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1.
Sci Total Environ ; 752: 141784, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889265

RESUMO

Emerging evidence suggests that perinatal dioxin exposure affects neurodevelopment and impairs multiple brain functions, including cognitive, language, learning and emotion, in the offspring. However, the impacts of gestational and lactational exposure to dioxin on behavior and related molecular events are still not fully understood. In this study, female C57BL/6J mice were orally administered three doses of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1 or 10 µg/kg body weight (bw)) during the pregnancy and lactation periods. The locomotion, exploration and anxiety-related behaviors were examined by an open field test of the young adult female offspring at postnatal day 68. We found that the maternal TCDD exposure, particularly at a low dose, increased movement ability, novelty-exploration and certain anxiety-related behaviors in the offspring. Such hyperactivity-like behaviors were accompanied by the upregulation of certain genes associated with cholinergic neurotransmission or synaptogenesis in the offspring brain. In accordance with the potential enhancement of cholinergic neurotransmission due to the gene upregulations, the enzymatic activity of acetylcholinesterase was decreased, which might lead to excess acetylcholine and consequent hyper-excitation at the synapses. Thus, we found that gestational and lactational TCDD exposure at low dose caused hyperactivity-like behaviors in young adult female offspring and speculated the enhancement of cholinergic neurotransmission and synaptogenesis as potential molecular events underlying the neurobehavioral effects.


Assuntos
Dibenzodioxinas Policloradas , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Lactação , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Dibenzodioxinas Policloradas/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
2.
Talanta ; 221: 121464, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076084

RESUMO

A sandwich temperature control membrane inlet system based on a miniature mass spectrometer is presented that demonstrates improved analytical performance for the measurement of dissolved gases and volatile organic compounds (VOCs) in aqueous solution. Aqueous solution is directly brought to the monolayer flat membrane interface at a constant flow rate. A heating resistor and a thermocouple are fixed on the side of the membrane and aqueous solution respectively. This new strategy allows for a temperature compensation method, affording an improvement of sensitivity and a reduction of response time compared with the conventional heating solution temperature control strategy. Furthermore, a static heating mode is applied to effectively remove the memory effect. Automatic sampling and measurement are achieved by using the membrane inlet system with silicone sheeting of 50 µm thickness. The vacuum is below 3 × 10-5 Torr, which can make the instrument work normally. A good linear response is observed for benzene in the range of 0.1 ppm-10 ppm and the detection limit is 50 ppb. The analytical capacity of this system is demonstrated by the on-line analysis of VOCs in aqueous solution, in which the dominant ions are detected rapidly. The results indicate that the sandwich temperature control membrane inlet mass spectrometer (STC-MIMS) has a potential application for on-line analyzing organic pollution in aquatic environments.

3.
Chemosphere ; 262: 127741, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32781330

RESUMO

In recent years, the dramatic increase in antibiotic use has led to the evolution of antibiotic resistant genes (ARGs), posing a potential risk to human and aquatic ecological safety. In this study, source contribution and correlations between twelve antibiotics and their corresponding ARGs were firstly investigated in surface water in the Fuxian Lake. The results showed that sulfamethoxazole (SMX) (0.98-14.32 ng L-1) and ofloxacin (OFL) (0.77-7.3 ng L-1) were the dominant antibiotics in surface water, whereas erythromycin-H2O (EM-H2O), SMX and OFL posed the medium risk to aquatic organisms. Meanwhile, the mean concentrations of MLs in inflowing rivers were 5.6 times more than those in the lake, which was related to dilution and degradation. Moreover, the facter1 (co-sources L (Living quarters), M (Mining area), A (Agricultural district) and T (tourist area)) contributed 78% of antibiotic concentrations, and the source L was predominant. The results also revealed the prevalence of intL1, sul1 and sul2 in all the sampling sites, and that the abundance of ARGs in the lake was significantly lower (P < 0.01) than that in inflowing rives. Additionally, significant correlations (p < 0.0001) between intL1 and sulfanilamide resistance genes (sul1, sul2) were detected, indicating that intL1 promoted the propagation and they originated from the same anthropogenic sources. Overall, our findings revealed the presence of antibiotics and ARGs and their inconsistent correlations in the Fuxian Lake, which provides a foundation to support further exploration of the occurrence and transmission mechanisms of antibiotics and ARGs.

