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1.
Food Chem ; 355: 129479, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33799258

RESUMO

Applications of cyanidin-3-O-glucoside (C3G) are limited due to the poor stabilities. In this work, we proposed using silk fibroin peptide (SFP) to bind with C3G and form nanocomposites (134.73 ± 4.51 nm) for stabilization. When interacted with C3G, the fluorescence of SFP contributed by tyrosine and phenylalanine amino acids was quenched, which was proved a static quenching with the ß-sheet structure of SFP unchanged. With the further exploration of the physicochemical stabilities of C3G in the nanocomposites, we demonstrated that the tolerance of C3G to the alkaline environment and the retention ratio of C3G in various concentrations of metallic ion Cu2+ were significantly improved. In addition, the heat resistance of C3G in SFP at 80 °C was also enhanced with up to an increase of 2.5 times for the average half-life of C3G. Our results shed light on SFP could enhance physicochemical stabilities of C3G with maintaining its antioxidant activity.

2.
Behav Brain Res ; : 113263, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33775776

RESUMO

Total sleep deprivation (TSD) causes a decline in almost all cognitive domains, especially working memory. However, we do not have a clear understanding of the degree working memory is impaired under prolonged TSD, nor do we know the underlying neurophysiological mechanism. In this study, we recorded EEG data from 64 subjects while they performed a working memory task during resting wakefulness, after 24 h TSD, and after 30 h TSD. ANOVA was used to verify performance differences between 24 h and 30 h TSD in working memory tasks: (1) reaction time and accuracy hit rates, (2) P200, N200, and P300 amplitude and latency in measurements of event-related potential, as well as (3) effective connectivity strength between brain areas associated with working memory. Compared to 24 h TSD, 30 h TSD significantly decreased accuracy hit rates and induced a larger N200 difference waveform. The effective connectivity analysis showed that 30 h TSD also decreased beta frequency in effective connection strength from the right insular lobe to the left anterior cingulate cortex (ACC). Effective connection from the left ventrolateral prefrontal cortex to the left dorsolateral prefrontal cortex increased in the match condition of the 2-back task. In conclusion, 30 h TSD had a greater negative impact on working memory than 24 h TSD. This impairment of working memory is associated with decreased strength in the effective connection from the right insula to the left ACC.

3.
J Nat Prod ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33721994

RESUMO

The discovery of efficient and specific HIV-latency-reversing agents is critical for HIV therapy. Here, we developed wikstroelide E, a daphnane diterpene from the buds of Wikstroemia chamaedaphne, as a potential HIV-latency-reversing agent that is 2500-fold more potent than the drug prostratin. Based on transcriptome analysis, the underlying mechanism was that wikstroelide E regulated the MAPK, PI3K-Akt, JAK-Stat, TNF, and NF-κB signaling pathways. We clearly demonstrated that wikstroelide E reversed latent HIV infection by activating PKC-NF-κB signals, serving as a proxy for verifying the transcriptome data. Strikingly, the Tat protein contributes to the robust activation of latent HIV in wikstroelide-E-treated cells, producing an unexpected latency-reversing effect against latent HIV. This study provides the basis for the potential development of wikstroelide E as an effective HIV-latency-reversing agent.

4.
Stroke Vasc Neurol ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737399

RESUMO

BACKGROUND: Haemorrhages of brainstem cavernous malformations (CMs) can lead to neurological deficits, the natural history of which is uncertain. The study aimed to evaluate the neurological outcomes of untreated brainstem CMs and to identify the adverse factors associated with worsened outcomes. METHODS: From 2009 to 2015, 698 patients (321 women) with brainstem CMs were entered into the prospective cohort after excluding patients lost to follow-up (n=43). All patients were registered, clinical data were collected and scheduled follow-up was performed. RESULTS: After a median follow-up of 60.9 months, prospective haemorrhages occurred in 167 patients (23.9%). The mean modified Rankin Scale scores at enrolment and at censoring time were 1.6 and 1.2. Neurological status was improved, unchanged and worsened in 334 (47.9%), 293 (42.0%) and 71 (10.2%) patients, respectively; 233 (33.4%) recovered to normal levels. Lesions crossing the axial midpoint (relative risk (RR) 2.325, p=0.003) and developmental venous anomaly (DVA) (RR 1.776, p=0.036) were independently significantly related to worsened outcomes. The percentage of worsened outcomes was 5.3% (18 of 337) in low-risk patients (neither DVA nor crossing the axial point) and increased to 26.0% (13 of 50) in high-risk patients (with both DVA and crossing the axial point). The percentage of worsened outcomes significantly increased as the number of prospective haemorrhages increased (from 1.5% (8 of 531, if 0 prospective ictus) to 37.5% (48 of 128, if 1 ictus) and 38.5% (15 of 39, if >1 ictus)). CONCLUSIONS: The neurological outcomes of untreated brainstem CMs were improved/unchanged in majority of patients (89.8%) with a fatality rate of 1.7% in our cohort, which seemed to be favourable. Radiological features significantly predicted worsened outcomes. Our results provide evidence for clinical consultation and individualised treatment. The referral bias of our cohort was underlined.

