ABSTRACT
MXene, a class of two-dimensional materials that are emerging as rising stars in the field of materials, are receiving much attention in sensing. Ti3C2TxMXene, the most maturely researched MXene, is widely used in energy, biomedical, laser, and microwave shielding applications and has also been expanded to gas sensing and wearable electronics applications. Compared with Ti3C2Tx, Nb2CTxMXene is more difficult to etch and has higher resistances at room temperature; so, few studies have been reported on their use in the sensing field. Based on the preparation of few-layer Nb2CTxMXene by intercalation, this study thoroughly examined their gas-sensing properties. The successfully prepared few-layer Nb2CTxshowed good selectivity and high sensitivity to triethylamine at room temperature, with response values up to 47.2% for 50 ppm triethylamine and short response/recovery time (22/20 s). This study opens an important path for the design of novel Nb-based MXene sensors for triethylamine gas detection.
ABSTRACT
Pharmaceutically active compounds are an important category of emerging pollutants, and their biological transformation processes in the environment are crucial for understanding and evaluating the migration, transformation, and environmental fate of emerging pollutants. The cytochrome P450 105 enzyme family has been proven to play an important role in the degradation of exogenous environmental pollutants. However, its thermostability and catalytic activity still need to be improved to better adapt to complex environmental conditions. This work elucidates the key mechanisms and important residues of the degradation reaction through multiple computational strategies, establishes a mutation library, and obtains 21 single-point mutation designs. Experimental verification showed that 16 single mutants had enhanced thermostability, with the R89F and L197Y mutants showing the highest increases in thermostability at 135 and 119% relative to the wild-type enzyme, respectively. Additionally, as a result of the higher specific activity of D390Q, it was selected for combination mutagenesis, ultimately resulting in three combination mutants (R89F/L197Y, R89F/D390Q, and R89F/L197Y/D390Q) with enhanced thermostability and catalytic activity. This study provides a modification approach for constructing efficient enzyme variants through semirational design and can contribute to the development of control technologies for emerging pollutants.
Subject(s)
Cytochrome P-450 Enzyme System , Diclofenac , Cytochrome P-450 Enzyme System/metabolism , Diclofenac/chemistry , Diclofenac/metabolism , CatalysisABSTRACT
BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.
Subject(s)
Bone Neoplasms , Nanoparticles , Neoplasms , Osteosarcoma , Child , Humans , Adolescent , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Osteosarcoma/diagnostic imaging , Osteosarcoma/therapy , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapy , Immunotherapy , Cell Line, Tumor , PhototherapyABSTRACT
BACKGROUND: Remnant cholesterol (RC) is an important marker for assessing the risk of metabolic syndrome. However, the correlation between RC and hyperuricemia (HUA) remains unclear. This study aimed to explore the correlation between RC and HUA in American adults. METHODS: A total of 9089 participants from the 2013-2020 National Health and Nutrition Examination Survey were investigated. The correlation between RC and the odds of HUA was evaluated using multivariate logistic regression analysis. The nonlinear correlation was described using fitted smoothed curves. The correlation in subgroups was analyzed based on race, gender, alcohol consumption, age, body mass index, waist circumference, diabetes and moderate physical activities. RESULTS: RC was correlated with uric acid (Spearman's correlation coefficient = 0.208 in males and 0.215 in females; all P < 0.001). Multiple logistic regression analysis indicated a positive correlation between RC and the risk of HUA (odds ratio = 1.022 in males and 1.031 in females; all P < 0.001). Subgroup analysis revealed that the correlation was stronger in females, participants aged < 50 years, and those without diabetes. Furthermore, the generalized smooth curve fitting demonstrated a linear correlation between RC and HUA, without threshold or saturation effects. CONCLUSION: Elevated RC significantly and positively correlated with HUA in American adults. This correlation was stronger among females, participants aged < 50 years, and those without diabetes.