4.
Sci Total Environ ; 751: 141726, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889464

RESUMO

Ultrafine particles (UFPs) are of concern because of their high pulmonary deposition efficiency. However, present control measures are generally targeted at fine particles (PM2.5), with little effect on UFPs. The health effects of UFPs at different PM2.5 concentrations may provide a basic for controlling UFPs but remain unclear in polluted areas. School children spend the majority of their time in the classrooms. This study investigated the different short-term effects of indoor UFPs on school children in Beijing, China when indoor PM2.5 concentrations exceeded or satisfied the recently published Chinese standard for indoor PM2.5. Cardiopulmonary functions of 48 school children, of whom 46 completed, were measured three times. Indoor PM2.5 and UFPs were monitored in classrooms on weekdays. Measurements were separated into two groups according to the abovementioned standard. Mixed-effect models were used to explore the health effects of the air pollutants. Generally, UFP-associated effects on children's cardiopulmonary function persisted even at relatively low PM2.5 concentrations, especially on heart rate variability indices. The risks associated with high PM2.5 concentrations are well-known, but the effects of UFPs on children's cardiopulmonary function deserve more attention even when PM2.5 has been controlled. UFP control and standard setting should therefore be considered.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Pequim , Criança , China , Monitoramento Ambiental , Humanos , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise
5.
Environ Pollut ; 267: 115621, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254614

RESUMO

The emergence of a novel coronavirus named SARS-CoV-2 during December 2019, has caused the global outbreak of coronavirus disease 2019 (COVID-19), which is officially announced to be a pandemic by the World Health Organization (WHO). The increasing burden from this pandemic is seriously affecting everyone's life, and threating the global public health. Understanding the transmission, survival, and evolution of the virus in the environment will assist in the prevention, control, treatment, and eradication of its infection. Herein, we aimed to elucidate the environmental impacts on the transmission and evolution of SARS-CoV-2, based on briefly introducing this respiratory virus. Future research objectives for the prevention and control of these contagious viruses and their related diseases are highlighted from the perspective of environmental science. This review should be of great help to prevent and control the epidemics caused by emerging respiratory coronaviruses (CoVs).

6.
J Exp Clin Cancer Res ; 39(1): 268, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256802

RESUMO

BACKGROUND: Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. METHODS: Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome data in HCC Cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in Cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic features. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic properties on stemness features of HCC cells via interacting with co-cultured non-tumor cells. RESULTS: High levels of glycolysis-related metabolites and genes were present in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes' expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. CONCLUSIONS: In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.

7.
Neural Plast ; 2020: 8885729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144854

RESUMO

Depression and pain disorders share a high degree of comorbidity. Inflammatory mechanisms play an important role in the pathogenesis of depression-chronic somatic pain comorbidity. In this study, we investigated the effects of acupuncture on blood and brain regional tumor necrosis factor alpha (TNF-α) in rats with depression and chronic somatic pain comorbidity. Forty Sprague-Dawley rats were randomly divided into the following 4 groups with 10 each: control, model, model treated with transcutaneous auricular vagus nerve stimulation (taVNS), and model treated with electroacupuncture (EA). Chronic unpredictable mild stress (CUMS) with chronic constriction injury of the sciatic nerve (CCI) was used to produce depression and chronic somatic pain comorbidity in the latter 3 groups. The rats of the taVNS and EA groups received, respectively, taVNS and EA at ST 36 for 28 days. Pain intensity was measured using a mechanical withdrawal threshold and thermal stimulation latency once biweekly. Depressive behavior was examined using a sucrose preference test at baseline and the end of modeling and intervention. The level of plasma TNF-α and the expression of TNF-α in the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus were measured. While CUMS plus CCI produced remarkable depression-like behavior and pain disorders, EA and taVNS significantly improved depression and reduced pain intensity. CUMS plus CCI also resulted in a significant increase in plasma TNF-α level and the expression in all brain regions examined compared to the intact controls. Both EA and taVNS interventions, however, suppressed the elevated level of TNF-α. These results suggest that EA and taVNS have antidepressant and analgesic effects. Such effects may be associated with the suppression of TNF-α-related neuroinflammation.

