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1.
Cell Death Discov ; 10(1): 224, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724500

RESUMEN

Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside's capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside's significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

2.
Bioresour Technol ; 387: 129685, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37595808

RESUMEN

Microbial lipids were produced through a two-stage process with Cryptococcus curvatus by co-fermenting rice and shrimp shells hydrolysates. In the first stage, biomass production of glucose and N-acetylglucosamine was optimized by response surface methodology with the maximum biomass yield (17.60 g/L) under optimum conditions (43.2 g/L mixed sugar concentration, pH 5.8, 200 rpm, and 28 °C). In the second stage, according to a single-factor optimization setting (43.2 g/L sugar mixture solutions, pH 5.5, and shift time of 36 h), lipid titer of 10.08 g/L with content of 55.30 % was achieved. Scaling up to a 5-L bioreactor increased lipid content to 60.07 % with 0.233 g/g yield. When Cryptococcus curvatus was cultured in the blends of rice hydrolysates and shrimp shells hydrolysate, lipid content and yield were 52.25 % and 0.204 g/g. The fatty acid compositions of lipid were similar to those of typical vegetable oils.


Asunto(s)
Oryza , Eliminación de Residuos , Glucosa , Alimentos , Acetilglucosamina , Fermentación , Ácidos Grasos
3.
Molecules ; 28(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37570771

RESUMEN

The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)n sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)n have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)n have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA-protein interactions or impeding the phase transition of r(GGGGCC)n. In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)n, its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)n and its influence on partner binding. Given the crucial role of r(GGGGCC)n in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)n RNA.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Humanos , Esclerosis Amiotrófica Lateral/metabolismo , Demencia Frontotemporal/genética , Secuencia de Bases , Expansión de las Repeticiones de ADN , ARN/genética , ARN/química , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
4.
J Drug Target ; 31(2): 217-224, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36214127

RESUMEN

OBJECTIVE: To design and construct a hydrogel drug-controlled release system loaded with gentamicin on a titanium surface, and to evaluate the in vitro drug release behaviour and antibacterial properties and biocompatibility of the controlled release system. METHODS: Titanium (Ti) surface was coated with poly dopamine (PDA) substrate, and then polyethylene glycol (PEG) was attached to PDA. The composite drug microsphere controlled release layer formed by gentamicin (GEN) and cross-linked starch (CSt) were subsequently covered with poly lactic⁃co⁃glycolic acid (PLGA) as a barrier to construct a Ti-GEN-Cst-PLGA anti-infective drug controlled release system. RESULTS: The hydrogel drug release system was successfully constructed. The results of in vitro anti-staphylococcus aureus (SAU) assay, anti-staphylococcus epidermidis (SEP) assay and anti-Escherichia coli (ECO) assay showed that Ti-GEN-Cst-PLGA could effectively inhibit the growth of three bacteria. Assay in the New Zealand rabbit found that Ti-GEN-Cst-PLGA could promote wound healing at the 3rd week after implantation, and the pathology assay found that the Ti-GEN-Cst-PLGA group had less inflammatory reactions and significant tissue proliferation at the endophyte contact surface. CONCLUSION: Ti-GEN-Cst-PLGA can effectively inhibit the inflammatory response and promote wound healing, or may be a potential treatment for orthopaedic endophytes.


Asunto(s)
Gentamicinas , Titanio , Animales , Conejos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Titanio/farmacología , Gentamicinas/farmacología , Preparaciones de Acción Retardada , Microesferas , Materiales Biocompatibles , Polietilenglicoles/química , Hidrogeles , Almidón/química
5.
Int Wound J ; 20(4): 1061-1071, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36111540