Subject(s)
Cholesterol , Hyperuricemia , Nutrition Surveys , Uric Acid , Humans , Male , Female , Hyperuricemia/blood , Hyperuricemia/epidemiology , Middle Aged , Adult , Cholesterol/blood , Uric Acid/blood , United States/epidemiology , Risk Factors , Logistic Models , Aged , Body Mass Index , Waist Circumference , Odds Ratio , Triglycerides/blood , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiologyABSTRACT
Copper plays a crucial role in the heterogenous dissociation of chlorothiophenols (CTPs) to form chlorothiophenoxy radicals (CTPRs), which is the initial and critical step in the formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs). Here, first-principles calculations were performed to investigate the activity of Cu(111) surface towards the formation of adsorbed 2-CTPR from 2-CTP. The interaction between 2-CTP and Cu(111) surface was explored to find stable adsorption configurations. Besides, the decomposition routes of 2-CTP on the Cu(111) surface were further explored. Moreover, the effects of water on the formation of absorbed 2-CTPR on the Cu(111) surface were examined. Our results demonstrate that the flat adsorption of 2-CTP on the surface with adsorption energy in the range of -33.21â¯kcal/mol to -28.37â¯kcal/mol is more stable than the vertical adsorption with adsorption energy ranging from -23.53â¯kcal/mol to -13.38â¯kcal/mol. The Cu(111) surface catalyzes the conversion of 2-CTP into the adsorbed 2-CTPR with a modest energy barrier of 9.46â¯kcal/mol. Furthermore, water molecules exhibit stronger catalytic activity in this process with a decreased energy barrier of 5.87â¯kcal/mol through "water bridge" and hydrogen bonding. Specifically, the water accepts the hydrogen atom from 2-CTP and donates another hydrogen to the surface via "water bridge". This research provides a molecular-level understanding of the heterogeneous formation of PCTA/DTs by fly ash, suggesting novel approaches for control strategy and legislation of dioxin analogues.
Subject(s)
Coal Ash , Copper , Thiophenes , Density Functional Theory , Hydrogen , WaterABSTRACT
Volatile organic compounds (VOCs) significantly contribute to ozone pollution formation, and many VOCs are known to be harmful to human health. Plastic has become an indispensable material in various industries and daily use scenarios, yet the VOC emissions and associated health risks in the plastic manufacturing industry have received limited attention. In this study, we conducted sampling in three typical plastic manufacturing factories to analyze the emission characteristics of VOCs, ozone formation potential (OFP), and health risks for workers. Isopropanol was detected at relatively high concentrations in all three factories, with concentrations in organized emissions reaching 322.3 µg/m3, 344.8 µg/m3, and 22.6 µg/m3, respectively. Alkanes are the most emitted category of VOCs in plastic factories. However, alkenes and oxygenated volatile organic compounds (OVOCs) exhibit higher OFP. In organized emissions of different types of VOCs in the three factories, alkenes and OVOCs contributed 22.8%, 67%, and 37.8% to the OFP, respectively, highlighting the necessity of controlling them. The hazard index (HI) for all three factories was less than 1, indicating a low non-carcinogenic toxic risk; however, there is still a possibility of non-cancerous health risks in two of the factories, and a potential lifetime cancer risk in all of the three factories. For workers with job tenures exceeding 5 years, there may be potential health risks, hence wearing masks with protective capabilities is necessary. This study provides evidence for reducing VOC emissions and improving management measures to ensure the health protection of workers in the plastic manufacturing industry.
