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1.
Chemistry ; 30(37): e202401250, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38705864

RESUMEN

9,9-Dimethyl-9,10-dihydroacridine (DMAC) is one of the most widely used electron donor for constructing high-performance thermally activated delayed fluorescence (TADF) emitters. However, DMAC-based emitters often suffer from the imperfect color purity, particularly in blue emitters, due to its strong electron-donating capability. To modulate donor strength, 2,7-F-Ph-DMAC and 2,7-CF3-Ph-DMAC were designed by introducing the electron-withdrawing 2-fluorophenyl and 2-(trifluoromethyl)phenyl at the 2,7-positions of DMAC. These donors were used, in combination with 2,4,6-triphenyl-1,3,5-triazine (TRZ) acceptor, to develop novel TADF emitters 2,7-F-Ph-DMAC-TRZ and 2,7-CF3-Ph-DMAC-TRZ. Compared to the F- or CF3-free reference emitter, both two emitters showed hypsochromic effect in fluorescence and comparable photoluminescence quantum yields without sacrificing the reverse intersystem crossing rate constants. In particular, 2,7-CF3-Ph-DMAC-TRZ based OLED exhibited a blue shift by up to 39 nm and significantly improved Commission International de l'Éclairage (CIE) coordinates from (0.36, 0.55) to (0.22, 0.41), while the external quantum efficiency kept stable at about 22.5 %. This donor engineering strategy should be valid for improving the color purity of large amount of acridine based TADF emitters. It can be predicted that pure blue TADF emitters should be feasible if these F- or CF3-modifed acridine donors are combined with other weaker electron acceptors.

2.
Environ Sci Technol ; 58(29): 12865-12874, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38995089

RESUMEN

Short-term exposure to PM2.5 or O3 can increase mortality risk; however, limited studies have evaluated their interaction. A multicity time series study was conducted to investigate the synergistic effect of PM2.5 and O3 on mortality in China, using mortality data and high-resolution pollutant predictions from 272 cities in 2013-2015. Generalized additive models were applied to estimate associations of PM2.5 and O3 with mortality. Modification and interaction effects were explored by stratified analyses and synergistic indexes. Deaths attributable to PM2.5 and O3 were evaluated with or without modification of the other pollutant. The risk of total nonaccidental mortality increased by 0.70% for each 10 µg/m3 increase in PM2.5 when O3 levels were high, compared to 0.12% at low O3 levels. The effect of O3 on total nonaccidental mortality at high PM2.5 levels (1.26%) was also significantly higher than that at low PM2.5 levels (0.59%). Similar patterns were observed for cardiovascular or respiratory diseases. The relative excess risk of interaction and synergy index of PM2.5 and O3 on nonaccidental mortality were 0.69% and 1.31 with statistical significance, respectively. Nonaccidental deaths attributable to short-term exposure of PM2.5 or O3 when considering modification of the other pollutant were 28% and 31% higher than those without considering modification, respectively. Our results found synergistic effects of short-term coexposure to PM2.5 and O3 on mortality and suggested underestimations of attributable risks without considering their synergistic effects.


Asunto(s)
Contaminantes Atmosféricos , Ciudades , Ozono , Material Particulado , China/epidemiología , Humanos , Contaminantes Atmosféricos/toxicidad , Exposición a Riesgos Ambientales , Mortalidad
3.
Anim Biotechnol ; : 2387015, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145993

RESUMEN

Intestinal microbial community plays an important part in maintaining health and skeletal muscle development in livestock. This study is the first of its kind in the world. In order to better understand the relationship between gut microbiota and gene expression in skeletal muscle of rabbits, caecum contents and longissimus dorsi tissues of rabbits at 0 d (S1), 35 d (S2) and 70d (S3) were collected and subjected for 16S rRNA sequencing and transcriptome sequencing. Our results showed that, among three groups of rabbits, Firmicutes and Bacteroidetes were the dominant phyla at the phylum level, while Akmansia, Bacteroides and Ruminobacter were the dominant genera at the genus level, and the relative abundance of Akmansia and Bacteroides increased firstly and then decreased from 0 d to 70 d. By analyzing the transcriptome sequencing data, we identified 2866, 2446 and 4541 differentially expressed genes (DEGs) in S1 vs S2, S2 vs S3 and S1 vs S3 groups, respectively. Finally, we performed correlation analysis between gut microbiota and the expression levels of muscle development-related genes of rabbits at 0 d and 70 d. Compared with 0 day old rabbits, in 70 day old rabbits Acinetobacter and Cronbacter with decreased abundance, and Ruminococcaceae_UCG-014 and Ruminococcus_1 with increase abundance is beneficial to caecum health in rabbits. These results will lay a foundation for further re-searches about the relationship between caecum microflora and muscle development in rabbits.

