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1.
Sci Total Environ ; 785: 147236, 2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33932661

RESUMEN

Haze has become an important factor to harm people's health. In the face of the harm of haze, people express risk perception behavior through publishing online comments on haze news. To a certain extent, online comments affect the government's decision to deal with haze. However, most of the previous efforts only focused on several cities from a micro perspective whereas the existing research lacks to explore the regional differences of risk perception behavior of the whole country from a macro perspective. The macro perspective of research can help policymakers to formulate strategies of haze control according to local conditions. Therefore, it is important to understand the risk perception behavior of publishing online comments and haze from the macro perspective. In this study, we use quantitative methods to study the spatial-temporal characteristics of online comments and PM2.5 in 334 cities in China from 2014 to 2018. From the spatial perspective, the spatial characteristics of online comments are quite different from those of PM2.5 at the city level. It can be seen that the spatial mismatch can affect the government's strategy of haze control according to local conditions. From the perspective of influencing factors, we find that the risk perception behavior of publishing online comments conforms to the theory of environmental risk perception. Firstly, the local social development level is the largest driving force accelerating risk perception behavior. Secondly, information channel also has significantly positive effect on public risk perception behavior. Finally, the harmful degree of haze has the least positive effect on people's risk perception behavior. This gives us enlightenment. The number of online comments does not reflect the harmful degree of haze in different regions. We suggest that online comments should not be the main reference factor for policymakers to make strategies.

2.
Pain ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33945242

RESUMEN

Human fMRI and behavioral studies have established the roles of cortical areas along the sylvian fissure in sensing subjective pain. Yet, little is known about how sensory aspects of painful information are represented and processed by neurons in these regions and how their electrophysiological activities are related to fMRI signals. The current study aims to partially address this critical knowledge gap by performing fMRI guided microelectrode mapping and recording studies in the homologous region of the parietal operculum in squirrel monkeys under light anesthesia. In each animal studied (n=8), we detected mesoscale mini networks for heat nociception in cortical regions around the lateral sulcus. Within the network, we discovered a ∼ 1.5x1.5 mm sized cortical patch that solely contained heat nociceptive neurons that aligned with the heat fMRI activation locus. These neurons responded slowly to thermal (heat and cold) nociceptive stimuli exclusively, continued firing for several seconds after the succession of stimulation, and exhibited multidigit receptive fields and high spontaneous firing rates. Similar to the fMRI responses, increasing temperatures in the nociceptive range led to a non-linear increase in firing rates. The finding of a clustering of heat nociceptive neurons provides novel insights into the unique functional organization of thermal nociception in the S2 subregion of the primate brain. With fMRI, it supports the existence of a modality preferred heat nociceptive patch that is spatially separated and intermingled with touch patches containing neurons with comparable receptive fields, and the presence of functionally distinct mini networks in primate opercular cortex.

3.
Mol Med Rep ; 24(1)2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33955501

RESUMEN

The aim of the present study was to investigate the effects of human epididymis protein 4 (HE4) on drug resistance and its underlying mechanisms. The associations among proteins were detected by immunoprecipitation and immunofluorescence assays. Then, stably transfected cell lines CAOV3­HE4­L and CAOV3­A2­L expressing HE4 short hairpin (sh)RNAs and ANXA2 shRNAs, respectively, were constructed. MTT assay, immunocytochemistry, western blotting, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and flow cytometry were employed to examine drug sensitivity, as well as the expression and activity of P­glycoprotein (P­gp). HE4 and P­gp in epithelial ovarian cancer tissues were assessed via immunohistochemistry. MicroRNAs that targeted the P­gp gene, ABCB1, were predicted using bioinformatics methods, and their expression was evaluated by RT­qPCR. The common signaling pathways shared by HE4, ANXA2 and P­gp were selected by Gene Set Enrichment Analysis (GSEA). The interaction of HE4, ANXA2 and P­gp were confirmed. P­gp expression was positively associated with HE4 and ANXA2 expression, respectively. Moreover, it was observed that there was no significant rescue of P­gp expression in CAOV3­A2­L cells following the administration of active HE4 protein. In addition, the expression of HE4 and P­gp in ovarian cancer tissues of drug­resistant patients were higher compared with that of the drug­sensitive group (P<0.05). Furthermore, the results revealed that hsa­miR­129­5p was significantly increased accompanied by decreased HE4 or ANXA2 expression and P­gp expression in CAOV3­HE4­L and CAOV3­A2­L cells. GSEA analyses disclosed that HE4, ANXA2 and P­gp genes were commonly enriched in the signaling pathway involved in regulating the actin cytoskeleton. These results indicated that HE4 promotes P­gp­mediated drug resistance in ovarian cancer cells through the interactions with ANXA2, and the underlying mechanism may be associated with decreased expression of hsa­miR­129­5p and dysregulation of the actin cytoskeleton signaling pathway.