Subject(s)
Air Pollutants , Ozone , Volatile Organic Compounds , Humans , Air Pollutants/analysis , Volatile Organic Compounds/analysis , Environmental Monitoring , Risk Assessment , Manufacturing Industry , Alkenes , ChinaABSTRACT
OBJECTIVE: To investigate the prevalence of hyperuricemia among freshmen enrolled in Beijing Sport University and to explore the influencing factors of hyperuricemia in the college population. METHODS: The study period was from September 2021 to February 2022.3372 freshmen of the class of 2021 from Beijing Sport University in Beijing were selected as the study subjects, and two blood uric acid tests were performed on non-same days to calculate the prevalence of the population and to explore the risk factors of hyperuricemia in the college student population using a case-control method.246 people were selected from the hyperuricemia patients of the population to be included in the case group by convenience sampling, and 211 people were selected from the non-hyperuricemia persons of the population to be included in the control group. They were included in the control group, underwent physical and laboratory examinations, and were retrospectively surveyed with questionnaires that included general information such as age, gender, specialty, place of birth, and diet related to hyperuricemia, awareness of hyperuricemia disease, physical activity level, and sleep. Statistical analysis was performed using chi-square analysis, one-way Logistic regression analysis, and multi-factor logistic regression analysis. RESULTS: The number of patients actually diagnosed with hyperuricemia by two blood uric acid tests on non-same days was 479, with a population prevalence rate of 14.21%. Among them, the number of males in the diseased population was 391(22.39%), and the number of females in the diseased population was 88(5.41%). A total of 457 subjects were enrolled in the case-control study, among them, 246 in the case group(218 males and 28 females, average age 19.74 years), 211 in the control group(177 males and 34 females, average age 19.93 years), and 247 in the case group, 211 in the control group, and 2 groups of subjects were included. A total of 211 subjects, and there was no significant difference between the 2 groups in terms of gender composition and age distribution. One-way logistic regression analysis showed that central obesity(OR=31.52, 95%CI 7.59-130.86), obesity(OR=2.59, 95%CI 1.20-5.58), overweight(OR=1.67, 95%CI 1.08-2.59), frequent consumption of fresh vegetables(OR=0.66, 95%CI 0.43-0.99), and drinking 1500-2000 mL of water per day(OR=0.63, 95%CI 0.41-0.95) were associated with hyperuricemia, and multifactorial Logistic regression analyses were performed to analyze the above factors, and finally central obesity(OR=32.05, 95%CI 7.65-134.20), BMI obesity(OR=3.22, 95%CI 1.44-7.20), and daily water intake of 1500-2000 mL(OR=0.60, 95%CI 0.37-0.95) were included in the model at the level of P=0.05. CONCLUSION: The current high prevalence of hyperuricemia in the college student population, which is more prevalent in male college students. Obesity and central obesity are risk factors for hyperuricemia in young college students, and daily water intake of 1500-2000 mL is a protective factor.
Subject(s)
Hyperuricemia , Students , Uric Acid , Humans , Hyperuricemia/epidemiology , Hyperuricemia/etiology , Male , Risk Factors , Prevalence , Female , Universities , Students/statistics & numerical data , Young Adult , Case-Control Studies , Uric Acid/blood , Surveys and Questionnaires , Beijing/epidemiology , Adult , Retrospective Studies , Adolescent , China/epidemiologyABSTRACT
Aerosol nitrate (NO3-) constitutes a significant component of fine particles in China. Prioritizing the control of volatile organic compounds (VOCs) is a crucial step toward achieving clean air, yet its impact on NO3- pollution remains inadequately understood. Here, we examined the role of VOCs in NO3- formation by combining comprehensive field measurements conducted during the China International Import Expo (CIIE) in Shanghai (from 10 October to 22 November 2018) and multiphase chemical modeling. Despite a decline in primary pollutants during the CIIE, NO3- levels increased compared to pre-CIIE and post-CIIEâNO3- concentrations decreased in the daytime (by -10 and -26%) while increasing in the nighttime (by 8 and 30%). Analysis of the observations and backward trajectory indicates that the diurnal variation in NO3- was mainly attributed to local chemistry rather than meteorological conditions. Decreasing VOCs lowered the daytime NO3- production by reducing the hydroxyl radical level, whereas the greater VOCs reduction at night than that in the daytime increased the nitrate radical level, thereby promoting the nocturnal NO3- production. These results reveal the double-edged role of VOCs in NO3- formation, underscoring the need for transferring large VOC-emitting enterprises from the daytime to the nighttime, which should be considered in formulating corresponding policies.