4.
Circulation ; 145(24): 1749-1760, 2022 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-35450432

RESUMEN

BACKGROUND: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality from acute coronary syndrome (ACS); however, the associations of subdaily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. METHODS: We conducted a time-stratified case-crossover study among 1 292 880 patients with ACS from 2239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM2.5), coarse particulate matter (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. RESULTS: Acute exposures to PM2.5, NO2, SO2, and CO were each associated with the onset of ACS and its subtypes. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15 to 29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM2.5 (36.0 µg/m3), NO2 (29.0 µg/m3), SO2 (9.0 µg/m3), and CO (0.6 mg/m3) over the 0 to 24 hours before onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. NO2 showed the strongest associations with all 3 subtypes, followed by PM2.5, CO, and SO2. Greater magnitude of associations was observed among patients older than 65 years and in the cold season. Null associations of exposure to either PM2.5-10 or O3 with ACS onset were observed. CONCLUSIONS: The results suggest that transient exposure to the air pollutants PM2.5, NO2, SO2, or CO, but not PM2.5-10 or O3, may trigger the onset of ACS, even at concentrations below the World Health Organization air quality guidelines.


Asunto(s)
Síndrome Coronario Agudo , Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Síndrome Coronario Agudo/epidemiología , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Monóxido de Carbono/análisis , Monóxido de Carbono/toxicidad , China/epidemiología , Ciudades/epidemiología , Estudios Cruzados , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/toxicidad , Ozono/análisis , Ozono/toxicidad , Material Particulado/análisis , Material Particulado/toxicidad , Dióxido de Azufre/análisis , Dióxido de Azufre/toxicidad , Factores de Tiempo
5.
Soft Matter ; 19(3): 430-435, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36541446

RESUMEN

A chiral small molecule gelator (R)-H3L based on 1,1'-bi-2,2'-naphthol (BINOL)-phosphoric acid was designed and prepared, which spontaneously forms a stable water-induced gel. The gelation mechanism was revealed by single crystal X-ray diffraction analysis and a number of spectroscopic methods. Addition of Cu2+ improved the gelation ability, and the resultant metal organic gel realized visual enantioselective and chemoselective recognition toward L-histidine from enantiomers of 19 amino acids via gel collapse. The gel showed a highly sensitive response to L-histidine, and as low as 0.01 equiv. of L-histidine relative to the critical gelation concentration of (R)-H3L-Cu caused the gel to collapse. This strategy of regulating the assembly behavior through the interaction of amino acids and metal ions not only provides a simple and direct way to distinguish enantiomers, but also provides insight into how metal ions regulate the organization of biological supramolecular systems.


Asunto(s)
Histidina , Naftoles , Histidina/química , Naftoles/química , Estereoisomerismo , Aminoácidos/química , Aminas , Metales
6.
J Org Chem ; 88(1): 211-217, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36525553

RESUMEN

A highly chemoselective and enantioselective fluorescent probe has been discovered for the recognition of prolinol among various primary and secondary amine-based amino alcohols. The mechanistic studies including 1D and 2D 1H/13C NMR and mass spectroscopic analyses and DFT calculations have shown that the aldehyde group of the probe can react with prolinol to generate a bicyclic oxazolidine unit which, through a possible intramolecular hydrogen bond interaction, will lead to highly selective fluorescence enhancement.