4.
Talanta ; 231: 122414, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-33965054

RESUMEN

Biosensors based on various spectroscopic techniques discriminate the target microRNA (miRNA) from non-target ones with single nucleotide polymorphisms (SNPs) according to the differences in signal intensities which can be caused by other factors besides SNPs. As a result, they are liable to produce false positive results. Herein, we report an attempt to develop a false-positive resistance, sensitive and reliable mass spectrometric platform for miRNA detection. In the proposed platform, the qualitative and quantitative information of the target miRNA was obtained through analyzing mass spectral responses of the multiply charged ions of the residual fragments of the probe DNA produced during exonuclease III assisted signal amplification reaction using an advanced data analysis method. The proposed platform could achieve sensitive and accurate quantitative results for the target miRNA (e.g., miRNA-141) in complex medium with a detection limit of about 1 pM, and unambiguously identify non-target miRNAs with SNPs based on the length distribution patterns of residual fragments of probe DNA. The findings obtained in this study might open an avenue for the design of new miRNA detection methods based on mass spectrometry in combination with various nuclease assisted signal amplification strategies.

5.
Cell Biol Int ; 2021 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-33969575

RESUMEN

Sorafenib was the first systemic therapy approved by the food and drug administration (FDA) to treat advanced hepatocellular carcinoma (HCC). However, Sorafenib therapy is frequently accompanied by drug resistance. We aimed to explore the mechanisms of Sorafenib resistance and provide feasible solutions to increase the response to Sorafenib in patients with advanced HCC. The expression profile of discoidin domain receptor 2 (DDR2) in HCC tissues and cells was detected using quantitative real-time PCR (qPCR) and western blotting assays. The effects of DDR2 on Sorafenib resistance were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, TdT-mediated dUTP nick end labeling (TUNEL), and flow cytometry assays. The effect of DDR2 on the nuclear factor kappa B (NF-κB) signaling pathway was evaluated by luciferase reporter, immunofluorescence, qPCR and flow cytometry assays. We demonstrated that DDR2 expression was dramatically upregulated in Sorafenib-resistant HCC tissues relative to sensitive tissues. Downregulation of DDR2 sensitized HCC cell lines to Sorafenib cytotoxicity. Further analysis showed that DDR2 could increase the nuclear location of REL proto-oncogene, a NF-κB subunit, to mediate NF-κB signaling. Blocking NF-κB signaling using the NF-κB signaling inhibitor, Bardoxolone Methyl, increased the response of HCC cells to Sorafenib. Further analysis showed that DNA amplification of DDR2 is an important mechanism leading to DDR2 overexpression in HCC. Our results demonstrated that DDR2 is a potential therapeutic target in patients with HCC, and targeting DDR2 represents a promising approach to increase Sorafenib sensitivity in patients with HCC. This article is protected by copyright. All rights reserved.

6.
PLoS One ; 16(5): e0250602, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33939733

RESUMEN

OBJECTIVE: We aimed to systematically identify the possible risk factors responsible for severe cases. METHODS: We searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients' disease. We analyzed the potential associations between clinical characteristics and severe cases. RESULTS: We identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34-2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33-1.71), obesity (OR = 1.89, 95% CI: 1.44-2.46), history of smoking (OR = 1.40, 95% CI:1.06-1.85), hypertension (OR = 2.42, 95% CI: 2.03-2.88), diabetes (OR = 2.40, 95% CI: 1.98-2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22-3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63-5.41), cerebrovascular disease (OR = 2.47, 95% CI: 1.54-3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89-4.38), malignancy (OR = 2.60, 95% CI: 2.00-3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06-2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99-78.41), shock (OR = 21.50, 95% CI: 10.49-44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34-18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions. CONCLUSION: Patients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

