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1.
Sci Total Environ ; 785: 147303, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33933769

RESUMO

Peroxyacetyl nitrate (PAN) is the most important reservoir of nitrogen oxides, with effects on atmospheric oxidation capacity and regional nitrogen distribution. The first yearlong observational study of PAN was conducted from September 2018 to August 2019 at a suburban site and an urban site in Zhengzhou, Henan Province, central China. Compared with studies over the past two decades, summer PAN pollution at the suburban site and winter PAN pollution at both sites were more significant, with annual average concentrations of 1.96 ± 1.44 and 2.01 ± 1.59 ppbv, respectively. Seasonal PAN discrepancies between the urban and suburban areas were analyzed in detail. Active PAN formation, regional transport, photochemical precursors, and PAN lifetime played key roles during seasons with elevated PAN (winter and spring). According to the results of cluster analysis and potential source contribution function analysis, during the cold months, short-distance air mass transport from the east, south, and southeast of Henan Province and southern Hebei Province increased PAN pollution in urban Zhengzhou. PAN source areas were located in circumjacent industrial cities surrounding Zhengzhou except in the northeastern direction. Based on the relationships between pollutant concentrations, wind speed, and wind direction, a strong positive correlation between PAN and PM2.5 (and O3) existed in winter due to their joint transport. A slow-moving, low-height air mass passed through surrounding industrial cities before reaching the study area, carrying both pollutants and leading to strong consistency between PAN and O3 levels. The long-term PAN characteristics described in this study will help clarify the causes of regional air pollution in inland city agglomerations. Moreover, the PAN correlations and joint transport of PAN and PM2.5 (or O3) support the use of PAN as an indicator of air pollution introduced from surrounding industrial areas.

2.
Acta Pharmacol Sin ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33935286

RESUMO

We previously show that fatty acid-binding protein 3 (FABP3) triggers α-synuclein (Syn) accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model. But the role of fatty acid-binding protein 7 (FABP7) in the brain remains unclear. In this study we investigated whether FABP7 was involved in synucleinopathies. We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells, and treatment with arachidonic acid (100 M) significantly promoted FABP7-induced Syn aggregation, which was associated with cell death. We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid (ANS) assay; ligand 6 improved U251 cell survival via disrupting the FABP7-Syn interaction. We showed that activation of phospholipase A2 (PLA2) by psychosine (10 M) triggered oligomerization of endogenous Syn and FABP7, and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (1 M) significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death. This study demonstrates that FABP7 triggers α-synuclein oligomerization through oxidative stress, while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation, thereby rescuing glial cells and oligodendrocytes from cell death.

3.
Int J Biol Sci ; 17(6): 1507-1520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907514

RESUMO

The severe cases of Coronavirus Disease 2019 (COVID-19) frequently exhibit excessive inflammatory responses, acute respiratory distress syndrome (ARDS), coagulopathy, and organ damage. The most striking immunopathology of advanced COVID-19 is cytokine release syndrome or "cytokine storm" that is attributable to the deficiencies in immune regulatory mechanisms. CD4+FoxP3+ regulatory T cells (Tregs) are central regulators of immune responses and play an indispensable role in the maintenance of immune homeostasis. Tregs are likely involved in the attenuation of antiviral defense at the early stage of infection and ameliorating inflammation-induced organ injury at the late stage of COVID-19. In this article, we review and summarize the current understanding of the change of Tregs in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the potential role of Tregs in the immunopathology of COVID-19. The emerging concept of Treg-targeted therapies, including both adoptive Treg transfer and low dose of IL-2 treatment, is introduced. Furthermore, the potential Treg-boosting effect of therapeutic agents used in the treatment of COVID-19, including dexamethasone, vitamin D, tocilizumab and sarilumab, chloroquine, hydroxychloroquine, azithromycin, adalimumab and tetrandrine, is discussed. The problems in the current study of Treg cells in COVID-19 and future perspectives are also addressed.

4.
Nat Commun ; 12(1): 2464, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927201

RESUMO

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

5.
Nutr Metab Cardiovasc Dis ; 31(5): 1454-1466, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33810955

RESUMO

BACKGROUND AND AIMS: Host-microbiota interactions involving metabolic pathways have been linked to the pathogenesis of atherosclerotic disease and type 2 diabetes. As stable coronary artery disease (SCAD) patients combined with type 2 diabetes have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development. METHODS AND RESULTS: We used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined with diabetes mellitus (SCAD + T2DM, n = 38), SCAD (n = 71), and healthy control (HC, n = 55). We linked microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers. We identified that bacterial and metabolic signatures varied significantly between SCAD and SCAD + T2DM groups. SCAD + T2DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Our study also addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. In addition, we found that specific bacterial taxa Ruminococcus torques [HR: 2.363 (08-4.56), P = 0.03] was predictive of cardiac survival outcomes. CONCLUSION: Overall, our study identified relationships between features of the gut microbiota (GM) and circulating metabolites, providing a new direction for future studies aiming to understand the host-GM interplay in atherosclerotic cardiovascular pathogenesis.

