test were 68.29% and 100% when compared with ELISA. The positive cases of dengue was confirmed by platelet count having significantly higher level of platelet counts (P&lt;0.0001) in dengue patients compared to that of control. Dengue patients had significantly higher levels of NO (P=0.0007), MDA (P&lt;0.0001) and SOD activity (P&lt;0.0001) compared to those of control. Among dengue patients; a positive correlation was found between MDA level and hematocrit percentage (R2 = 0.8107; P&lt;0.001) and between MDA level and NO level (R2 = 0.4954; P&lt;0.001). The study has unveiled that though the rapid ICT test is cost-effective and with satisfactory specificity, the sensitivity is not up to the mark and possibility of misdiagnosis by this rapid test kit is significant.

Water Quality and Plankton Population Abundance Affected by Earthen Ponds Management

The study was conducted in two earthen ponds fish farming systems located at (El-Rayed area- Kafer El-Shiak governmentEgypt); namely, feed and fertilizer fish farming systems. Each system was replicated in four ponds (8000m2 each), to determine water quality, phytoplankton and zooplankton abundance. Nile tilapia (Orechromis niloticus); mullet (Mugil cephalus) and catfish (Clarias garipinus) were cultured in each pond at initial weight of 2, 30 and 50 g, respectively. The present study aimed to evaluate two fish farming systems differing in pond management procedures in the Nile Delta regions. Results apparent insignificant differences between the two fish farming systems in terms of water temperature (ranged 12.7 to 30.9°C from winter to summer months), salinity, EC and total hardness. Whilst, fertilizer fish farm had significantly high levels of pH, DO, secchi disc, total alkalinity, orthophosphate, TAN, NO2, NO3, algal abundance and chlorophyll “a” n water compared to those of feed fish farm. Significant increase (P&lt;0.05) in phytoplankton and zooplankton abundance were observed in fertilizer fish farm compared to feed fish farm, this was due the high organic manure inputs to pond water during all seasons including winter at one ton per feddan every 10 days.

AIRO: Development of an Intelligent IoT-based Air Quality Monitoring Solution for Urban Areas

Air pollution is the contamination of the atmosphere by any biological, physical, or chemical means. Bengaluru, the Silicon Valley of India, has air pollution levels that exceed WHO standards. Its air has high PM10, PM2.5, SO2, NO2, and CO2 levels, exposing residents to an increased risk of respiratory diseases. AIRO, a decentralised IoT-based air quality monitoring solution, is proposed to calculate the (Air Quality Index) AQI in real-time and notify the users of dangerous AQI levels. Unlike the city's fixed air quality monitoring stations, this portable system can easily be integrated into everyday items for computing real-time air quality at any given place. The proposed solution is then validated using a physical prototype incorporated into a water bottle. Using the Intel Edison development platform, this prototype is equipped with a GPS module, Wi-Fi module, PMS5003, MQ131, MQ135, MQ136, MQ7 sensors, and an LCD Display. The prototype records the air quality indicators, calculates the AQI, and sends the data to the AWS Cloud Server. After an in-depth analysis of the cloud data, the daily and weekly AQI is predicted for multiple locations in the city. A hybrid CNN-Bi-LSTM model is proposed for predicting AQI, which needs to be evaluated at the city scale for dependable results. Finally, a smartphone app is developed using Android Studio and Python to monitor the air quality and notify the users. The users also have an option to select a location and get the real-time and predicted AQI. In the future, this hybrid deep-learning model can be extended to other cities using the transfer learning approach.

Association and interaction of O3 and NO2 with emergency room visits for respiratory diseases in Beijing, China: a time-series study

BackgroundOzone (O3) and nitrogen dioxide (NO2) are the two main gaseous pollutants in the atmosphere that act as oxidants. Their short-term effects and interaction on emergency room visits (ERVs) for respiratory diseases remain unclear.MethodsWe conducted a time-series study based on 144,326 ERVs for respiratory diseases of Peking University Third Hospital from 2014 to 2019 in Beijing, China. Generalized additive models with quasi-Poisson regression were performed to analyze the association of O3, NO2 and their composite indicators (Ox and Oxwt) with ERVs for respiratory diseases. An interaction model was further performed to evaluate the interaction between O3 and NO2.ResultsExposure to O3, NO2, Ox and Oxwt was positively associated with ERVs for total respiratory diseases and acute upper respiratory infection (AURI). For instance, a 10 μg/m3 increase in O3 and NO2 were associated with 0.93% (95%CI: 0.05%, 1.81%) and 5.87% (95%CI: 3.92%, 7.85%) increase in AURI at lag0-5 days, respectively. Significant linear exposure–response relationships were observed in Ox and Oxwt over the entire concentration range. In stratification analysis, stronger associations were observed in the group aged < 18 years for both O3 and NO2, in the warm season for O3, but in the cold season for NO2. In interaction analysis, the effect of O3 on total respiratory emergency room visits and AURI visits was the strongest at high levels (> 75% quantile) of NO2 in the < 18 years group.ConclusionsShort-term exposure to O3 and NO2 was positively associated with ERVs for respiratory diseases, particularly in younger people (< 18 years). This study for the first time demonstrated the synergistic effect of O3 and NO2 on respiratory ERVs, and Ox and Oxwt may be potential proxies.