7.
J Invertebr Pathol ; : 107593, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33961881

RESUMEN

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular and non-structural glycoprotein. In shrimp, a significant function of SPARC in WSSV infection remains unclear. In this study, the full-length cDNA sequence of a secreted protein acidic and rich in cysteine -like was cloned from shrimp Litopenaeus vannamei (named as LvSPARC-L). LvSPARC-L contained an open reading frame of 1002 bp, encoding 333 amino acids. Bioinformatics analysis showed that LvSPARC-L contained a SPARC Ca2+-binding region in the C-terminus, a Kazal-type serine protease inhibitor domain and a BUD22 domain. Tissue distribution assay indicated that LvSPARC-L generally expressed in all tissues selected with a higher expression in hemocyte, stomach and pleoplod. In hepatopancreas and intestine, the relative expression of LvSPARC-L was significantly up-regulated following the WSSV challenge. Besides, the relative expression of viral immediately early gene IE1 and a late gene VP28 was significantly increased in the LvSPARCL-silenced shrimp. Furthermore, the relative expression of LvP53 and LvCaspase3 was extremely decreased in the stomach of dsLvSPARC-L treated shrimp, while that of LvP38 was not affected significantly. All data together suggest that LvSPARC-L might play an antiviral role by regulating apoptosis.

9.
Am J Clin Nutr ; 2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-33963745

RESUMEN

BACKGROUND: Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas. OBJECTIVES: We aimed to evaluate whether dietary patterns are associated with NPC risk. METHODS: We studied 2554 newly diagnosed NPC patients aged 20-74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk. RESULTS: Compared with the lowest quartile, individuals in the highest quartile of the "plant-based factor" in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the "animal-based factor" had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend < 0.0001). Similar but weaker associations were found in adolescence. High intakes of the "preserved-food factor" were associated with increased NPC risk in both periods, although stronger associations were found in adolescence. Results from joint analysis and sensitivity analyses indicated that dietary factors in adulthood might be more stable and robust predictors of NPC risk than those in adolescence. CONCLUSIONS: Our results deliver compelling evidence that plant- and animal-based dietary factors are associated with NPC risk, and provide more insights on the associations of diets and cancer risk that may assist healthy diet recommendations.

10.
Tree Physiol ; 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33960381

RESUMEN

Phytoremediation technology can help achieve moderate cost and considerable effect, with respect to the remediation of heavy metal pollution in soil and water. Many previous studies have suggested the role of N in the alleviation of effects of heavy metal on plants. Herein, we sought to determine the molecular mechanisms by which additional N supplementation mitigates Cd toxicity in poplars using a combination of physiological, transcriptomic, and phosphoproteomic analyses. The application of N can alleviate the toxicity of Cd to Populus by reducing chlorophyll degradation, maintaining the stability of ions inside and outside the cell membrane, and increasing the soluble sugar content. Plant samples from the control (CK), Cd stress, and Cd_N treatments were used for an integrated analysis of the transcriptome, as well as for phosphoproteomics analysis. Moreover, 1,314 differentially expressed genes (DEGs) and 119 differentially expressed kinase genes were discovered. Application of additional N under Cd stress promoted the phosphorylation process. Furthermore, 51 significantly enriched phosphorylated protein sites and 23 differentially expressed kinases were identified using phosphoproteomic and proteomic analyses. Importantly, transcriptomic and phosphoproteomic analyses jointly determined that the application of N could activate corresponding gene expression [UDP-glucose-dehydrogenase (UGD), GAUT, PME, pectin lyase, UDP-glucose-pyrophosphorylase 2 (UGP2), sucrose phosphate synthase (SPS), SUS, and SPP2] and protein phosphorylation (UGP2 and SPS) in the sugar and starch synthesis pathways, which promoted the synthesis of sucrose and soluble sugar and subsequently alleviated the damage caused by Cd.