5.
Int Urol Nephrol ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675474

RESUMO

OBJECTIVE: The present study investigated the predictive value of albuminuria for contrast-induced nephropathy (CIN) non-recovery in patients undergoing percutaneous coronary intervention (PCI). METHODS: We retrospectively enrolled 550 consecutive patients inflicted with CIN after PCI and reassessing kidney function among 1 week-12 months between January 2012 and December 2018. Patients were stratified into three groups according to urine albumin: negative group (urine dipstick negative), trace group (urine dipstick trace) and positive group (urine dipstick ≥ 1 +). The primary outcomes were CIN non-recovery (a decrease of serum creatinine which remains ≥ 25% or 0.5 mg/dL over baseline at 1 week-12 months after PCI in patients inflicted with CIN). The odds ratio (OR) of CIN non-recovery was analyzed by logistic regression using the negative urine dipstick group as the reference group. RESULTS: Overall, 88 (16.0%) patients had trace urinary albumin, 74 (13.5%) patients had positive urinary albumin and 40 (7.3%) patients developed CIN non-recovery. Patients with positive urinary albumin had significantly higher incidence of CIN non-recovery [negative (3.4%), trace (11.4%) and positive (23.0%), respectively; P < 0.0001]. Multivariate analysis showed that trace and positive urinary albumin were associated with an increased risk of CIN non-recovery (trace vs negative: OR 2.88, P = 0.022; positive vs negative: OR 2.99, P = 0.021). These associations were consistent in subgroups of patients stratified by CIN non-recovery risk predictors. And CIN non-recovery was associated with an increased risk of long-term mortality during a mean follow-up period of 703 days (P < 0.001). CONCLUSION: Preprocedural albuminuria was associated with CIN non-recovery in patients undergoing PCI.

6.
Front Public Health ; 9: 619164, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681132

RESUMO

Children of immigrants are often considered to be at increased risk of mental health problems due to families' immigration-related stress and perceived discrimination and prejudice from the host country. However, many studies found them to have better developmental outcomes than children with native-born parents in the U.S. This study aims to unfold this paradoxical phenomenon using data from a population-based cohort of children born in large U.S. cities. Specifically, we investigated differences in mental health outcomes between children of immigrants and those with native-born parents, stratified by children's race-ethnicity. We also explored the mediating role of child maltreatment risk in the association of parental nativity status and race-ethnicity with children's mental health. Our findings supported the immigrant paradox, with better self-reported and parent-reported internalizing and externalizing outcomes in Hispanic and Black children of immigrants than their same race-ethnicity peers and White children of native-born. Such immigrant-native variations were partially explained by parents' physically and psychologically abusive behaviors. Hispanic and Black children with immigrant parents were less likely to be physically or psychologically abused than their peers of native-born at ages 4-5, which translated into mental health advantages of children of immigrants at age 9. Our findings shed light on future research to further clarify the mechanism underlying different parenting practices between same race-ethnicity immigrants and native-born families so that culturally responsive interventions can be developed to safeguard racial-ethnic minority children's mental health.