RESUMEN

We performed a meta-analysis to evaluate the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer. A systematic literature search up to July 2022 was performed and 10 231 subjects with cervical cancer at the baseline of the studies; 4307 of them were using the minimally invasive surgery, and 5924 were using laparotomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer using the dichotomous methods with a random or fixed-effect model. The minimally invasive surgery had significantly lower wound infection (OR, 0.20; 95% CI, 0.13-0.30, P < .001), and postoperative complications (OR, 0.48; 95% CI, 0.37-0.64, P < .001) in subjects with cervical cancer compared laparotomy. However, minimally invasive surgery compared with laparotomy in subjects with cervical cancer had no significant difference in intraoperative complications (OR, 1.04; 95% CI, 0.80-1.36, P = 0.76). The minimally invasive surgery had significantly lower wound infection, and postoperative complications however, had no significant difference in intraoperative complications in subjects with cervical cancer compared with laparotomy. The analysis of outcomes should be with caution because of the low sample size of 22 out of 41 studies in the meta-analysis and a low number of studies in certain comparisons.


Asunto(s)
Neoplasias del Cuello Uterino , Infección de Heridas , Femenino , Humanos , Neoplasias del Cuello Uterino/cirugía , Laparotomía/efectos adversos , Laparotomía/métodos , Complicaciones Posoperatorias/cirugía , Complicaciones Intraoperatorias , Infección de Heridas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos
6.
Nagoya J Med Sci ; 84(3): 506-515, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36237885

RESUMEN

We aimed to assess the effects of serratus anterior plane block (SAPB) and thoracic paravertebral nerve block (TPVB) on analgesia, immune function and serum tumor markers in patients after thoracoscopic radical resection of lung cancer. A total of 132 patients enrolled from February 2019 to November 2020 were prospectively selected and randomly divided into 3 groups (n=44). Control group received general anesthesia. After induction of general anesthesia, TPVB or SAPB group was given TPVB or SAPB. Their clinical data, operation conditions, Visual Analogue Scale (VAS) score, immune function, serum tumor markers and adverse reactions were compared. TPVB and SAPB groups had lower dosage of sufentanil during operation, later time of first pressing patient-controlled intravenous analgesia (PCA) pump after operation and smaller number of pressing PCA pump within 48 h after operation than those of control group (P<0.05). VAS scores at rest and coughing decreased 6 and 12 h after operation in TPVB and SAPB groups compared with that in control group (P<0.05). Cluster of differentiation 3 (CD3)+, CD4+ and CD4+/CD8+ ratio were higher, while CD8+ was lower 24 and 48 h after operation in TPVB and SAPB groups than those of control group (P<0.05). TPVB and SAPB groups had lower serum tumor marker levels 24 h after operation than those of control group (P<0.05). The three groups had similar incidence rates of adverse reactions (P>0.05). SAPB and TPVB can markedly improve postoperative analgesic effect, enhance immune function and decrease serum tumor marker levels in patients receiving thoracoscopic radical resection of lung cancer, without increasing adverse reactions. However, TPVB may puncture the pleura.


Asunto(s)
Neoplasias Pulmonares , Bloqueo Nervioso , Analgesia Controlada por el Paciente , Analgésicos/uso terapéutico , Biomarcadores de Tumor , Humanos , Inmunidad , Neoplasias Pulmonares/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Sufentanilo/uso terapéutico
7.
Front Public Health ; 10: 1024816, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36238253

RESUMEN

Background: In the context of global climate changes, increasing extreme weather events have aroused great public concern. Limited evidence has focused on the association between extreme precipitation and hospitalizations for acute myocardial infarction (AMI). Our study aimed to examine the effect of extreme precipitation on AMI hospitalizations. Methods: Daily AMI hospitalizations, weather variables and air pollution data in Beijing from 2013 to 2018 were obtained. We used a time-series analysis with a distributed lag model to evaluate the association of extreme precipitation (≥95th percentile of daily precipitation) with AMI hospitalizations. Subgroup analysis was conducted to identify the vulnerable subpopulations and further assessed the attributable burden. Results: Extreme precipitation increased the risk of AMI hospitalizations with significant single-day effects from Lag 4 to Lag 11, and the maximum cumulative effects at Lag 0-14 (CRR = 1.177, 95% CI: 1.045, 1.326). Older people (≥65 years) and females were more vulnerable to extreme precipitation. The attributable fraction and numbers of extreme precipitation on AMI hospitalizations were 0.68% (95% CI: 0.20%, 1.12%) and 854 (95% CI: 244, 1,395), respectively. Conclusion: Extreme precipitation is correlated with a higher risk of AMI hospitalizations. The elderly (≥65 years) and females are more susceptible to AMI triggered by extreme precipitation.