8.
Ann Palliat Med ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33222467

RESUMO

BACKGROUND: Pain in amyotrophic lateral sclerosis (ALS) has a considerable impact on the quality of life of both patients and their caregivers, and thus the identification and evaluation of pain characteristics in ALS should be addressed. However, due to the scarcity of research data, pain in ALS is still frequently underestimated and insufficiently treated. The aim of this study was to investigate the characteristics of pain in patients with ALS using standardized pain questionnaires. METHODS: Eighty-nine patients diagnosed with ALS were interviewed. Consecutive patients with peripheral neuropathy were used as control subjects and were matched to the ALS subjects by age and sex. Patient data including gender, age, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and the pain severity index (PSI) were collected. The characteristics between ALS and peripheral neuropathy, and between ALS patients with and without pain were compared. RESULTS: In all, 89 patients with ALS and 89 control subjects with peripheral neuropathy were included. There were no significant differences in sex ratio and age between the two groups. There were significantly more patients with pain symptoms in the ALS group (35/89, 39%) than in the peripheral neuropathy group (20/89, 22%). Quality of life was significantly affected in the ALS patients with pain (using ALS patients without pain as control subjects). CONCLUSIONS: The results suggested that pain was a significant symptom in patients with ALS and had a considerable impact on quality of life.

9.
J Clin Neurosci ; 81: 122-132, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33222901

RESUMO

Treatments enhancing angiogenesis for chronic cerebral hypoperfusion (CCH) are still in the research stage. Although encephalomyosynangiosis (EMS) is a common indirect anastomosis for the treatment of CCH, the effectiveness to promote angiogenesis is not satisfactory. Vascular endothelial growth factors (VEGF) is a cytokine found to specifically act directly on vascular endothelial cells, promote neovascularization, and enhance capillary permeability. However, the short half life and unstable property of VEGF underlies the need to explore available delivery system. In this study, poly (lactide-co-glycolide) (PLGA) was used to prepare VEGF controlled-release microspheres. In vitro and in vivo analysis of release kinetics showed that the microspheres could release VEGF continuously within 30 days. Then, modified chronic cerebral hypoperfusion rat model was established by ligation of bilateral internal carotid artery and one vertebral artery. At 14 days after ischemia, the EMS and the VEGF microspheres injection were performed. At 30 days after the injection, the result of Morris water maze displayed that combinating VEGF microspheres and EMS significantly ameliorated cognitive deficit after ischemia. We observed that combinating VEGF microspheres and EMS could further significantly increase cerebral blood flow. We speculated that this enhancement of cerebral blood flow was attributed to more angiogenesis induced by combination of VEGF microspheres and EMS, which verified by more collateral circulation with cerebral angiography and higher expression of CD31 or α-SMA. Our study demonstrated that combinating VEGF-PLGA controlled-release microspheres could significantly promote angiogenesis in EMS-based CCH rats model, providing new ideas for clinical treatment of CCH.

10.
Sci Total Environ ; : 143738, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33223188

RESUMO

The government and the market are the two main means for resource allocation, and both play important roles in economic development and environmental protection. Based on the theoretical mechanism analysis, this study empirically investigated the relationship between government intervention, market development, and China's provincial pollution emission efficiency by using the static panel OLS, system generalized method of moments (SYS-GMM), and panel threshold effect model during the period 2000-2017. The results show that the impact of government intervention on China's provincial pollution emission efficiency shows a non-linear U-shaped curve relationship, and there is a positive correlation between market development and provincial pollution emission efficiency in China. Government intervention and market development are complementary, rather than a substitute for each other, in promoting China's provincial pollution emission efficiency. When government intervention is set as the threshold variable, the impact of government intervention on China's provincial pollution emission efficiency shows the feature of "promotes first, then inhibits." However, when market development is set as the threshold variable, government intervention is only conducive to the improvement of China's provincial pollution emission efficiency at a moderate marketization level. Lastly, some policy implications related to the government and the market in enhancing China's provincial pollution emission efficiency are presented.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33226545