Subject(s)
Air Pollutants , Ozone , Volatile Organic Compounds , Nitrates/analysis , Volatile Organic Compounds/analysis , Air Pollutants/analysis , China , Environmental Pollution/analysis , Environmental Monitoring , Ozone/analysisABSTRACT
BACKGROUND AND AIM: Severe acute pancreatitis (SAP) in patients progresses rapidly and can cause multiple organ failures associated with high mortality. We aimed to train a machine learning (ML) model and establish a nomogram that could identify SAP, early in the course of acute pancreatitis (AP). METHODS: In this retrospective study, 631 patients with AP were enrolled in the training cohort. For predicting SAP early, five supervised ML models were employed, such as random forest (RF), K-nearest neighbors (KNN), and naive Bayes (NB), which were evaluated by accuracy (ACC) and the areas under the receiver operating characteristic curve (AUC). The nomogram was established, and the predictive ability was assessed by the calibration curve and AUC. They were externally validated by an independent cohort of 109 patients with AP. RESULTS: In the training cohort, the AUC of RF, KNN, and NB models were 0.969, 0.954, and 0.951, respectively, while the AUC of the Bedside Index for Severity in Acute Pancreatitis (BISAP), Ranson and Glasgow scores were only 0.796, 0.847, and 0.837, respectively. In the validation cohort, the RF model also showed the highest AUC, which was 0.961. The AUC for the nomogram was 0.888 and 0.955 in the training and validation cohort, respectively. CONCLUSIONS: Our findings suggested that the RF model exhibited the best predictive performance, and the nomogram provided a visual scoring model for clinical practice. Our models may serve as practical tools for facilitating personalized treatment options and improving clinical outcomes through pre-treatment stratification of patients with AP.
Subject(s)
Pancreatitis , Humans , Retrospective Studies , Nomograms , Severity of Illness Index , Acute Disease , Bayes Theorem , Prognosis , Machine LearningABSTRACT
A quantum mechanics/molecular mechanics (QM/MM) approach is a broadly used tool in computational enzymology. Treating the QM region with a high-level DFT method is one of the important branches. Here, taking leaf-branch compost cutinase-catalyzed polyethylene terephthalate depolymerization as an example, the convergence behavior of energy barriers as well as key structural and charge features with respect to the size of the QM region (up to 1000 atoms) is systematically investigated. BP86/6-31G(d)//CHARMM and M06-2X/6-311G(d,p)//CHARMM level of theories were applied for geometry optimizations and single-point energy calculations, respectively. Six independent enzyme conformations for all the four catalytic steps (steps (i)-(iv)) were considered. Most of the twenty-four cases show that at least 500 QM atoms are needed while only two rare cases show that â¼100 QM atoms are sufficient for convergence when only a single conformation was considered. This explains why most previous studies showed that 500 or more QM atoms are required while a few others showed that â¼100 QM atoms are sufficient for DFT/MM calculations. More importantly, average energy barriers and key structural/charge features from six conformations show an accelerated convergence than that in a single conformation. For instance, to reach energy barrier convergence (within 2.0 kcal mol-1) for step (ii), only â¼100 QM atoms are required if six conformations are considered while 500 or more QM atoms are needed with a single conformation. The convergence is accelerated to be more rapid if hundreds and thousands of conformations were considered, which aligns with previous findings that only several dozens of QM atoms are required for convergence with semi-empirical QM/MM MD simulations.
Subject(s)
Hydrolases , Polyethylene Terephthalates , Humans , Catalysis , Molecular Conformation , Molecular Dynamics Simulation , Quantum TheoryABSTRACT
In this paper, a TM polarization multi-band absorber is achieved in a graphene-Ag asymmetrical grating structure. The proposed absorber can achieve perfect absorption at 1108 nm, 1254 nm, and 1712 nm (the absorption exceeds 98.4% at the three peaks). Results show that the perfect absorption effect originates from the excitation of magnetic polaritons (MPs) in the silver ridge grating; a LC equivalent circuit model is utilized to confirm the finite-difference-time-domain (FDTD) simulation. The influences of the incident angle, polarization angle, and geometrical size on the absorption spectrum are investigated. Moreover, a quadruple band absorber and a quintuple band absorber are also designed by introducing more silver grating ridges in one period. The proposed graphene-Ag asymmetrical structure has some advantages compared with other absorbers such as the ability to be independently tuned and a simple structure. Thus, the proposed structure can be applied in the areas of multiple absorption switches, near-infrared modulators, and sensors.