Asunto(s)
Hospitalización , Infarto del Miocardio , Anciano , Beijing/epidemiología , China/epidemiología , Femenino , Humanos , Infarto del Miocardio/epidemiología , Tiempo (Meteorología)
8.
Brain Sci ; 12(10)2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36291351

RESUMEN

Sound-induced flash illusion (SiFI) is typical auditory dominance phenomenon in multisensory illusion. Although a number of studies have explored the SiFI in terms of age-related effects, the reasons for the enhanced SiFI in older adults are still controversial. In the present study, older and younger adults with equal visual discrimination were selected to explore age differences in SiFI effects, and to explore the neural indicators by resting-state functional magnetic resonance imaging (rs-fMRI) signals. A correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and the SiFI. The results showed that both younger and older adults experienced significant fission and fusion illusions, and fission illusions of older adults were greater than that of younger adults. In addition, our results showed ReHo values of the left middle frontal gyrus (MFG), the right inferior frontal gyrus (IFG) and right superior frontal gyrus (SFG) were significantly positively correlated with the SiFI in older adults. More importantly, the comparison between older and younger adults showed that ReHo values of the right superior temporal gyrus (STG) decreased in older adults, and this was independent of the SiFI. The results indicated that when there was no difference in unisensory ability, the enhancement of multisensory illusion in older adults may not always be explained by compensation mechanisms.

9.
Perception ; 51(6): 388-402, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35435070

RESUMEN

Pairing a single visual stimulus with multiple auditory stimuli will lead to the illusory perception of multiple visual stimuli, which is known as sound-induced flash illusion (SIFI). The present study adopted the classic SIFI paradigm to investigate whether value-associated tasks could affect the SIFI. By adjusting the sequence of reward and nonreward conditions, we also examined the effect of reward history on SIFI. The results showed that the fission illusion was reduced when associated with momentary reward, demonstrating significantly higher accuracy and discriminability than the nonreward condition. However, the fusion illusion was not affected by the momentary reward, and the explanation was that the fusion illusion was not as stable as the fission illusion and disappeared across different trials and conditions. Moreover, the robustness of reward history in the present study was not as strong as previous studies have suggested, indicating that the effect of sound on the perceptual representation of visual stimuli is strong and robust to reward history. These findings demonstrated that the reward could reduce the SIFI and broaden the existing dichotomy of SIFI. New evidence for the operation of value-driven attention mechanisms is also provided, suggesting that the underlying value-driven attention operates across multiple sensory systems.


Asunto(s)
Ilusiones , Estimulación Acústica/métodos , Percepción Auditiva , Humanos , Estimulación Luminosa/métodos , Recompensa , Percepción Visual
10.
Respir Res ; 23(1): 38, 2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35189885