RESUMO

BACKGROUND: Although the use of direct oral anticoagulants (DOACs) has been reported in patients with atrial fibrillation (AF), there is currently no consensus on the occurrence or characteristics of the hemorrhage risk in different antithrombotic regimens. METHODS: Disproportionality and Bayesian analyses were performed in mining data of suspected hemorrhagic events after antithrombotic drug use from the FDA Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset and fatality rate of hemorrhage following different antithrombotic regimens were also compared. RESULTS: A total of 84,998 reports of hemorrhage-related adverse events with the use of antithrombotic drugs were identified. The patients included were mostly from the Americas (80.87%) and Europe (13.22%), with most data submitted by nonhealthcare professionals. Among the seven antithrombotic drug monotherapies, betrixaban had the highest association with hemorrhage based on the highest reporting odds ratio (ROR, 829.95; 95% CI = 113.61-6063.15), proportional reporting ratio (PRR, 24.68, χ2 = 804.24), and multi-item gamma Poisson shrinker (MGPS, 24.68, 95% one-sided CI = 4.67). The combination therapies of clopidogrel plus new oral anticoagulants had higher RORs, PRRs, and empirical Bayesian geometric means (EBGMs) than the antithrombotic drug monotherapies. Hemorrhage associated with rivaroxaban plus clopidogrel appeared to have an earlier onset (171 days vs 219 days, 95% two-sided CI =68.68-27.34, p < 0.0001) and a lower fatality rate (15.30% vs 17.74%, p<0.05) than that associated with rivaroxaban monotherapy. CONCLUSION: This study provides a relevant overview of the hemorrhagic complications/fatalities associated with different antithrombotic regimens in their real-world use. Among the combination therapies, clopidogrel plus DOACs were found to have stronger associations with hemorrhage than traditional dual antithrombotic therapies. Rivaroxaban showed a stronger association with hemorrhage than other antithrombotic drug monotherapies, and apixaban monotherapy appeared to have weaker associations with hemorrhage than others.

12.
Proc Natl Acad Sci U S A ; 117(47): 29535-29542, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33168731

RESUMO

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The "Beautiful China" strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 µg/m3 or below for annual mean concentration of PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO2 mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM2.5 target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO2 emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO2 mitigation, attributed particularly to the cost-effective reduction in household PM2.5 exposure. The additional low-carbon energy polices required for China's air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.

13.
Chin Med J (Engl) ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33156008

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. METHODS: We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, < 25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance. RESULTS: Overall, 4496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1094 NSYM, and 2837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100 person-year (PY), 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100 PY, and TDR prevalences were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age <21 years, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (adjusted [aOR]: 2.5; 95% CI: 1.0-5.8). CONCLUSIONS: College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

14.
Sci Total Environ ; : 143035, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33131864

RESUMO

To meet the food demands of a growing population, the maize production systems deployed by smallholders in China have tended towards extremely intensive planting and excessive use of fertilizers, which have caused serious environmental impacts. This study investigated the balance between the maize yield and nitrogen (N) input in the North China Plain (NCP), which is one of the most important grain-producing region in China. Our study compared yield simulations generated by the DSSAT-CERES-Maize model with actual data from a number of multi-site field experiments and an extensive household surveys encompassing 1671 farmers. The smallholders' maize cultivars, plant population, and amount of N input on the crop yield and how these affects the economic benefits were analyzed. The results showed that the average traditional farming methods' yield was 72% of the attainable yield, which means that farmers have ample room to improve their yields. We also found that the maize yields varied widely between farmers, and that most of them applied excessive amounts of N but failing to achieve an optimal yield due to poor fertilization management techniques. The study found that the economic benefits achieved by the farmers were low, but after deploying high-yield (HY) methods, the yield was increased by 34.9% and the economic benefits by 14.4%. The greenhouse gas (GHG) emissions associated with the traditional farming methods were high and could potentially be reduced by 48.6%. All in all, farmers should be given guidance on how to appropriately increase the plant population, reduce the input of N fertilizer, and optimize farmland management measures, so that China can achieve intensive but sustainable agricultural production at a lower environmental cost. It was concluded that there are still numerous biological and abiotic factors that restrict production increases by smallholders. These factors vary from region to region and require further investigation.