ABSTRACT
In the marine boundary layer (MBL), chlorine (Cl) and chlorine monoxide (ClO) are powerful oxidants with high concentrations. The gas-liquid interface is also ubiquitous in the MBL as a favorable site for atmospheric reactions. Understanding the role of water in Cl/ClO radical chemistry is essential for predicting their behavior in the atmosphere and developing effective strategies for mitigating their harmful effects. However, the research studies on the system of Cl/ClO radicals on the surface of water droplets are still insufficient. In previous studies, we have found unique results related to the hydroxyl radical at the interface using ab initio molecular dynamics (AIMD). In this work, we have used AIMD to investigate interactions between Cl/ClO radicals and water molecules at the gas-liquid interface. Radical mobility, radial distribution functions, coordination, and population analyses were conducted to investigate the surface preference, bonding pattern, and track Cl/ClO radicals in the water droplets. In addition, density functional theory (DFT) analysis was conducted to compare the results at the gas-liquid interface with those in the gas phase. We found that Cl/ClO radicals tend to remain near the gas-liquid interface in water droplet systems and outside of water clusters in gas phase systems. The ClO radical can form O*-H and Cl-O bonds with water molecules; however, neither the O*-O hemibond nor the Cl-H bond was detected in all systems. Different dominant structures were obtained for ClO in the interface and gas phase. The ClO radical can be bonded to one water molecule from its oxygen side, (H2O)0-Cl-O*-(H2O)1 at the interface, or to two water molecules from the chlorine and oxygen sides, (H2O)1-Cl-O*-(H2O)1 in the gas phase. Meanwhile, the Cl radical can only form a dominant structure like Cl*-(H2O)1 at the gas-liquid interface by making a Cl*-O hemibond. Providing a thorough explanation of the Cl/ClO radical behavior at the gas-liquid interface, this study will improve our understanding of the MBL's oxidizing capacity and pollution causes.
ABSTRACT
BACKGROUND: Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency. RESULTS: Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform. CONCLUSIONS: In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.
Subject(s)
Multifunctional Nanoparticles , Neoplasms , Humans , Hydrogen Peroxide , Antineoplastic Combined Chemotherapy Protocols , Doxorubicin/pharmacology , Glutathione , Neoplasms/drug therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Recently there are increasing interests in accurately evaluating the health effects of heterocyclic PAHs. However, the activation mechanism and possible metabolites of heterocyclic PAHs catalyzed by human CYP1A1 is still elusive to a great extent. Here, leveraged to high level QM/MM calculations, the corresponding activation pathways of a representative heterocyclic PAHs, carbazole, were systematically explored. The first stage is electrophilic addition or hydrogen abstraction from N-H group. Electrophilic addition was evidenced to be more feasible and regioselectivity at C3 and C4 sites were identified. Correlations between energy barriers and key structural/electrostatic parameters reveal that O-Cα distance and Fe-O-Cα angle are the main origin for the catalytic regioselectivity. Electrophilic addition was determined as the rate-determining step and the subsequent possible reactions include epoxidation, NIH shift (the hydrogen migration from the site of hydroxylation to the adjacent carbon) and proton shuttle. The corresponding products are epoxides, ketones and hydroxylated carbazoles, respectively. The main metabolites (hydroxylated carbazoles) are estimated to be more toxic than carbazole. The regioselectivity of carbazole activated by CYP1A1 is different from the environmental processes (gas and aqueous phase). Collectively, these results will inform the in-depth understanding the metabolic processes of heterocyclic PAHs and aid the accurate evaluation of their health effects.