6.
Nat Nanotechnol ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875869

RESUMO

The success of semiconductor electronics is built on the creation of compact, low-power switching elements that offer routing, logic and memory functions. The availability of nanoscale optical switches could have a similarly transformative impact on the development of dynamic and programmable metasurfaces, optical neural networks and quantum information processing. Phase-change materials are uniquely suited to enable their creation as they offer high-speed electrical switching between amorphous and crystalline states with notably different optical properties. Their high refractive index has already been harnessed to fashion them into compact optical antennas. Here, we take the next important step, by showing electrically-switchable phase-change antennas and metasurfaces that offer strong, reversible, non-volatile, multi-phase switching and spectral tuning of light scattering in the visible and near-infrared spectral ranges. Their successful implementation relies on a careful joint thermal and optical optimization of the antenna elements that comprise a silver strip that simultaneously serves as a plasmonic resonator and a miniature heating stage. Our metasurface affords electrical modulation of the reflectance by more than fourfold at 755 nm.

7.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731342

RESUMO

Adult neurogenesis in the dentate gyrus of the hippocampus is regulated by specific microglia groups and functionally implicated in behavioral responses to stress. However, the role of microglia in hippocampal neurogenesis and stress resilience remains unclear. We identified interleukin 4 (IL4)-driven microglia characterized by high expression of Arg1, which is critical in maintaining hippocampal neurogenesis and stress resistance. Decreasing Arg1+ microglia in the hippocampus by knocking down the microglial IL4R suppressed hippocampal neurogenesis and enhanced stress vulnerability. Increasing Arg1+ microglia in the hippocampus by enhancing IL4 signaling restored hippocampal neurogenesis and the resilience to stress-induced depression. Brain-derived neurotrophic factor (BDNF) was found necessary for the proneurogenesis effects of IL4-driven microglia. Together, our findings suggest that IL4-driven microglia in the hippocampus trigger BDNF-dependent neurogenesis responding to chronic stress, helping protect against depressive-like symptoms. These findings identify the modulation of a specific microglial phenotype as a treatment strategy for mood disorders.

8.
Pancreatology ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33712388

RESUMO

BACKGROUND: FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel (AG) regimens are recommended as first-line therapy for both locally advanced and metastatic pancreatic cancer. However, there were no specific markers to conduct personalized regimen choice. The research is to assess delta Housfield unit (delta HU), which is the difference in CT attenuation value (in HU) between enhanced and nonenhanced phase of region of interest, as a marker for predicting chemotherapy response of unresectable pancreatic cancer. METHODS: A total of 179 unresectable pancreatic cancer patients were enrolled in the study. Kaplan-Meier analysis and COX regression analysis were performed for progression-free survival (PFS) and overall survival. The differences of clinical characteristics were analyzed by χ 2test. Microvessel density (MVD) was calculated by immunochemistry staining of CD34. RESULTS: Delta HU was an independent risk factor for unresectable pancreatic cancer (P = 0.017, HR 0.672, 95%CI 0.485-0.930). Patients with higher delta HU were associated with better PFS (P = 0.004). For modified FOLFIRINOX (mFOLFIRINOX) group, delta HU was an independent risk factor (P = 0.045, HR 0.571), but not for AG group (P = 0.473, HR 0.855). Delta HU was correlated with stroma MVD (P = 0.000, R = 0.483), not with parenchyma MVD (P = 0.074, R = 0.199). CONCLUSIONS: Delta HU was a marker predicting chemotherapy response for unresectable pancreatic cancer. Higher delta HU was associated with better survival for patients receiving mFOLFIRINOX rather than AG. The delta HU was positively correlated with stroma MVD, explaining the relationship between delta HU and prognosis.