7.
Toxicol Appl Pharmacol ; 418: 115481, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33722666

RESUMO

Since its discovery, anthraquinone has become very valuable as a lead compound in the development of anti-cancer drugs. Previously, we designed and synthesized a new type of amide anthraquinone derivative (1-nitro-2-acylanthraquinone glycine, C10) with good activity against colon cancer. However, its effect and the underlying mechanism are unclear. In this study, C10 significantly inhibited the proliferation of HCT116 and HT29 colon cancer cells by blocking the cell cycle at the G2/M phase. C10 also plays a role in cell cycle arrest by reducing the protein and gene expression levels of cyclin B1 and its downstream signaling molecule cyclin-dependent kinase (CDK1). In addition, molecular docking studies showed that C10 has high affinity for Jak2, the first target in the cell cycle-related Jak2/Stat3 signaling pathway. Furthermore, C10 downregulated the expression of Jak2/Stat3 signaling pathway-related signaling molecules proteins and genes, and up-regulated the expression of PIAS-3, the upstream signaling molecule of Stat3, thereby down-regulating Stat3 phosphorylation. C10 reversed the expression of Jak2/Stat3 signaling pathway-related molecules activated by IL-6. Overall, our results indicate for the first time that C10 induces cell cycle arrest and inhibits cell proliferation by inhibiting the Jak2/Stat3 signaling pathway. This study provides new insights into the potential role of Jak2/Stat3 in the regulating cell cycle-related signaling pathways that mediate the inhibitory effects of C10 on colon cancer cell proliferation.

8.
Biomed Pharmacother ; 137: 111296, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33545663

RESUMO

OBJECTIVES: Aneurysms are generally the result of dilation of all 3 layers of the vessel wall, and pseudoaneurysms are the result of localized extravasation of blood that is contained by surrounding tissue. Since there is still no recommended protocol to decrease aneurysm formation and progression, we hypothesised that intramural delivery of TGF ß1 hydrogel can decrease aneurysm and pseudoaneurysm formation and progression. MATERIALS: Male C57BL/6 J mice (12-14 wk), SD rats (200 g) and pig abdominal aortas were used, and hydrogels were fabricated by the interaction of sodium alginate (SA), hyaluronic acid (HA) and CaCO3. METHODS: A CaCl2 adventitial incubation model in mice and a decellularized human great saphenous vein patch angioplasty model in rats were used. TGF ß1 hydrogel was intramurally delivered after CaCl2 incubation in mice; at day 7, the abdomen in some mice was reopened, and TGF ß1 hydrogel was injected intramurally into the aorta. In rats, TGF ß1 hydrogel was delivered intramurally after patch angioplasty completion. Tissues were harvested at day 14 and analysed by histology and immunohistochemistry staining. The pig aorta was also intramurally injected with hydrogel. RESULTS: In mice, rhodamine hydrogel was still found between the medium and adventitia at day 14. In the mouse aneurysm model, there was a thicker wall and smaller amount of elastin breaks in the TGF ß1 hydrogel-delivered groups both at day 0 and day 7 after CaCl2 incubation, and there were larger numbers of p-smad2- and TAK1-positive cells in the TGF ß1 hydrogel-injected groups. In the rat decellularized human saphenous vein patch pseudoaneurysm model, there was a higher incidence of pseudoaneurysm formation when the patch was decellularized using 3% SDS, and delivery of TGF ß1 hydrogel could effectively decrease the formation of pseudoaneurysm formation and increase p-smad2 and TAK1 expression. In pig aortas, hydrogels can be delivered between the medium and adventitia easily and successfully. CONCLUSIONS: Intramural delivery of TGF ß1 hydrogel can effectively decease aneurysm and pseudoaneurysm formation and progression in both mice and rats, and pig aortas can also be successfully intramurally injected with hydrogel. This technique may be a promising drug delivery method and therapeutic choice to decrease aneurysm and pseudoaneurysm formation and progression in the clinic.

9.
Child Abuse Negl ; : 104988, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33583625

RESUMO

BACKGROUND: Extensive research has documented the importance of neighborhood contextual factors in shaping maltreatment risk. Evidence is limited about the role of economic inequality within neighborhoods, which has increased substantially in the US over the past decade. OBJECTIVE: This study examines the relationship between neighborhood-level inequality and child maltreatment risk, paying particular attention to the cross-level interactions between neighborhood inequality and family income. PARTICIPANTS AND SETTING: A population-based cohort of 4,898 children born in large US cities was sampled in 1998-2000 and followed up at ages 1, 3, 5, and 9. METHOD: A set of regression models was analyzed to estimate the associations of family income, neighborhood inequality (operationalized as terciles of the Gini coefficient), and the interaction of these with child maltreatment risk, operationalized as physical abuse, psychological abuse, neglect, CPS involvement, and spanking. RESULTS: Low-income was associated with higher risks of neglect and CPS involvement, but not physical abuse, psychological abuse, or spanking. Among low-income families, higher neighborhood inequality was associated with lower likelihood of spanking. Among higher-income families, higher neighborhood inequality levels were associated with higher risks of physical abuse, yet lower risks of psychological abuse. CONCLUSION: Our findings align with previous studies showing mixed results on the relationship between neighborhood inequality and health outcomes. Those results may suggest that the effect of low-income itself is more important than the neighborhood context. Further research is needed to identify the determinants of inequality at the neighborhood level and the underlying mechanisms of its association with child maltreatment risks.