Subject(s)
Hydrocarbons, Aromatic , Polycyclic Aromatic Hydrocarbons , Humans , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 Enzyme System/metabolism , Carbazoles , Polycyclic Aromatic Hydrocarbons/metabolism , Hydrogen , Catalysis , HydroxylationABSTRACT
A systematic study of the movement of PAHs (Polycyclic aromatic hydrocarbons) and their derivatives through air, soil, and water is key to understanding the exchange and transport mechanisms of these pollutants in the environment and for ultimately improving environmental quality. PAHs and their derivatives, such as nitrated PAHs (NPAHs), oxygenated PAHs (OPAHs), brominated PAHs (BrPAHs) and chlorinated PAHs (ClPAHs), were analyzed in air, bulk deposition, soil, and water samples collected from urban, rural, field, and background sites on the eastern coast of China. The goal was to investigate and discuss their spatiotemporal variations, exchange fluxes, and transport potential. The concentrations of PAHs and their derivatives in the air and bulk deposition displayed distinct seasonal patterns, with higher concentrations observed during the winter and spring and lower concentrations during the summer and autumn. NPAHs exhibited the opposite trend. Significant urban-rural gradients were observed for most of the PAHs and their derivatives. According to the air-soil fugacity calculations, 2-3 ring PAHs, BrPAHs, and ClPAHs were found to volatilize from the soil into the air, while 4-7 ring PAHs, OPAHs, and NPAHs deposited from the air into the soil. The air-water fugacity of the PAHs and their derivatives indicated that surface water was an important source for the ambient atmosphere in Qingdao. The characteristic travel distances (CTDs) and persistence (Pov) for atmospheric transport were much lower than that for the water samples, which may be due to the longer half-lives of PAHs and their derivatives in water. NPAHs and ClPAHs with long transport distances and strong persistence in water could lead to a significant impact on marine pollution.
ABSTRACT
OBJECTIVE: Our goal in this work was to investigate the possible role and mechanism of regulated in development and DNA damage response 1 (REDD1) in mediating high glucose (HG)-induced podocyte injury in vitro. MATERIALS AND METHODS: Mouse podocytes were stimulated with HG to establish HG injury model. Protein expression was examined by Western blotting. Cell viability was measured by cell counting kit-8 assay. Cell apoptosis was assessed by annexin V-FITC/propidium iodide and TUNEL apoptotic assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified by commercial kits. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß were measured by ELISA. RESULTS: A marked increase in REDD1 expression was observed in podocytes stimulated with HG. Reduced REDD1 expression strikingly restrained HG-induced increases in apoptosis, oxidative stress, and inflammation response in cultured podocytes. Decreasing REDD1 expression enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HG-exposed podocytes via regulation of the AKT/glycogen synthase kinase-3 beta (GSK-3ß) pathway. Inhibition of AKT or reactivation of GSK-3ß prominently abolished Nrf2 activation induced by decreasing REDD1 expression. Pharmacological repression of Nrf2 markedly reversed the protective effects of decreasing REDD1 expression in HG-injured podocytes. CONCLUSION: Our data demonstrate that decreasing REDD1 expression protects cultured podocytes from HG-induced injuries by potentiating Nrf2 signaling through regulation of the AKT/GSK-3ß pathway. Our work underscores the potential role of REDD1-mediated podocyte injury during the development of diabetic kidney disease.
Subject(s)
Podocytes , Mice , Animals , Podocytes/metabolism , Podocytes/pathology , Proto-Oncogene Proteins c-akt/metabolism , NF-E2-Related Factor 2/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Oxidative Stress , Apoptosis , Glucose/toxicity , Glucose/metabolismABSTRACT
Criegee intermediates (CIs) are important zwitterionic oxidants in the atmosphere, which affect the budget of OH radicals, amines, alcohols, organic/inorganic acids, etc. In this study, quantum chemical calculation and Born-Oppenheimer molecular dynamic (BOMD) simulation were performed to show the reaction mechanisms of C2 CIs with glycolic acid sulfate (GAS) at the gas-phase and gas-liquid interface, respectively. The results indicate that CIs can react with COOH and OSO3H groups of GAS and generate hydroperoxide products. Intramolecular proton transfer reactions occurred in the simulations. Moreover, GAS acts as a proton donor and participates in the hydration of CIs, during which the intramolecular proton transfer also occurs. As GAS widely exists in atmospheric particulate matter, the reaction with GAS is one of the sink pathways of CIs in areas polluted by particulate matter.