9.
Pharm Res ; 38(3): 479-490, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33646504

RESUMO

PURPOSE: Fatty acid-binding protein 7 (FABP7) involved in intracellular lipid dynamics, is highly expressed in melanomas and associated with decreased patient survival. Several studies put FABP7 at the center of melanoma cell proliferation. However, the underlying mechanisms are not well deciphered. This study examines the effects of FABP7 on Wnt/ß-catenin signaling that enhances proliferation in melanoma cells. METHODS: Skmel23 cells with FABP7 silencing and Mel2 cells overexpressed with wild-type FABP7 (FABP7wt) and mutated FABP7 (FABP7mut) were used. Cell proliferation and migration were analyzed by proliferation and wound-healing assay, respectively. Transcriptional activation of the Wnt/ß-catenin signaling was measured by luciferase reporter assay. The effects of a specific FABP7 inhibitor, MF6, on proliferation, migration, and modulation of the Wnt/ß-catenin signaling were examined. RESULTS: FABP7 siRNA knockdown in Skmel23 decreased proliferation and migration, cyclin D1 expression, as well as Wnt/ß-catenin activity. Similarly, FABP7wt overexpression in Mel2 cells increased these effects, but FABP7mut abrogated these effects. Pharmacological inhibition of FABP7 function with MF6 suppressed FABP7-regulated proliferation of melanoma cells. CONCLUSION: These results suggest the importance of the interaction between FABP7 and its ligands in melanoma proliferation modulation, and the beneficial implications of therapeutic targeting of FABP7 for melanoma treatment.

10.
Sci Adv ; 7(7)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568470

RESUMO

Through an integrative analysis of the lincRNA expression and tumor immune response in 9,626 tumor samples across 32 cancer types, we developed a lincRNA-based immune response (LIMER) score that can predict the immune cells infiltration and patient prognosis in multiple cancer types. Our analysis also identified tumor-specific lincRNAs, including EPIC1, that potentially regulate tumor immune response in multiple cancer types. Immunocompetent mouse models and in vitro co-culture assays demonstrated that EPIC1 induces tumor immune evasion and resistance to immunotherapy by suppressing tumor cell antigen presentation. Mechanistically, lincRNA EPIC1 interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of IFNGR1, TAP1/2, ERAP1/2, and MHC-I genes. Genetic and pharmacological inhibition of EZH2 abolish EPIC1's immune-related oncogenic effect and its suppression of interferon-γ signaling. The EPIC1-EZH2 axis emerges as a potential mechanism for tumor immune evasion that can serve as therapeutic targets for immunotherapy.

11.
Science ; 371(6536): 1374-1378, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33602867

RESUMO

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.


Assuntos
Antivirais/farmacologia , /antagonistas & inibidores , Inibidores de Proteases/farmacologia , Animais , Antivirais/química , Antivirais/uso terapêutico , /virologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL10/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Humanos , Interferon beta/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Oligopeptídeos , Prolina/análogos & derivados , Inibidores de Proteases/química , Inibidores de Proteases/uso terapêutico , Inibidores de Proteases/toxicidade , Ratos , Ratos Sprague-Dawley , Carga Viral/efeitos dos fármacos , Replicação Viral
12.
Breast Cancer Res Treat ; 187(1): 69-80, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33630196

RESUMO

PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.

13.
Chem Biol Interact ; 338: 109371, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33582112

RESUMO

Hepatocellular carcinoma (HCC) is one of the most deadly malignancies worldwide. However, current therapeutic drugs for HCC are far from satisfactory. Thus, the development of new drugs is urgently needed. In this study, we identified a novel quinazoline derivative, 04NB-03, with potent anti-HCC activities both in vitro and in vivo. 04NB-03 effectively suppressed the viability and proliferation of HCC cells. It induced both cell cycle arrest at the G2/M phase and apoptosis in concentration- and time-dependent manners. Moreover, 04NB-03 treatment significantly reduced xenograft tumor growth without notable toxic effects. Mechanistically, 04NB-03 induced endogenous reactive oxygen species (ROS) accumulation in concentration- and time-dependent manners. Scavenging the ROS reversed 04NB-03-induced cell cycle arrest and apoptosis. Taken together, these results indicate that the quinazoline derivative, 04NB-03, inhibits the growth of HCC cells through the induction of cell cycle arrest and apoptosis in an ROS-dependent manner. 04NB-03 is, therefore, a potential small molecule candidate for the development of antitumor drugs targeting HCC.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Quinazolinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quinazolinas/química
14.
Clin Cancer Res ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619171