10.
Scientometrics ; : 1-27, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33612885

RESUMO

To encourage research transparency and replication, more and more journals have been requiring authors to share original datasets and analytic procedures supporting their publications. Does open data boost journal impact? In this article, we report one of the first empirical studies to assess the effects of open data on journal impact. China Industrial Economics (CIE) mandated authors to open their research data in the end of 2016, which is the first to embrace open data among Chinese journals and provides a natural experiment for policy evaluation. We use the data of 37 Chinese economics journals from 2001 to 2019 and apply synthetic control method to causally estimate the effects of open data, and our results show that open data has significantly increased the citations of journal articles. On average, the current- and second-year citations of articles published with CIE have increased by 1 ~ 4 times, and articles published before the open data policy also benefited from the spillover effect. Our findings suggest that journals can leverage compulsory open data to develop reputation and amplify academic impacts.

11.
BMJ Open ; 11(1): e040055, 2021 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455925

RESUMO

INTRODUCTION: Brain tumours encompass a complex group of intracranial tumours that mostly affect young adults and children, with a high incidence rate and poor prognosis. It remains impossible to systematically collect data on patients with brain tumours in China and difficult to perform in-depth analysis on the status of brain tumours, medical outcomes or other important medical issues through a multicentre clinical study. This study describes the first nation-wide data platform including the entire spectrum of brain tumour entities, which will allow better management and more efficient application of patient data in China. METHODS AND ANALYSIS: The National Brain Tumor Registry of China (NBTRC) is a registry of real-word clinical data on brain tumours. It is established and managed by the China National Clinical Research Center for Neurological Diseases and administered by its scientific and executive committees. The 54 participating hospitals of the NBTRC are located in 27 provinces/municipalities, performing more than 40 000 brain tumour surgeries per year. The data consist of in-hospital medical records, images and follow-up information after discharge. Data can be uploaded in three ways: the web portal, remote physical servers and offline software. The data quality control scheme is seven-dimensional. Each participating hospital could focus on a single pathology subtype and public subtypes of brain tumour for which they expect to conduct related multicentre clinical research. The standardised workflow to conduct clinical research is based on the benefit-sharing mechanism. Data collection will be conducted continuously from 1 February 2019 to 31 January 2024. ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. Consent for the adolescents' participation will be also obtained from their guardians via written consent. The results will be published in professional journals, in both Chinese and English. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900021096).

12.
BMC Microbiol ; 21(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407134

RESUMO

BACKGROUND: The widespread distribution of antimicrobial-resistant Shigella has become a recurrent challenge in many parts of the developing world. Previous studies indicate that the host of Shigella has expanded from humans to animals. This study aimed to investigate the prevalence of fluoroquinolone resistance and associated molecular characterization of S. dysenteriae 1 isolated from calves. RESULTS: All 38 unduplicated S. dysenteriae 1 isolates were collected from calves in Gansu Province from October 2014 to December 2016. According to MLST and PFGE analysis, these isolates were separated into 4 and 28 genotypes, respectively. The most common STs identified were ST228 (34.21%, 13/38) and ST229 (39.47%, 15/38), which were first found in the present study. All isolates harbored virulence genes, and the incidence of the seven virulence genes were ipaH (100%), ipaBCD (92.11%), stx (73.68%), ial (57.89%), sen (28.95%), set1A and set1B (0%). According to the results of antimicrobial susceptibilities, 76.32% (29/38) were resistant to fluoroquinolone and showed multidrug resistance. In a study on the polymorphism of quinolone resistance-determining region (QRDR) of gyrA/B and parC/E genes, we identified two mutations in gyrA (Ser83 → Leu and Asp87 → Asn) and parC (Ser80 → Ile and Ser83 → Leu), respectively. Among them, 55.17% (16/29) of resistant strains had the gyrA point mutations (Ser83 → Leu) and parC point mutation (Ser83 → Leu). Moreover, 41.38% (12/29) of isolates had all five point mutations of gyrA and parC. In addition, the prevalence of the plasmid-mediated quinolone resistance (PMQR) determinant genes was also investigated. All 29 fluoroquinolone-resistant isolates were positive for the aac (6')-Ib-cr gene but negative for qepA, except for SD001. In addition, only 6 (20.69%, 6/29) isolates harbored the qnr gene, including two with qnrB (6.90%, 2/29) and four with qnrS (13.79%, 4/29). CONCLUSION: Given the increased common emergence of multidrug resistant isolates, uninterrupted surveillance will be necessary to understand the actual epidemic burden and control this infection.