Subject(s)
Protons , Sulfates , Particulate Matter , Molecular Dynamics Simulation , AminesABSTRACT
Criegee intermediates (CIs) are important in the sink of many atmospheric substances, including alcohols, organic acids, amines, etc. In this work, the density functional theory (DFT) method was used to calculate the energy barriers for the reactions of CH3CHOO with 2-methyl glyceric acid (MGA) and to evaluate the interaction of the three functional groups of MGA. The results show that the reactions involving the COOH group of MGA are negligibly affected, and that hydrogen bonding can affect the reactions involving α-OH and ß-OH groups. The water molecule has a negative effect on the reactions of the COOH group. It decreases the energy barriers of reactions involving the α-OH and ß-OH groups as a catalyst. The Born-Oppenheimer molecular dynamic (BOMD) was applied to simulate the reactions of CH3CHOO with MGA at the gas-liquid interface. Water molecule plays the role of proton transfer in the reaction. Gas-phase calculations and gas-liquid interface simulations demonstrate that the reaction of CH3CHOO with the COOH group is the main pathway in the atmosphere. The molecular dynamic (MD) simulations suggest that the reaction products can form clusters in the atmosphere to participate in the formation of particles.
Subject(s)
Molecular Dynamics Simulation , Water , Amines , Atmosphere , ProtonsABSTRACT
New particle formation (NPF) contributes more than half of the global aerosol. Diethanolamine (DEA) and methyldiethanolamine (MDEA) are the most common amines used to remove CO2 and H2S, which are lost to the atmosphere from CO2 chemical absorbers, livestock and consumer products and are involved in sulfuric acid (SA)-driven NPF. Ion-induced nucleation (IIN) is an important nucleation pathway for NPF. We investigated the role of IIN on DEA and MDEA enhancing SA-driven NPF using density functional method (DFT), molecular dynamics (MD) simulation and atmospheric cluster dynamics code (ACDC). The effects of SO42-, H3O+, NH4+, HSO4-, NO3-, ammonia, methylamine, dimethylamine, trimethylamine and water (W) on the nucleation of SA-DEA were further investigated. The enhancement ability of DEA is greater than that of dimethylamine (DMA) and MDEA. Participation in SA-based NPF is a removal pathway for DEA and MDEA. DEA-SA clusters are generated that not only aggregate DEA and SA molecules, but also increase further growth of atmospheric ions. The very low Gibbs formation free energy highlights the importance of ion-induced nucleation for SA-based NPF. The order of the ability of common atmospheric ions to increase the (SA)(DEA) cluster nucleation is SO42- > H3O+ > NH4+ > HSO4- > NO3-. The addition of 20 water molecules increases the (SA)(DEA)9 cluster from 1.882 nm to 2.053 nm, promoting SA-based NPF. The atmospheric ions accelerate the aggregation rate of the (SA)5(DEA)5 cluster within 15 ns?
Subject(s)
Amines , Carbon Dioxide , Amines/chemistry , Sulfuric Acids/chemistry , Dimethylamines/chemistry , WaterABSTRACT
Due to non-specific strong nano-bio interactions, it is difficult for nanocarriers with permanent rough surface to cross multiple biological barriers to realize efficient drug delivery. Herein, a camouflaged virus-like-nanocarrier with a transformable rough surface is reported, which is composed by an interior virus-like mesoporous SiO2 nanoparticle with a rough surface (vSiO2 ) and an exterior acid-responsive polymer. Under normal physiological pH condition, the spikes on vSiO2 are hidden by the polymer shell, and the non-specific strong nano-bio interactions are effectively inhibited. While in the acidic tumor microenvironment, the nanocarrier sheds the polymer camouflage to re-expose its rough surface. So, the retention ability and endocytosis efficiency of the nanocarrier are great improved. Owing to it's the dynamically variable rough surface, the rationally designed nanocarrier exhibits extended blood-circulation-time and enhanced tumor accumulation.