11.
Front Neural Circuits ; 15: 643230, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33935658

RESUMEN

The CA1, an important subregion of the hippocampus, is anatomically and functionally heterogeneous in the dorsal and ventral hippocampus. Here, to dissect the distinctions between the dorsal (dCA1) and ventral CA1 (vCA1) in anatomical connections, we systematically analyzed the direct inputs to dCA1 and vCA1 projection neurons (PNs) with the rabies virus-mediated retrograde trans-monosynaptic tracing system in Thy1-Cre mice. Our mapping results revealed that the input proportions and distributions of dCA1 and vCA1 PNs varied significantly. Inside the hippocampal region, dCA1 and vCA1 PNs shared the same upstream brain regions, but with distinctive distribution patterns along the rostrocaudal axis. The intrahippocampal inputs to the dCA1 and vCA1 exhibited opposite trends, decreasing and increasing gradually along the dorsoventral axis, respectively. For extrahippocampal inputs, dCA1 and vCA1 shared some monosynaptic projections from certain regions such as pallidum, striatum, hypothalamus, and thalamus. However, vCA1, not dCA1, received innervations from the subregions of olfactory areas and amygdala nuclei. Characterization of the direct input networks of dCA1 and vCA1 PNs may provide a structural basis to understand the differential functions of dCA1 and vCA1.

12.
Trop Anim Health Prod ; 53(2): 299, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33939008

RESUMEN

Bovine viral diarrhea virus (BVDV) and peste des petits ruminants virus (PPRV) are two important pathogens associated with a variety of disease syndromes that result in substantial financial losses in animal husbandry. This study was performed to assess the seroprevalence of antibodies to BVDV and PPRV among alpacas raised in Shanxi Province of northern China. Serum samples were obtained from 246 alpacas in Taiyuan (n=182), Xinzhou (n=31), and Jinzhong cities (n=33) of Shanxi Province, and serological testing was carried out using the competitive enzyme-linked immunosorbent assay. Overall seroprevalence to BVDV was 3.25% (95% CI 1.03-5.47), and seropositive alpacas were found only in Taiyuan City. The overall PPRV seroprevalence in alpacas was 28.86% (95% CI 23.20-34.52). While no PPRV-seropositive alpacas were found in Xinzhou City, the seroprevalence of PPRV was 90.91% (95% CI 81.10-100.72) in Jinzhong City and 22.53% (95% CI 16.46-28.60) in Taiyuan City, respectively, which showed a statistically significant difference. To our knowledge, the present work is the first report on seroprevalence of BVDV and PPRV in alpacas in China, which provides baseline information for the control of infection.

13.
J Neuroimmunol ; 355: 577571, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33866281

RESUMEN

The study aims to identify clinical factors affecting tacrolimus blood trough concentration (C0) in myasthenia gravis (MG) patients and to optimize the initial dose of tacrolimus in MG treatment. A total of 103 MG patients participated in this study, and their clinical factors, medication regimens, C0 values and CYP3A5*3 polymorphisms were collected in detail. We used a linear mixed model to analyze the effect of multiple factors on the dosage-weighted C0 (C0:D) and performed subgroup analyses to investigate the consistency of correlations between influencing factors and the C0:D ratios. Among all factors, CYP3A5*3 polymorphism and age showed a strong positive correlation with C0:D ratios. The C0:D ratios (ng/ml·mg-1) were higher for CYP3A5*3/*3 than for CYP3A5*1 (mean difference: 1.038, 95% confidence interval [CI]: 0.820-1.256, P-value <0.001), and for age in the range of 45-64 and ≥ 65 years than for age < 45 years (mean difference [95% CI] and P-value: 0.531[0.257-0.805] and P-value <0.001, 0.703 [0.377-1.029] and P-value <0.001, respectively). The C0:D ratios were not related to corticosteroid dosage, body weight, sex, hematocrit or the concomitant use of calcium channel blockers. The consistencies of the correlations between C0:D ratios and CYP3A5*3 polymorphism or age were confirmed by subgroup analyses. Thus, CYP3A5*3 polymorphism and age should be considered in optimizing the initial dose of tacrolimus for MG treatment.