15.
Biochem Genet ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135088

RESUMO

Chalcone Isomerase (CHI) catalyzes the biosynthesis of flavonoids and secondary metabolism in plants. Currently, there is no systematic analysis of CHIs gene family in Fagaceae which is available. In this study, twenty-two CHI proteins were identified in five species of the Fagaceae family. The CHI superfamily in Fagaceae can be classified into three subfamilies and five groups using phylogenetic analysis, analysis of physicochemical properties, and structural prediction. Results indicated that serine (Ser) and isoleucine (Ile) residues determine the substrate preferred by active Type I Fagaceae CHI, and the chalcone isomerase-like (CHIL) of Fagaceae had active site residues. Adaptive analysis of CHIs showed that CHIs are subject to selection pressure. The active CHI gene of Fagaceae was located in the cytoplasm, and it had the typical gene structure of CHI and contains four exons. All the twenty-two identified CHIs had the conserved domain motif 3, and the different groups had their own structural characteristics. In the process of fatty acid binding protein (FAP) evolution to CHIL and CHI, the physical and chemical properties of proteins also had significant differences in addition to changes in protein functions.

16.
Langmuir ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33135416

RESUMO

Molecular bottlebrushes can exhibit a multitude of distinct conformations under different conditions, and precise control of their morphology can facilitate better use of such materials in potential applications. Herein, we report a study on the effect of buffer anions on the pearl-necklace morphology of linear binary heterografted molecular brushes consisting of pH-responsive poly(2-N,N-diethylamino)ethyl methacrylate) (PDEAEMA) with a pKa of 7.40 and thermoresponsive poly(ethoxydi(ethylene glycol) acrylate) (PDEGEA) with a lower critical solution temperature of 9 °C as side chains in various acidic aqueous buffers at 0 °C. The molecular brushes, denotated as BMB, were prepared by a grafting-to approach using copper(I)-catalyzed azide-alkyne cycloaddition reaction. Dynamic light scattering studies showed that the apparent hydrodynamic size of BMB in aqueous buffers with a pH of 6.50 at 1 °C decreased with increasing valency of buffer anions, from acetate anions with a charge of 1-, to phosphate anions carrying charges of 2- and 1- and citrate anions bearing charges of 3- and 2- at pH = 6.50. Atomic force microscopy revealed that BMB exhibited a pearl-necklace morphology from all three aqueous buffers with a pH of 6.50 when spin-cast at 0 °C. Analysis of AFM images showed that the average length of BMB and the number of beads per brush molecule decreased with increasing valency of buffer anions while the size and height of the beads increased. The pearl-necklace morphology of BMB was believed to be the result of microphase separation of the neutral PDEGEA and the charged PDEAEMA side chains along the brush backbone. Multivalent kosmotropic buffer anions formed bridging linkages between protonated tertiary amine moieties and thus "crosslinked" the charged PDEAEMA side chains, resulting in the shrinkage of BMB and enhanced microphase separation of two side chain polymers.