Asunto(s)
Aminas , Colorantes Fluorescentes , Estereoisomerismo , Colorantes Fluorescentes/química , Pirrolidinas
7.
CMAJ ; 195(17): E601-E611, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37127306

RESUMEN

BACKGROUND: Few studies have explored the relationship between air pollution and arrhythmia onset at the hourly level. We aimed to examine the association of exposure to air pollution with the onset of acute symptomatic arrhythmia at an hourly level. METHODS: We conducted a nationwide, time-stratified, case-crossover study in China between 2015 and 2021. We obtained hourly information on the onset of symptomatic arrhythmia (including atrial fibrillation, atrial flutter, atrial and ventricular premature beats and supraventricular tachycardia) from the Chinese Cardiovascular Association Database - Chest Pain Center (including 2025 certified hospitals in 322 cities). We obtained data on hourly concentrations of 6 air pollutants from the nearest monitors, including fine particles (PM2.5), coarse particles (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone. For each patient, we matched the case period to 3 or 4 control periods during the same hour, day of week, month and year. We used conditional logistic regression models to analyze the data. RESULTS: We included a total of 190 115 patients with acute onset of symptomatic arrhythmia. Air pollution was associated with increased risk of onset of symptomatic arrhythmia within the first few hours of exposure; this risk attenuated substantially after 24 hours. An interquartile range increase in PM2.5, NO2, SO2 and CO in the first 24 hours after exposure (i.e., lag period 0-24 h) was associated with significantly higher odds of atrial fibrillation (1.7%-3.4%), atrial flutter (8.1%-11.4%) and supraventricular tachycardia (3.4%-8.9%). Exposure to PM2.5-10 was associated with significantly higher odds of atrial flutter (8.7%) and supraventricular tachycardia (5.4%), and exposure to ozone was associated with higher odds of supraventricular tachycardia (3.4%). The exposure-response relationships were approximately linear, without discernible concentration thresholds. INTERPRETATION: Exposure to air pollution was associated with the onset of symptomatic arrhythmia shortly after exposure. This finding highlights the importance of further reducing air pollution and taking prompt protective measures for susceptible populations during periods of elevated levels of air pollutants.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Fibrilación Atrial , Aleteo Atrial , Ozono , Humanos , Estudios Cruzados , Fibrilación Atrial/inducido químicamente , Ciudades , Aleteo Atrial/inducido químicamente , Dióxido de Nitrógeno , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Ozono/análisis , China , Exposición a Riesgos Ambientales/efectos adversos
8.
Environ Sci Technol ; 57(7): 2856-2863, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36757895

RESUMEN

Changes in human genome-wide long noncoding RNAs (lncRNAs) associated with air pollution are unknown. This study aimed to investigate the effect of air pollution on human exosomal lncRNAs. A randomized, crossover trial was conducted among 35 healthy adults. Participants were allocated to 4 h exposure in road (high air pollution) and park (low air pollution) sessions in random order with a 2 week washout period. RNA sequencing was performed to measure lncRNAs. Differential lncRNAs were identified using a linear mixed-effect model. Mean concentrations of air pollutants such as ultrafine particles (UFP), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were 2-3 times higher in the road than those in the park. Fifty-five lncRNAs [false discovery rate (FDR) < 0.05] including lncRNA NORAD, MALAT1, and H19 were changed in response to air pollution exposure. We found that 54 lncRNAs were associated with CO, 49 lncRNAs with UFP, 49 lncRNAs with BC, 48 lncRNAs with NO2, and 4 lncRNAs with PM2.5 (FDR < 0.05). These differential lncRNAs participated in dozens of pathways including cardiovascular signaling, epithelial cell proliferation, inflammation, and transforming growth factor. This trial for the first time profiled changes of human exosomal lncRNAs following air pollution. Our findings revealed multiple biological processes moderated by lncRNAs and provided epigenetic insights into cardiovascular effects of air pollution.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , ARN Largo no Codificante , Adulto , Humanos , ARN Largo no Codificante/genética , Dióxido de Nitrógeno/análisis , Exposición a Riesgos Ambientales/análisis , Estudios Cruzados , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/análisis
9.
Environ Sci Technol ; 57(4): 1701-1711, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36668989