RESUMO

PURPOSE: Patients with relapsed pediatric solid malignancies have few therapeutic options, and many of these patients die of their disease. B7-H3 is an immune checkpoint protein encoded by the CD276 gene that is overexpressed in many pediatric cancers. Here, we investigate the activity of the B7-H3-targeting antibody-drug conjugate (ADC) m276-SL-PBD in pediatric solid malignancy patient-derived (PDX) and cell line-derived xenograft (CDX) models. EXPERIMENTAL DESIGN: B7-H3 expression was quantified by RNA sequencing and by IHC on pediatric PDX microarrays. We tested the safety and efficacy of m276-SL-PBD in two stages. Randomized trials of m276-SL-PBD of 0.5 mg/kg on days 1, 8, and 15 compared with vehicle were performed in PDX or CDX models of Ewing sarcoma (N = 3), rhabdomyosarcoma (N = 4), Wilms tumors (N = 2), osteosarcoma (N = 5), and neuroblastoma (N = 12). We then performed a single mouse trial in 47 PDX or CDX models using a single 0.5 m/kg dose of m276-SL-PBD. RESULTS: The vast majority of PDX and CDX samples studied showed intense membranous B7-H3 expression (median H-score 177, SD 52). In the randomized trials, m276-SL-PBD showed a 92.3% response rate, with 61.5% of models showing a maintained complete response (MCR). These data were confirmed in the single mouse trial with an overall response rate of 91.5% and MCR rate of 64.4%. Treatment-related mortality rate was 5.5% with late weight loss observed in a subset of models dosed once a week for 3 weeks. CONCLUSIONS: m276-SL-PBD has significant antitumor activity across a broad panel of pediatric solid tumor PDX models.

15.
Oncoimmunology ; 10(1): 1868122, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33537172

RESUMO

Recent advances in immunotherapy, as a part of the multidisciplinary therapy, has gradually gained more attention. However, only a small proportion of patients who sensitive to the therapy could gain benefits. An increasing number of studies indicate that intestinal microbiota could enhance the efficiency of cancer immunotherapy. As one of the main probiotics, Bifidobacterium plays an important role in immune regulation, which has been proved by animal research and human clinical study. But the detailed mechanism was not clearly elucidated. Here we found oral administration of Bifidobacterium breve (B. breve) lw01 could significantly inhibit tumor growth and up-regulate tumor cell apoptosis, which relied on the recruitment of tumor-infiltrating lymphocytes and dendritic cells (DCs) in tumor microenvironment, but not Lactobacillus rhamnosus (L. rhamnosus) CGMCC 1.3724 or Escherichia coli (E. coli) MG1655. In the in situ ligated intestine loop model, B. breve's stimulation triggered the upregulated expression of DC-related chemokine CCL20 and recruited more DCs in the intestinal villi. Further study revealed the enhancement of interleukin 12 (IL-12) secretion derived from DCs is essential to B. breve's antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous B. breve might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via B. breve.

16.
Oncol Res Treat ; 44(3): 76-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33461197

RESUMO

OBJECTIVE: To identify patterns of therapy failure after radiotherapy in Chinese patients with locally advanced cervical cancer (LACC). METHODS: A retrospective study was conducted at a Chinese hospital from June 2012 to July 2018. All analyses were done using SPSS 26. RESULTS: 105 patients with treatment failure were included. After a median follow-up of 27 months (range 10-82), the 3-year survival rate after therapy failure was 19.4%. In multivariate analysis, squamous cell carcinoma antigen (SCC-Ag) <4 ng/mL (p < 0.001) and disease-free interval >12 months (p = 0.013) showed significant survival benefits. We identified 3 types of failure: distant lymph node metastasis (n = 50), hematogenous metastasis (n = 53) and pelvic failure (n = 48). Most metastatic para-aortic lymph nodes (PALN) were inferior to the level of left renal hilum (84.8%, n = 28). A total of 80% of patients with supraclavicular lymph nodes (SCLN) metastasis ignored imaging on supraclavicular region. For solitary SCLN or lung metastasis, the prognosis was better than that combined with other sites failure, respectively (p = 0.005; p = 0.001). Many patients with central sites recurrence received insufficient doses of intracavitary brachytherapy (IBT) for low tolerance to pain. CONCLUSION: The distribution of metastatic PALN is asymmetrical and optimizing clinical target volume to minimize toxicity of para-aortic radiation is necessary. The effect of ultrasonography as preliminary screening and follow-up means on SCLN metastasis can be expected. Pain management and psychological interventions are essential for patients receiving IBT.

17.
J Psychosom Res ; 142: 110366, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33494004

RESUMO

OBJECTIVE: We aim to provide early evidence of mental distress and its associated predictors among adults one month into the COVID-19 crisis in Brazil. METHODS: We conducted an online survey of 638 adults in Brazil on March 25-28, 2020, about one month (32 days) cross-sectionally after the first COVID-19 case in South America was confirmed in São Paulo. The 638 adults were in 25 states out of the 26 Brazilian states, with the only exception being Roraima, the least populated state in the Amazon. Of all the participating adults, 24%, 20%, and 18% of them were located in Rio de Janeiro state, Santa Catarina state, and São Paulo state respectively. RESULTS: In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less reported higher levels of distress. Each individual's distance from the Brazilian epicenter of São Paulo interacted with age and workplace attendance to predict the level of distress. The "typhoon eye effect" was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey. CONCLUSION: Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis.