14.
Infect Dis Poverty ; 10(1): 56, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33902695

RESUMEN

BACKGROUND: As one of the non-pharmacological interventions to control the transmission of COVID-19, determining the quarantine duration is mainly based on the accurate estimates of the incubation period. However, patients with coarse information of the exposure date, as well as infections other than the symptomatic, were not taken into account in previously published studies. Thus, by using the statistical method dealing with the interval-censored data, we assessed the quarantine duration for both common and uncommon infections. The latter type includes the presymptomatic, the asymptomatic and the recurrent test positive patients. METHODS: As of 10 December 2020, information on cases have been collected from the English and Chinese databases, including Pubmed, Google scholar, CNKI (China National Knowledge Infrastructure) and Wanfang. Official websites and medias were also searched as data sources. All data were transformed into doubly interval-censored and the accelerated failure time model was applied. By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients, we obtain the large percentiles for determining and suggesting the quarantine policies. For symptomatic and presymptomatic COVID-19 patients, the incubation time is the duration from exposure to symptom onset. For the asymptomatic, we substitute the date of first positive result of nucleic acid testing for that of symptom onset. Furthermore, the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients. RESULTS: A total of 1920 laboratory confirmed COVID-19 cases were included. Among all uncommon infections, 34.1% (n = 55) of them developed symptoms or were identified beyond fourteen days. Based on all collected cases, the 95th and 99th percentiles were estimated to be 16.2 days (95% CI 15.5-17.0) and 22.9 days (21.7‒24.3) respectively. Besides, we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days (14.4‒15.7) and 21.1 days (20.0‒22.2). CONCLUSIONS: There are a certain number of infected people who require longer quarantine duration. Our findings well support the current practice of the extended active monitoring. To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine, properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.


Asunto(s)
/prevención & control , Cuarentena/métodos , /fisiología , Adolescente , Adulto , Anciano , Enfermedades Asintomáticas/epidemiología , Infecciones Asintomáticas/epidemiología , Portador Sano/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Periodo de Incubación de Enfermedades Infecciosas , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Factores de Tiempo , Adulto Joven
15.
Molecules ; 26(9)2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33923350

RESUMEN

In this paper, ultrasonic cellulase extraction (UCE) was applied to extract polyphenols from passion fruit. The extraction conditions for total phenol content (TPC) and antioxidant activity were optimized using response surface methodology (RSM) coupled with a Box-Behnken design (BBD). The results showed that the liquid-to-solid ratio (X2) was the most significant single factor and had a positive effect on all responses. The ANOVA analysis indicated quadratic models fitted well as TPC with R2 = 0.903, DPPH scavenging activity with R2 = 0.979, and ABTS scavenging activity with R2 = 0.981. The optimal extraction parameters of passion fruit were as follows: pH value of 5 at 30 °C for extraction temperature, 50:1 (w/v) liquid-to-solid ratio with extraction time for 47 min, the experimental values were found matched with those predicted. Infrared spectroscopy suggested that the extract contained the structure of polyphenols. Furthermore, three main polyphenols were identified and quantified by HPLC. The results showed the content of phenolic compounds and antioxidant activity of the optimized UCE were 1.5~2 times higher than that determined by the single extraction method and the Soxhlet extraction method, which indicates UCE is a competitive and effective extraction technique for natural passion fruit polyphenols.

16.
Cell Biochem Funct ; 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33929054

RESUMEN

Autophagy is an evolutionarily conserved cellular process, in which damaged organelles and proteins are engulfed in autophagic vesicles and subsequently fuse with lysosomes for degradation. Autophagy is widely involved in different physiologic or pathologic processes in human. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism to maintain pulp homeostasis and structural integrity of the dentin-pulp complex. Autophagy is activated during stresses and is involved in the pathogenesis of pulpitis and periapical infection. Recent discoveries have also provided intriguing insights into the roles of autophagy in tooth development, pulp aging and stress adaptation. In this review, we provide an update on the multifaceted functions of autophagy in physiology and pathophysiology of tooth. We also discuss the therapeutic implications of autophagy modulation in diseases and the regeneration of dentin-pulp complex.