RESUMEN

Associations between ultrafine particles (UFPs) and hourly onset of acute myocardial infarction (AMI) have rarely been investigated. We aimed to evaluate the impacts of UFPs on AMI onset and the lag patterns. A time-stratified case-crossover study was performed among 20,867 AMI patients from 46 hospitals in Shanghai, China, between January 2015 and December 2020. Hourly data of AMI onset and number concentrations of nanoparticles of multiple size ranges below 0.10 µm (0.01-0.10, UFP/PNC0.01-0.10; 0.01-0.03, PNC0.01-0.03; 0.03-0.05, PNC0.03-0.05; and 0.05-0.10 µm, PNC0.05-0.10) were collected. Conditional logistic regressions were applied. Transient exposures to these nanoparticles were significantly associated with AMI onset, with almost linear exposure-response curves. These associations occurred immediately after exposure, lasted for approximately 6 h, and attenuated to be null thereafter. Each interquartile range increase in concentrations of total UFPs, PNC0.01-0.03, PNC0.03-0.05, and PNC0.05-0.10 during the preceding 0-6 h was associated with increments of 3.29, 2.08, 2.47, and 2.93% in AMI onset risk, respectively. The associations were stronger during warm season and at high temperatures and were robust after adjusting for criteria air pollutants. Our findings provide novel evidence that hourly UFP exposure is associated with immediate increase in AMI onset risk.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Infarto del Miocardio , Humanos , Material Particulado/análisis , Estudios Cruzados , Exposición a Riesgos Ambientales/análisis , China/epidemiología , Contaminantes Atmosféricos/análisis , Infarto del Miocardio/epidemiología , Contaminación del Aire/análisis , Tamaño de la Partícula
10.
Eur Heart J ; 43(3): 228-235, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-34849712

RESUMEN

AIMS: The incidence of acute aortic dissection (AAD) has been shown to have seasonal variation, but whether this variation can be explained by non-optimum ambient temperature and temperature change between neighbouring days (TCN) is not clear. METHODS AND RESULTS: We performed a time-stratified case-crossover study in the Registry of Aortic Dissection in China covering 14 tertiary hospitals in 11 cities from 2009 to 2019. A total of 8182 cases of AAD were included. Weather data at residential address were matched from nearby monitoring stations. Conditional logistic regression model and distributed lag nonlinear model were used to estimate the associations of daily temperature and TCN with AAD, adjusting for possible confounders. We observed an increase of AAD risk with lower temperature cumulated over lag 0-1 day and this association became statistically significant when daily mean temperature was below 24°C. Relative to the referent temperature (28°C), the odds ratios (ORs) of AAD onset at extremely low (-10°C) and low (1°C) temperature cumulated over lag 0-1 day were 2.84 [95% confidence interval (CI): 1.69, 4.75] and 2.36 (95% CI: 1.61, 3.47), respectively. A negative TCN was associated with increased risk of AAD. The OR of AAD cumulated over lag 0-6 days was 2.66 (95% CI: 1.76, 4.02) comparing the extremely negative TCN (-7°C) to no temperature change. In contrast, a positive TCN was associated with reduced AAD risk. CONCLUSION: This study provides novel and robust evidence that low ambient temperature and temperature drop between neighbouring days were associated with increased risk of AAD onset. KEY QUESTION: Incidence of acute aortic dissection (AAD) was reported to have seasonal trends, but it remains unclear whether non-optimum ambient temperature and temperature change between neighbouring days (TCN) is associated with AAD onset. KEY FINDING: Daily mean temperature lower than 24°C was significantly associated with increased risk of AAD at lag 0-1 day. A negative TCN (temperature drop) was associated with increased risk of AAD, whereas a positive TCN was associated with decreased risk. TAKE HOME MESSAGE: This multi-centre, case-crossover study provides novel and robust evidence that low ambient temperature and temperature drop between neighbouring days were associated with increased AAD risk.


Asunto(s)
Disección Aórtica , Disección Aórtica/epidemiología , Disección Aórtica/etiología , China/epidemiología , Frío , Estudios Cruzados , Humanos , Estaciones del Año , Temperatura
11.
J Biol Chem ; 296: 100287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33450223