RESUMEN

BACKGROUND: Studies on the associations between ambient temperature and asthma hospitalizations are limited, and the results are controversial. We aimed to assess the short-term effects of ambient temperature on the risk of asthma hospitalizations and quantify the hospitalization burdens of asthma attributable to non-optimal temperature in adults in Beijing, China. METHODS: We collected daily asthma hospitalizations, meteorological factors and air quality data in Beijing from 2012 to 2015. We applied a time-stratified case-crossover design and fitted a distributed lag non-linear model with a conditional quasi-Poisson regression to explore the association between ambient temperature and adult asthma hospitalizations. The effect modifications of these associations by gender and age were assessed by stratified analyses. We also computed the attributable fractions and numbers with 95% empirical confidence intervals (eCI) of asthma hospitalizations due to extreme and moderate temperatures. RESULTS: From 2012 to 2015, we identified a total of 18,500 hospitalizations for asthma among adult residents in Beijing, China. Compared with the optimal temperature (22 °C), the cumulative relative risk (CRR) over lag 0-30 days was 2.32 with a 95% confidence interval (CI) of 1.57-3.42 for extreme cold corresponding to the 2.5th percentile (- 6.5 °C) of temperature distribution and 2.04 (95% CI 1.52-2.74) for extreme heat corresponding to the 97.5th percentile (29 °C) of temperature distribution. 29.1% (95% eCI 17.5-38.0%) of adult asthma hospitalizations was attributable to non-optimum temperatures. Moderate cold temperatures yielded most of the burdens, with an attributable fraction of 20.3% (95% eCI 9.1-28.7%). The temperature-related risks of asthma hospitalizations were more prominent in females and younger people (19-64 years old). CONCLUSIONS: There was a U-shaped association between ambient temperature and the risk of adult asthma hospitalizations in Beijing, China. Females and younger patients were more vulnerable to the effects of non-optimum temperatures. Most of the burden was attributable to moderate cold. Our findings may uncover the potential impact of climate changes on asthma exacerbations.


Asunto(s)
Asma/terapia , Hospitalización/estadística & datos numéricos , Medición de Riesgo/métodos , Temperatura , Adulto , Asma/epidemiología , Beijing/epidemiología , Estudios Cruzados , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
11.
Bioresour Technol ; 347: 126721, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35051568

RESUMEN

Wheat straw was pretreated using ball milling (BM) promoted by solid particles (NaOH, NaCl, citric acid). NaOH showed the best synergistic interaction effect, due to the breakage of ß-1,4-glycosidic bonds among cellulose molecules by the alkali solid particles induced by BM. NaOH-BM pretreatment decreased the straw crystallinity from 46% to 21.4% and its average particle size from 398.3 to 50.6 µm in 1 h. After 4 h milling, the reducing-end concentration of cellulose increased by 3.8 times from 12.5 to 60.2 µM, with glucose yield increased by 2.1 times from 26.6% to 82.4% for 72 h enzymatic hydrolysis at cellulase loading of 15 FPU/g dry substrate. The pretreatment washing liquor was recycled for the re-treatment of partially pretreated biomass at 121 °C for 30 min, resulting in 99.4% glucose yield by enzymatic hydrolysis. BM assisted with alkali particles was an effective approach for improving biomass enzymatic saccharification.


Asunto(s)
Celulasa , Triticum , Biomasa , Celulosa , Hidrólisis
12.
Int J Hyg Environ Health ; 238: 113839, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34507107

RESUMEN

BACKGROUND: There is a paucity of studies investigating extreme cold events and asthma exacerbations. This study examined whether an association exists between cold spells and daily hospital admissions for asthma in Beijing, China from 2012 to 2016. METHODS: Daily hospital admissions for asthma, meteorological variables and air quality data were collected during 2012-2016 in Beijing. A cold spell was defined as a period of at least two consecutive days with the daily mean temperature below or at the 5th percentile (-7 °C) in cold seasons (November to March) during the study period. We applied a time-series design using quasi-Poisson regression combined with a distributed lag model to estimate the risk of asthma hospital admissions associated with cold spells. Stratified analyses by gender and age groups were conducted to identify the potential susceptible subpopulations to cold spells. We also explored the effect modification by air quality by dividing the daily air quality index (AQI) into two levels (high and low) based on the median value. RESULTS: Cold spells increased the risk of asthma hospital admissions, with the maximum cumulative relative risk (CRR) over three weeks (Lag0-21) in the total population. The highest single-day relative risk (RR) was found on the days of cold spells (Lag0) with the RR = 1.059 (95% CI: 1.008-1.113), and the CRR at Lag0-21 was 1.333 (95% CI: 1.049-1.693). Across different gender and age groups, younger people (<65 years) were more sensitive to cold spells. No significant effect modification by AQI was detected. CONCLUSION: Short-term exposure to cold spells is associated with an increased risk of hospital admissions for asthma in Beijing. During the cold spells, younger people aged <65 years were at particular risk for asthma exacerbations. Our results suggest that extreme cold events have a significant impact on asthma.