17.
Respir Res ; 22(1): 122, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33902571

RESUMEN

BACKGROUND: Asthma has been associated with impaired interferon response. Multiple cell types have been implicated in such response impairment and may be responsible for asthma immunopathology. However, existing models to study the immune response in asthma are limited by bulk profiling of cells. Our objective was to Characterize a model of peripheral blood mononuclear cells (PBMCs) of patients with severe asthma (SA) and its response to the TLR3 agonist Poly I:C using two single-cell methods. METHODS: Two complementary single-cell methods, DropSeq for single-cell RNA sequencing (scRNA-Seq) and mass cytometry (CyTOF), were used to profile PBMCs of SA patients and healthy controls (HC). Poly I:C-stimulated and unstimulated cells were analyzed in this study. RESULTS: PBMCs (n = 9414) from five SA (n = 6099) and three HC (n = 3315) were profiled using scRNA-Seq. Six main cell subsets, namely CD4 + T cells, CD8 + T cells, natural killer (NK) cells, B cells, dendritic cells (DCs), and monocytes, were identified. CD4 + T cells were the main cell type in SA and demonstrated a pro-inflammatory profile characterized by increased JAK1 expression. Following Poly I:C stimulation, PBMCs from SA had a robust induction of interferon pathways compared with HC. CyTOF profiling of Poly I:C stimulated and unstimulated PBMCs (n = 160,000) from the same individuals (SA = 5; HC = 3) demonstrated higher CD8 + and CD8 + effector T cells in SA at baseline, followed by a decrease of CD8 + effector T cells after poly I:C stimulation. CONCLUSIONS: Single-cell profiling of an in vitro model using PBMCs in patients with SA identified activation of pro-inflammatory pathways at baseline and strong response to Poly I:C, as well as quantitative changes in CD8 + effector cells. Thus, transcriptomic and cell quantitative changes are associated with immune cell heterogeneity in this model to evaluate interferon responses in severe asthma.

18.
Brain Tumor Pathol ; 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33903981

RESUMEN

Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients.

19.
Aliment Pharmacol Ther ; 53(11): 1216-1225, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33857339

RESUMEN

BACKGROUND: Menopausal hormone therapy (MHT) has been associated with various malignancies. AIMS: To investigate the association of various MHT regimens with the risk of colorectal cancer (CRC). METHODS: All MHT ever-users (n = 290 186) were included through the Swedish Prescribed Drug Registry, with a 1:3 group-level matching to non-users. Ever-users were defined as women who received ≥1 dispensed prescription of systemic MHT during 2005-2012 in Sweden. All CRC cases after drug initiation were extracted from the Swedish Cancer Registry. The association was assessed by multivariable conditional logistic and Cox regression models, presented as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) considering different regimens, duration and age at treatment initiation. RESULTS: Compared with non-users, MHT users had an overall reduced odds for colon (OR = 0.67, 95% CI 0.63-0.72) and rectal adenocarcinoma (OR = 0.66, 95% CI 0.60-0.73), especially among women aged 40-60 years. Current users of oestrogen-only preparations (E-MHT) showed a reduced odds (colon OR = 0.73, 95% CI 0.65-0.82; rectal OR = 0.76, 95% CI 0.64-0.90) compared to non-users, particularly with oestradiol and oestriol. Past E-MHT use showed stronger odds reductions (colon OR = 0.49, 95% CI 0.43-0.56; rectal OR = 0.36, 95% CI 0.28-0.45). Current use of oestrogen combined progestin therapy (EP-MHT) indicated a less prominent odds reduction (colon adenocarcinoma OR 0.62, 95% CI 0.54-0.72; rectal adenocarcinoma OR = 0.60, 95% CI 0.49-0.74) than past users. Tibolone showed an increased risk of left-sided colorectal adenocarcinoma. Oral and cutaneous MHT usage showed similar patterns. CONCLUSIONS: MHT use may decrease colorectal adenocarcinoma risk, for both E-MHT and EP-MHT, and especially in past users.

20.
Small ; : e2100439, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33891802

RESUMEN

Interfacial engineering and heterostructures designing are two efficient routes to improve photoelectric characteristics of a photodetector. Herein, a Ti3 C2 MXene/Si heterojunction photodetector with ultrahigh specific detectivity (2.03 × 1013 Jones) and remarkable responsivity (402 mA W-1 ) at zero external bias without decline as with increasing the light power is reported. This is achieved by chemically regrown interfacial SiOx layer and the control of Ti3 C2 MXene thickness to suppress the dark noise current and improve the photoresponse. The photodetector demonstrates a high light on/off ratio of over 106 , an outstanding peak external quantum efficiency (EQE) of 60.3%, while it maintains an ultralow dark current at 0 V bias. Moreover, the device holds high performance with EQE of over 55% even after encapsulated with silicone, trying to resolve the air stability issue of Ti3 C2 MXene. Such a photodetector with high detectivity, high responsivity, and self-powered capability is particularly applicable to detect weak light signal, which presents high potential for imaging, communication and sensing applications.

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