13.
Angle Orthod ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492395

RESUMO

OBJECTIVES: To observe skeletal width changes after mini-implant-assisted rapid maxillary expansion (MARME) and determine the possible factors that may affect the postexpansion changes using cone-beam computed tomography (CBCT) in young adults. MATERIALS AND METHODS: Thirty-one patients (mean age 22.14 ± 4.76 years) who were treated with MARME over 1 year were enrolled. Four mini-implants were inserted in the midpalatal region, and the number of activations ranged from 40 to 60 turns (0.13 per turn). CBCT was performed before MARME (T0), after activation (T1), and after 1 year of retention (T2). The mean period between T1 and T0 was 6 ± 1.9 months and between T2 and T1 was 13 ± 2.18 months. A paired t-test was performed to compare T0, T1, and T2. The correlations between the postexpansion changes and possible contributing factors were analyzed by Pearson correlation analysis. RESULTS: The widths increased significantly after T1. After T2, the palatal suture width decreased from 2.50 mm to 0.75 mm. From T1 to T2, decreases recorded among skeletal variables varied from 0.13 mm to 0.41 mm. This decrease accounted for 5.75% of the total expansion (2.26 mm) in nasal width (N-N) and 19.75% at the lateral pterygoid plate. A significant correlation was found between postexpansion change and palatal cortical bone thickness and inclination of the palatal plane (ANS-PNS/SN; P < .05). CONCLUSIONS: Expanded skeletal width was generally stable after MARME. However, some amount of relapse occurred over time. Patients with thicker cortical bone of the palate and/or flatter palatal planes seemed to demonstrate better stability.

14.
Neurosurg Focus ; 50(1): E10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386023

RESUMO

OBJECTIVE: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) have the ability to noninvasively visualize changes in white matter tracts, as well as their relationships with lesions and other structures. DTI/DTT has been increasingly used to improve the safety and results of surgical treatment for lesions in eloquent areas, such as brainstem cavernous malformations. This study aimed to investigate the application value of DTI/DTT in brainstem glioma surgery and to validate the spatial accuracy of reconstructed corticospinal tracts (CSTs). METHODS: A retrospective analysis was performed on 54 patients with brainstem gliomas who had undergone surgery from January 2016 to December 2018 at Beijing Tiantan Hospital. All patients underwent preoperative DTI and tumor resection with the assistance of DTT-merged neuronavigation and electrophysiological monitoring. Preoperative conventional MRI and DTI data were collected, and the muscle strength and modified Rankin Scale (mRS) score before and after surgery were measured. The surgical plan was created with the assistance of DTI/DTT findings. The accuracy of DTI/DTT was validated by performing direct subcortical stimulation (DsCS) intraoperatively. Multiple linear regression was used to investigate the relationship between quantitative parameters of DTI/DTT (such as the CST score and tumor-to-CST distance [TCD]) and postoperative muscle strength and mRS scores. RESULTS: Among the 54 patients, 6 had normal bilateral CSTs, 12 patients had unilateral CST impairments, and 36 had bilateral CSTs involved. The most common changes in the CSTs were deformation (n = 29), followed by deviation (n = 28) and interruption (n = 27). The surgical approach was changed in 18 cases (33.3%) after accounting for the DTI/DTT results. Among 55 CSTs on which DsCS was performed, 46 (83.6%) were validated as spatially accurate by DsCS. The CST score and TCD were significantly correlated with postoperative muscle strength (r = -0.395, p < 0.001, and r = 0.275, p = 0.004, respectively) and postoperative mRS score (r = 0.430, p = 0.001, and r = -0.329, p = 0.015, respectively). The CST score was independently linearly associated with postoperative muscle strength (t = -2.461, p = 0.016) and the postoperative mRS score (t = 2.052, p = 0.046). CONCLUSIONS: DTI/DTT is a valuable tool in the surgical management of brainstem gliomas. With good accuracy, it can help optimize surgical planning, guide tumor resection, and predict the postoperative muscle strength and postoperative quality of life of patients.