Asunto(s)
Contaminación del Aire , Asma , Anciano , Contaminación del Aire/análisis , Asma/epidemiología , Beijing/epidemiología , China/epidemiología , Frío , Hospitales , Humanos
13.
Front Cell Neurosci ; 15: 621252, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34122011

RESUMEN

Animal pose estimation tools based on deep learning have greatly improved animal behaviour quantification. These tools perform pose estimation on individual video frames, but do not account for variability of animal body shape in their prediction and evaluation. Here, we introduce a novel multi-frame animal pose estimation framework, referred to as OptiFlex. This framework integrates a flexible base model (i.e., FlexibleBaseline), which accounts for variability in animal body shape, with an OpticalFlow model that incorporates temporal context from nearby video frames. Pose estimation can be optimised using multi-view information to leverage all four dimensions (3D space and time). We evaluate FlexibleBaseline using datasets of four different lab animal species (mouse, fruit fly, zebrafish, and monkey) and introduce an intuitive evaluation metric-adjusted percentage of correct key points (aPCK). Our analyses show that OptiFlex provides prediction accuracy that outperforms current deep learning based tools, highlighting its potential for studying a wide range of behaviours across different animal species.

14.
Clin Cancer Res ; 27(18): 5038-5048, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-33419780

RESUMEN

PURPOSE: Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories. EXPERIMENTAL DESIGN: To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH. RESULTS: The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data. CONCLUSIONS: This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.


Asunto(s)
Biomarcadores de Tumor/inmunología , Inmunoterapia , Monitorización Inmunológica , Neoplasias/inmunología , Neoplasias/terapia , Humanos
15.
BMJ Open ; 11(1): e039745, 2021 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-33408200

RESUMEN

OBJECTIVES: Our work aimed at exploring the relationship between cold spells and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalisations in Beijing, China, and assessing the moderating effects of the intensities and the durations of cold spells, as well as identifying the vulnerable. DESIGN: A time-series study. SETTING: We obtained time-series data of AECOPD hospitalisations, meteorological variables and air quality index in Beijing, China during 2012-2016. PARTICIPANTS: All AECOPD hospitalisations among permanent residents in Beijing, China during the cold seasons (November-March) of 2012-2016 were included (n=84 571). PRIMARY AND SECONDARY OUTCOME MEASURES: A quasi-Poisson regression with a distributed lag model was fitted to investigate the short-term effects of cold spells on AECOPD hospitalisations by comparing the counts of AECOPD admissions during cold spell days with those during non-cold spell days. RESULTS: Cold spells under different definitions were associated with increased risk of AECOPD hospitalisations, with the maximum cumulative relative risk (CRR) over 3 weeks (lag0-21). The cumulative effects at lag0-21 increased with the intensities and the durations of cold spells. Under the optimal definition, the most significant single-day relative risk (RR) was found on the days of cold spells (lag0) with an RR of 1.042 (95% CI 1.013 to 1.072), and the CRR at lag0-21 was 1.394 (95% CI 1.193 to 1.630). The elderly (aged ≥65) were more vulnerable to the effects of cold spells on AECOPD hospitalisations. CONCLUSION: Cold spells are associated with increased AECOPD hospitalisations in Beijing, with the cumulative effects increased with intensities and durations. The elderly are at particular risk of AECOPD hospitalisations triggered by cold spells.