RESUMEN

Autophagy is vital for maintaining cellular homeostasis through removing impaired organelles. It has recently been found to play pivotal roles in diabetes mellitus (DM), which is associated with increased bone fracture risk and loss of bone density. However, the mechanism whereby autophagy modulates DM-induced bone loss is not fully elucidated. Previous work has shown that 1α,25-Dihydroxyvitamin D3 (1,25D) exerts positive effects on autophagy, thus affecting bone metabolism. Here, we investigated whether autophagy was involved in the regulation of diabetic bone metabolism. Using Micro-CT, Elisa, histology, and histomorphometry analysis, we demonstrated that 1,25D rescues glucose metabolism dysfunction and ameliorates bone loss in diabetic mice. In vitro, 1,25D alleviated primary osteoblast dysfunction and intracellular oxidative stress through reducing prolonged high-glucose-mediated excessive autophagy in primary osteoblasts, reflected by decreased protein level of Beclin1 and LC3. Of note, the autophagy activator rapamycin (RAP) ablated the positive effects of 1,25D in diabetic environment, leading to a marked increase in autolysosomes and autophagosomes, examined by mRFP-GFP-LC3 fluorescence double labeling. The excessive autophagy induced by high glucose was deleterious to proliferation and differentiation of primary osteoblasts. Additionally, biochemical studies identified that PI3K/Akt signaling could be activated by 1,25D, resulting in the inhibition of FoxO1. We confirmed that FoxO1 deficiency alleviated high-glucose-induced autophagy and improved biological functions of primary osteoblasts. Together, our results suggest that the PI3K/Akt/FoxO1 signaling pathway is involved in the osteoprotective effect of 1,25D by attenuating autophagy in diabetes, providing a novel insight for the prevention and treatment of diabetes-caused bone loss.


Asunto(s)
Autofagia/efectos de los fármacos , Calcitriol/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Proteína Forkhead Box O1/genética , Glucosa/metabolismo , Osteoporosis/tratamiento farmacológico , Animales , Autofagosomas/efectos de los fármacos , Autofagosomas/metabolismo , Autofagia/genética , Beclina-1/genética , Beclina-1/metabolismo , Densidad Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/patología , Proteína Forkhead Box O1/deficiencia , Regulación de la Expresión Génica , Glucosa/antagonistas & inhibidores , Glucosa/farmacología , Lisosomas/efectos de los fármacos , Masculino , Ratones , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/patología , Osteoporosis/inducido químicamente , Osteoporosis/genética , Osteoporosis/patología , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sirolimus/farmacología , Estreptozocina , Resultado del Tratamiento
12.
J Periodontal Res ; 57(3): 519-532, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35212419

RESUMEN

OBJECTIVE: The purpose of this study was to investigate whether soy isoflavone supplementation is effective in preventing periodontal destruction exacerbated by estrogen deficiency (ED) and its potential mechanism. BACKGROUND: The progression of periodontitis is affected by host factors, such as smoking, diabetes mellitus, and steroid use. Bone loss in periodontitis can be aggravated by ED. METHODS: A rat model of experimental periodontitis (EP) with ED was established by silk ligature and inoculation with Porphyromonas gingivalis, and some EP rats were subjected to bilateral ovariectomy (OVX). The treatment groups received an intravenous injection of 17-ß-estradiol (E2 B) or soy isoflavones (SI) by gavage. The rats were euthanized, and the maxillary jaws, gingiva, and serum were harvested. Tight junction protein and interleukin (IL)-17 expression, reactive oxygen species (ROS) level, and periodontal destruction were assessed. In addition, we determined whether grainyhead-like 2 (GRHL2) is required for enhancing the epithelial barrier by SI in an in vitro P. gingivalis infection model. RESULTS: Estrogen deficiency impaired the expression of genes encoding tight junction proteins in the gingiva, increased IL-17 level, and accelerated alveolar bone resorption. SI treatment alleviated tight junction protein expression, decreased IL-17 and ROS levels, and prevented the absorption of alveolar bone. Furthermore, GRHL2 expression was significantly induced by SI in human oral keratinocytes-1 (HOK-1) cells; GRHL2 knockdown impaired the expression of OCLN and ZO-1 induced by SI treatment. CONCLUSION: Soy isoflavones alleviates periodontitis in OVX rats, as observed by the increased expression of tight junction proteins, and reduced IL-17 level and alveolar bone loss. The in vitro studies suggested that the enhancement of oral epithelial barrier by SI treatment was partially dependent on GRHL2.


Asunto(s)
Pérdida de Hueso Alveolar , Isoflavonas , Periodontitis , Pérdida de Hueso Alveolar/prevención & control , Animales , Modelos Animales de Enfermedad , Estrógenos/uso terapéutico , Femenino , Humanos , Interleucina-17 , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Periodontitis/prevención & control , Ratas , Especies Reactivas de Oxígeno , Proteínas de Uniones Estrechas
13.
Environ Health ; 21(1): 104, 2022 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-36309727

RESUMEN

BACKGROUND: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects. METHODS: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups. RESULTS: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. CONCLUSION: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov (NCT03255187).