17.
Drug Alcohol Depend ; : 108381, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33158663

RESUMO

BACKGROUND: As the overdose emergency continues in British Columbia (BC), paramedic-attended overdoses are increasing, as is the proportion of people not transported to hospital following an overdose. This study investigated risk of death and subsequent healthcare utilization for people who were and were not transported to hospital after a paramedic-attended non-fatal overdose. METHODS: Using a linked administrative health data set which includes all overdoses that come into contact with health services in BC, we conducted a prospective cohort study of people who experienced a paramedic-attended non-fatal overdose between 2015 and 2016. People were followed for 365 days after the index event. The primary outcomes assessed were all-cause mortality and overdose-related death. Additionally, we examined healthcare utilization after the index event. RESULTS: In this study, 8659 (84%) people were transported and 1644 (16%) were not transported to hospital at the index overdose event. There were 279 overdose deaths (2.7% of people, 59.4% of deaths) during follow-up. There was no significant difference in risk of overdose-related death, though people not transported had higher odds of a subsequent non-fatal overdose event captured in emergency department and outpatient records within 90 days. People transported to hospital had higher odds of using hospital and outpatient services for any reason within 365 days. CONCLUSIONS: Transport to hospital after a non-fatal overdose is an opportunity to provide care for underlying and chronic conditions. There is a need to better understand factors that contribute to non-transport, particularly among people aged 20-59 and people without chronic conditions.

18.
J Phys Chem A ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124418

RESUMO

The present work investigates the calculation of S-matrix elements for six-atom reactions combining reduced-dimensional wave packet dynamics and the quantum transition-state framework. We employ the eight-dimensional (8D) model Hamiltonian developed by Palma and Clary [J. Chem. Phys. 2000, 112, 1859-1867] and reduce basis set sizes as well as the number of wave packets by exploiting space inversion and permutation symmetry. Mode-specific chemistry in the H2 + CH3 ⇆ H + CH4 reaction is studied with full quantum-state resolution. Results for the H + CH4 reaction are compared to full-dimensional benchmark results. Detailed state-to-state results for the H2 + CH3 reaction are presented for the first time. Although the "loss of memory" effect dominates for total energies up to 0.6 eV, more complex patterns emerge at higher energies. The agreement between the present reduced-dimensional and the accurate full-dimensional results is generally good. However, shortcomings in the reduced-dimensional model can also be noted. They are related to the description of the symmetric and asymmetric C-H stretch motion in the CH4 molecule.

19.
J Thorac Oncol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069888

RESUMO

INTRODUCTION: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study. METHODS: Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m2 plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progression-free survival (median: 24.5 versus 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35‒0.83) remained improved with pembrolizumab combination (n = 60) versus chemotherapy (n = 63), regardless of programmed death ligand 1 status. Median overall survival was 34.5 versus 21.1 months (hazard ratio: 0.71; 95% confidence interval: 0.45‒1.12), despite a 70% crossover rate from chemotherapy alone to anti‒programmed death (ligand) 1 therapy. Among the 12 patients who completed 2 years of pembrolizumab, 92% were alive at data cutoff; the estimated 3-year duration of response rate was 100%. Grade 3 to 5 treatment-related adverse events occurred in 39% of patients receiving pembrolizumab combination and 31% receiving chemotherapy. CONCLUSIONS: First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up.

20.
J Recept Signal Transduct Res ; : 1-8, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33100116

RESUMO

PURPOSE: This study mainly aimed to explore the influences of Calcium Voltage-Gated Channel Subunit Alpha1 B (CACNA1B) on the development of breast cancer and the related mechanism. MATERIALS AND METHODS: The information of patients with breast cancer from TCGA database was used for analyses of CACNA1B expression and its prognostic value. Loss- and gain- of functions of CACNA1B were conducted in MCF7 and Bcap-37 cells, respectively. CCK-8, colony formation and transwell assays were applied for evaluating the cell viability and motility. Western blot was used for protein expression detection. RESULTS: We revealed that highly expressed CACNA1B in breast cancer tissues was related to poor prognosis according to the data gained from TCGA database. The outcomes of functional assays showed that depletion of CACNA1B restrained MCF7 cell growth, invasion and migration and high-expression of CACNA1B fortified the growth, invasion and migration in Bcap-37 cells. Finally, we manifested that silencing CACNA1B obviously raised the protein expression level of E-cadherin and reduced the protein levels of Cyclin D1, N-cadherin and Snail in MCF7 cells, whilst, over-expression of CACNA1B reduced the level of E-cadherin and increased the expression of Cyclin D1, N-cadherin and Snail in Bcap-37 cells. CONCLUSIONS: These results identified CACNA1B as a forwarder of the growth, invasion and migration in breast cancer cells.

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