Asunto(s)
Contaminación del Aire , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Beijing/epidemiología , China/epidemiología , Frío , Hospitalización , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
16.
Front Public Health ; 9: 798746, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34976938

RESUMEN

Background: Previous studies suggested that exposure to air pollution could increase risk of asthma attacks in children. The aim of this study is to investigate the short-term effects of exposure to ambient air pollution on asthma hospital admissions in children in Beijing, a city with serious air pollution and high-quality medical care at the same time. Methods: We collected hospital admission data of asthma patients aged ≤ 18 years old from 56 hospitals from 2013 to 2016 in Beijing, China. Time-stratified case-crossover design and conditional Poisson regression were applied to explore the association between risk of asthma admission in children and the daily concentration of six air pollutants [particulate matter ≤ 2.5 µm (PM2.5), particulate matter ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)], adjusting for meteorological factors and other pollutants. Additionally, stratified analyses were performed by age, gender, and season. Results: In the single-pollutant models, higher levels of PM2.5, SO2, and NO2 were significantly associated with increased risk of hospital admission for asthma in children. The strongest effect was observed in NO2 at lag06 (RR = 1.25, 95%CI: 1.06-1.48), followed by SO2 at lag05 (RR = 1.17, 95%CI: 1.05-1.31). The robustness of effects of SO2 and NO2 were shown in two-pollutant models. Stratified analyses further indicated that pre-school children (aged ≤ 6 years) were more susceptible to SO2. The effects of SO2 were stronger in the cold season, while the effects of NO2 were stronger in the warm season. No significant sex-specific differences were observed. Conclusions: These results suggested that high levels of air pollution had an adverse effect on childhood asthma, even in a region with high-quality healthcare. Therefore, it will be significant to decrease hospital admissions for asthma in children by controlling air pollution emission and avoiding exposure to air pollution.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Asma , Adolescente , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Asma/inducido químicamente , Asma/epidemiología , Niño , Preescolar , China/epidemiología , Estudios Cruzados , Femenino , Hospitales , Humanos , Masculino , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Material Particulado/efectos adversos , Material Particulado/análisis
17.
Cancer Res ; 81(1): 158-173, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33158814

RESUMEN

Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies. The bispecific antibody induced superior cellular state changes in both T and natural killer (NK) cells. It uniquely induced NK cells to transition from inert to more active and cytotoxic phenotypes, implicating NK cells as a key missing component of the current ICB-induced immune response in HGSC. It also induced a subset of CD8 T cells to transition from naïve to more active and cytotoxic progenitor-exhausted phenotypes post-treatment, revealing the small, previously uncharacterized population of CD8 T cells responding to ICB in HGSC. These state changes were driven partially through bispecific antibody-induced downregulation of the bromodomain-containing protein BRD1. Small-molecule inhibition of BRD1 induced similar state changes in vitro and demonstrated efficacy in vivo, validating the co-culture results. Our results demonstrate that state changes in both NK and a subset of T cells may be critical in inducing an effective anti-tumor immune response and suggest that immune therapies able to induce such cellular state changes, such as BRD1 inhibitors, may have increased efficacy in HGSC. SIGNIFICANCE: This study indicates that increased efficacy of immune therapies in ovarian cancer is driven by state changes of NK and small subsets of CD8 T cells into active and cytotoxic states.


Asunto(s)
Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Cistadenocarcinoma Seroso/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Linfocitos T CD8-positivos/inmunología , Proliferación Celular , Cistadenocarcinoma Seroso/inmunología , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Células Asesinas Naturales/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Ratones , Clasificación del Tumor , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Front Psychol ; 11: 216, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32153456