Asunto(s)
Contaminación del Aire , Aceites de Pescado , Material Particulado/efectos adversos , Suplementos Dietéticos , Método Doble Ciego , China , Contaminación del Aire/efectos adversos , Contaminación del Aire/prevención & control , Aceites de Plantas
14.
J Clin Pharm Ther ; 47(6): 798-808, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35229901

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Aflibercept, a recombinant protein designed to suppress the vascular endothelial growth factor (VEGF) signalling pathway, has been used in patients with metastatic colorectal cancer (mCRC). We conducted the first meta-analysis to systematically review the efficacy and safety of aflibercept in mCRC. METHODS: PubMed Central/Medline, Embase and cochrane library were systematically searched for randomized controlled trials and single-arm clinical trials on aflibercept plus chemotherapy for the treatment of mCRC through 9 September 2021. RESULTS: Ten studies comprising 2049 patients met the inclusion criteria. The pooled estimate rates were 16.0% for 12mPFS, 64.4% for 12mOS, 32.5% for ORR, 83.5% for DCR, while the rates of III/IV AEs rate were 80.2% respectively. The pooled estimate rates were 16.8% for III/IV diarrhoea, 22.3% for III/IV hypertension, 29.5% for III/IV neutropenia, 7.3% for III/IV proteinuria and 8.6% for III/IV oral mucositis. CONCLUSIONS: Analysis of data from randomized controlled trials(RCT) and single-arm clinical trials confirmed the good efficacy of aflibercept plus chemotherapy in mCRC, while the safety of the treatment is concerning.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular
15.
Zhongguo Zhong Yao Za Zhi ; 47(2): 484-491, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-35178993

RESUMEN

Amyloid ß-protein(Aß) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aß_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aß-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aß, and may reduce Aß-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.


Asunto(s)
Ginsenósidos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Ginsenósidos/farmacología , Humanos , Mitofagia/fisiología , Células PC12 , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Ratas , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
16.
Angew Chem Int Ed Engl ; 61(14): e202116927, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35104385

RESUMEN

Multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters show great potentials for high color purity organic light-emitting diodes (OLEDs). However, the simultaneous realization of high photoluminescence quantum yield (PLQY) and high reverse intersystem crossing rate (kRISC ) is still a formidable challenge. Herein, a novel asymmetric MR-TADF emitter (2Cz-PTZ-BN) is designed that fully inherits the high PLQY and large kRISC values of the properly selected parent molecules. The resonating extended π-skeleton with peripheral protection can achieve a high PLQY of 96 % and a fast kRISC of above 1.0×105  s-1 , and boost the performance of corresponding pure green devices with an outstanding external quantum efficiency (EQE) of up to 32.8 % without utilizing any sensitizing hosts. Remarkably, the device sufficiently maintains a high EQE exceeding 23 % at a high luminance of 1000 cd m-2 , representing the highest value for reported green MR-TADF materials at the same luminescence.

17.
J Cell Mol Med ; 25(8): 4148-4156, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33609082

RESUMEN

1ɑ,25-dihydroxyvitamin D3 (1,25D) and fibroblast growth factor 23 (FGF23) play important roles in bone metabolism through mutual regulation. However, the underlying mechanism between 1,25D and FGF23 in diabetes-induced bone metabolism disorders has not yet been elucidated. In this study, we investigated the effect of 1,25D on FGF23 under diabetic condition both in vitro and in vivo. The results showed that 1,25D down-regulated the expression of FGF23 in osteoblast significantly though a dose-dependent manner in vitro within high glucose environment. Western blot and immunofluorescence analysis indicated that 1,25D activated PI3K/Akt signalling through binding to vitamin D receptor (VDR), which inhibited the phosphorylation of the transcription factor Forkhead Box O1 (FOXO1). Decreased phosphorylation of FOXO1 down-regulated the expression Dickkopf-1 (DKK1), a well-known inhibitor of Wnt signalling. In addition, we observed that 1,25D remarkably ameliorated osteogenic phenotypic markers such as Ocn and Runx2 and rescued diabetes-induced bone loss in vivo. Our results suggested that 1,25D could promote osteogenesis though down-regulating FOXO1/FGF23 in diabetes.