Assuntos
/psicologia , Epidemias , Angústia Psicológica , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
18.
Chemosphere ; 263: 127563, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33296995

RESUMO

Bisphenol-A (BPA) has been widely used as a plasticizer in modern society and persistently released into aquatic environments. Herein, a novel Fe2O3-graphene oxide (GO) hybrid containing 22.8% of GO was prepared to enhance BPA removal from contaminated water and wastewater. This hybrid material afforded outstanding BPA adsorption capacities of 3293.9 mg g-1 under optimized conditions, which led to 1.9 times and 1.2 times of BPA removal as compared to GO and reduced GO (rGO), respectively. In addition, Fe2O3-GO showed higher thermal stability, greater solid/liquid separation performance, and better anti-fouling performance. Moreover, the coexistence of natural or effluent organic matter caused 6.7-16.8% decline in BPA adsorption capacity of Fe2O3-GO, which was lower than those of GO and rGO (11.8-39.4%). Further characterization experiments revealed that BPA removal by Fe2O3-GO was enhanced because of the formation of Lewis acid-base (AB) interactions between the active sites on Fe2O3 (Lewis base) and BPA anions (Lewis acid). The existence of the AB interaction is beneficial for practical application considering the low environmental concentrations of BPA in water and wastewater. Besides, the distinctly lowered GO content of the hybrid saved 77.2% of the adsorbent cost. In conclusion, this study demonstrated the potential of Fe2O3-GO as a novel material for the treatment of BPA-contaminated water and wastewater.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Grafite , Águas Residuárias , Água
19.
J Hazard Mater ; 403: 123860, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264935

RESUMO

Environmental-friendly solar photocatalytic technology is attracting great attention in the field of pollution control. In this work, novel PO43--Bi2WO6/PI photocatalyst achieved high degradation efficiency for tetracycline degradation in simulated solar light (1.6 times kinetic constants of Bi2WO6). The photocatalyst could produce more oxygen vacancies as well as more active species O2- and OH, and exhibited high mineralization ability, good stability and recyclability simultaneously. After 4 cycles of degradation experiments, its degradation efficiency was only reduced by 8.6 %. Tetracycline molecules gradually became small molecules under the attack of active species. The tetracycline degradation was highly pH-dependent and enhanced with the increase of solution pH. The water quality parameters humic acid and Cl- presented the inhibitory effect, while HCO3- can accelerate the tetracycline degradation. The degradation of tetracycline by PO43--Bi2WO6/PI conformed to the Z-scheme photocatalysis mechanism, which could effectively broaden the absorption of solar light, improve the separation and transfer of photogenerated electron-hole pairs and extend the lifespan of the photocatalyst.

20.
J Med Chem ; 64(1): 861-870, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33378197

RESUMO

Retinoid X receptor (RXR) modulators (rexinoids) are considered to have therapeutic potential for multiple diseases, such as Alzheimer's disease and Parkinson's disease. To overcome various disadvantages of prior screening methods, we previously developed an RXR binding assay using a fluorescent RXR ligand, CU-6PMN (4). However, this ligand binds not only at the ligand-binding domain (LBD) but also at the dimer-dimer interface of hRXRα. Here, we present a new fluorescent RXR antagonist 6-[N-ethyl-N-(5-isobutoxy-4-isopropyl-2-(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxamido)phenyl)amino]nicotinic acid (NEt-C343, 7), which emits strong fluorescence only when bound to the RXR-LBD. It allows us to perform a rapid, simple, and nonhazardous binding assay that does not require bound/free separation and uses a standard plate reader. The obtained Ki values of known compounds were correlated with the Ki values obtained using the standard [3H]9cis-retinoic acid assay. This assay should be useful for drug discovery as well as for research on endocrine disruptors, functional foods, and natural products.


Assuntos
Niacina/química , Receptores X Retinoide/antagonistas & inibidores , Sítios de Ligação , Humanos , Cinética , Ligantes , Simulação de Acoplamento Molecular , Niacina/metabolismo , Niacina/farmacologia , Ligação Proteica , Receptores X Retinoide/genética , Receptores X Retinoide/metabolismo , Espectrometria de Fluorescência , Ativação Transcricional/efeitos dos fármacos
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