RESUMEN

The sound-induced flash illusion (SiFI) is a classical auditory-dominated multisensory integration phenomenon in which the observer misperceives the number of visual flashes due to the simultaneous presentation of a different number of auditory beeps. Although the SiFI has been documented to correlate with perceptual sensitivity, to date there is no consensus as to how it corresponds to sensitivity with aging. The present study was based on the SiFI paradigm (Shams et al., 2000), adding repeated auditory stimuli prior to the appearance of audiovisual stimuli to investigate the effects of repetition suppression (RS) on the SiFI with aging. The repeated auditory stimuli consisted of one or two of the same auditory stimuli presented twice in succession, which were then followed by the audiovisual stimuli. By comparing the illusions in old and young adults, we aimed to explore the influence of aging on the RS of auditory stimuli on the SiFI. The results showed that both age groups showed SiFI effects, however, the RS performance of the two age groups had different effects on the fusion and fission illusions. The illusion effect in old adults was weaker than in young adults. Specifically, RS only affected fission illusions in the old adults but both fission and fusion illusions in young adults. Thus, the present study indicated that the decreased perceptual sensitivity based on auditory RS could weaken the SiFI effect in multisensory integration and that old adults are more susceptible to RS, showing that old adults perceived the SiFI effect weakly under auditory RS.

19.
Artículo en Inglés | MEDLINE | ID: mdl-32099346

RESUMEN

Purpose: To evaluate the associations between acute exacerbations of chronic obstructive pulmonary disease (AECOPD) hospitalizations and daily mean temperature (Tmean) as well as daily apparent temperature (AT), and to explore the practical values of these two indices in policymaking and patient education. Methods: Daily AECOPD hospitalizations and Meteorological data in Beijing were obtained between 2013 and 2016. Distributed lag non-linear model was adopted to investigate the association between daily ambient temperature and AECOPD hospitalizations. The cumulative effects of cold/hot temperature were abstracted. For the extreme and moderate low-temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 1st and 10th percentiles of temperature in comparison with that at the 25th percentile of temperature. For the extreme and moderate high temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 99th and 90th percentiles of temperature in comparison with that at the 75th percentile of temperature. Results: During the study period, 143, 318 AECOPD hospitalizations were collected. A reverse J-shape relationship was found between temperature and AECOPD hospitalizations. When comparing the effect of Tmean, higher RRs were associated with increases in AT on AECOPD hospitalizations but a lower value of Akaike's Information Criterion for quasi-Poisson (Q-AIC). The RR of extremely low temperature of Tmean and AT were 1.55 (95% CI: 1.21,2.00) and 2.08 (95% CI: 1.44,3.01), respectively. Moderate low temperature also had an adverse impact on AECOPD hospitalizations. No associations were found between high temperature and AECOPD risk. We found the females and those aged <65 years to be more susceptible to temperature change. Conclusion: Lower temperature is associated with a higher risk for AECOPD hospitalizations. Ambient temperature is probably a better predictor in terms of quantifying risk than mean temperature when studying temperature impact on health.


Asunto(s)
Hospitalización , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estaciones del Año , Temperatura , Anciano , Beijing/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
20.
ACS Omega ; 4(20): 18487-18494, 2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31737806

RESUMEN

Alkali lignin is a component of the waste black liquor produced by the paper-making industry that is difficult to degrade. In recent years, the biological activities of lignin, such as free-radical scavenging and antioxidant capacity, have received increasing attention. Here, we prepared H3PW12O40/ZrO2 and used this catalyst together with the ionic liquid 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) as a double-effect catalyst for the degradation of alkali lignin. Single-factor and orthogonal tests showed that the best degradation conditions were as follows: reaction time, 2 h; reaction temperature, 100 °C; mass ratio of H3PW12O40/ZrO2 to lignin, 1:4; and substrate concentration, 2.5%. The phenolic hydroxyl group content of the lignin degradation product increased by 231.2% and the total hydroxyl group content increased by 337.1% when the double-effect catalyst was used rather than [BMIM]Cl alone. Analysis by gel permeation chromatography showed that both the weight-average molecular weight and the number-average molecular weight of the product were reduced and that the lignin was degraded into small-molecular-weight compounds by the macromolecule. The product after the catalytic degradation of lignin showed a markedly increased antioxidant capacity, which was similar to that of the commercial antioxidant, 2,6-ditert-butyl-4-methylphenol. The study opens up a new direction for the better utilization of lignin.

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