Asunto(s)
Enfermedades Óseas Metabólicas/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Regulación de la Expresión Génica/efectos de los fármacos , Osteoblastos/citología , Osteogénesis , Vitamina D/análogos & derivados , Animales , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/patología , Células Cultivadas , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Masculino , Ratones , Osteoblastos/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/farmacología , Vía de Señalización Wnt
18.
J Org Chem ; 86(14): 9603-9609, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34165295

RESUMEN

A new red-light-emitting fluorescent probe (R)-5 was synthesized. In the presence of Zn2+, this compound was found to exhibit good enantioselective fluorescence enhancement at λ = 655 nm when treated with a variety of amino acids in aqueous solution. This probe in combination with a green-light-emitting probe (S)-4 that has enantioselective fluorescence enhancement at λ = 505 nm has formed a pseudoenantiomeric sensor pair because of their opposite enantioselectivities. This sensor pair can simultaneously detect both enantiomers of a chiral amino acid at two very different wavelengths (Δ = 150 nm). It was used to visually and semiquantitatively determine the enantiomeric compositions of amino acids. For example, when a 1:1 mixture of (R)-5 and (S)-4 was treated with Zn(OAc)2 and histidine samples of 0-100% [d-His], the color of the mixtures changed from green to yellow, orange, and red under a UV lamp (365 nm), which allowed a quick quantification of [d-His]%. This is the first example of using fluorescence to visually quantify the enantiomeric composition of chiral compounds.


Asunto(s)
Aminoácidos , Colorantes Fluorescentes , Aminas , Espectrometría de Fluorescencia , Estereoisomerismo
19.
Ecotoxicol Environ Saf ; 211: 111958, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33503545

RESUMEN

BACKGROUND: Accurate individual exposure assessment is crucial for evaluating the health effects of particulate matter (PM). Various portable monitors built upon low-cost optical sensors have emerged. However, the main challenge for their application is to guarantee accuracy of measurements. OBJECTIVE: To assess the performance of a newly developed PM sensor, and to develop methods for post-hoc data calibration to optimize its data quality. METHOD: We conducted a series of laboratory experiments and field evaluations to quantify the reproducibility within Plantower PM sensors 7003 (PMS 7003) and the consistency between sensors and two established PM2.5 measurement methods [tapered element oscillating microbalances (TEOM) and gravimetric method (GM)]. Post-hoc data calibration methods for sensors were based on a multiple linear regression model (MLRM) and a random forest model (RFM). Ratios of raw and calibrated readings over the data of reference methods were calculated to examine the improvement after calibration. RESULTS: Strong correlations (≥0.82) and relatively small relative standard deviations (16-21%) between sensors were found during the laboratory and the field sampling. Compared with the reference methods, moderate to strong coefficients of determination (0.56-0.83) were observed; however, significant deviations were presented. After calibration, the ratios of PMS measurements over that of two reference methods both became convergent. CONCLUSIONS: Our study validated low-cost optical PM sensors under a wide range of PM2.5 concentrations (8-167 µg/m3). Our findings indicated potential applicability of PM sensors in PM2.5 exposure assessment, and confirmed a need of calibration. Linear calibration methods may be sufficient for ambient monitoring using TEOM as a reference, while nonlinear calibration methods may be more appropriate for indoor monitoring using GM as a reference.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/instrumentación , Calibración , Monitoreo del Ambiente/métodos , Humanos , Laboratorios , Modelos Lineales , Material Particulado/análisis , Reproducibilidad de los Resultados
20.
J Org Chem ; 85(7): 4901-4905, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32148044

RESUMEN

The addition of Mg2+ is found to turn on the fluorescence response of a molecular probe, 3,3'-diformyl-1,1'-bi-2-naphthol, toward chiral amino acids with high enantioselectivity. It is further found that the enantioselective fluorescence responses of the molecular probe in the presence of Mg2+ toward certain amino acids are the opposite of those in the presence of Zn2+, that is, using Mg2+ with an l-amino acid generates much greater fluorescence enhancement than with the corresponding d-amino acid, but using Zn2+ with the d-amino acid gives much greater fluorescence than with the l-enantiomer. Thus, simply changing the metal cation additive allows the chirality sense of the fluorescence-based molecular recognition to be easily regulated.

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