15.
BMC Surg ; 21(1): 27, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407329

RESUMO

BACKGROUND: Primary facial spasm accompanied by arrhythmia is a rare clinical phenomenon and has not been reported before. We describe this phenomenon and discuss its mechanism and treatment. CASE PRESENTATION: We herein present a rare case of a patient with left primary facial spasm and a third-degree atrioventricular block (III degree AVB), who was implanted with a temporary cardiac pacemaker to receive microvascular decompression (MVD) because of refusal of a permanent cardiac pacemaker. The symptoms of facial spasm disappeared after MVD. The temporary cardiac pacemaker was removed on the second day after surgery. Her ECG still showed the third-degree atrioventricular block after a follow-up period of 5 months. CONCLUSIONS: We are the first to report a patient with facial spasm and arrhythmia who was implanted with a temporary cardiac pacemaker to receive MVD. This case report demonstrated that the concomitant presence of a III degree AVB maybe not a contraindication for MVD, and the etiology of this facial spasm was the actual vascular compression of the facial nerve entry zone that was not related to the atrioventricular block.


Assuntos
Arritmias Cardíacas , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Marca-Passo Artificial , Feminino , Espasmo Hemifacial/etiologia , Espasmo Hemifacial/cirurgia , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Methods Mol Biol ; 2194: 223-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32926369

RESUMO

Intrinsic and acquired drug resistance is a major challenge in cancer therapy. Synergistic drug combinations could help to overcome drug resistance. However, the number of possible drug combinations is enormous, and it is infeasible to experimentally screen all drug combinations with limited resources. Therefore, computational models to predict and prioritize effective drug combinations are important for combination therapy discovery. Compared with existing models, we propose a novel deep learning model, AuDNNsynergy, to predict the synergy of pairwise drug combinations by integrating multiomics data. Specifically, three autoencoders are trained using the gene expression, copy number, and genetic mutation data of tumor samples from The Cancer Genome Atlas (TCGA). Then the gene expression, copy number, and mutation of individual cancer cell lines are coded using the three trained autoencoders. The physicochemical features of individual drugs and the encoded omics data of individual cancer cell lines are used as the input features of a deep neural network that predicts the synergy score of given pairwise drug combinations against the specific cancer cell lines. The comparison results showed the proposed AuDNNsynergy model outperforms, specifically in terms of rank correlation metric, four state-of-the-art approaches, namely, DeepSynergy, Gradient Boosting Machines, Random Forests, and Elastic Nets.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/química , Biologia Computacional/métodos , Aprendizado Profundo , Neoplasias/genética , Linhagem Celular Tumoral , Simulação por Computador , Bases de Dados Factuais , Bases de Dados Genéticas , Combinação de Medicamentos , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Redes Neurais de Computação
17.
J Clin Neurosci ; 83: 25-30, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33342626

RESUMO

Surgical resection of lesions located in the ventral midbrain is challenging. Few approaches and safe entry zones (SEZs) have been proposed and used to remove this type of lesion, and each has its limitations. Using two illustrating cases, the authors describe a trans-lamina terminalis suprategmental approach for removing ventral midbrain lesions. This approach provides a straight surgical trajectory with sparse neurovascular structures and can be performed with a standard pterional or subfrontal craniotomy. It may be the ideal approach for ventromedial midbrain lesions extending towards the third ventricle.


Assuntos
Hipotálamo/cirurgia , Mesencéfalo/cirurgia , Procedimentos Neurocirúrgicos/métodos , Craniotomia , Humanos , Masculino , Terceiro Ventrículo/cirurgia
18.
Hum Gene Ther ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33339472

RESUMO

Ovarian cancer is the most lethal gynecological cancer, most patients relapse within 12-24 months, and eventually die, especially platinum-resistant patients. Gene therapy has been one of the most potential methods for tumor treatment. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. Sodium iodide symporter (NIS) is an intrinsic membrane glycoprotein and can concentrate 131I, which is important for radionuclide therapy and nuclear medicine imaging in recent years. However, the rapid iodine efflux has become a bottleneck for NIS-mediated radionuclide gene therapy. Our previous studies found that the early growth response-1 (Egr1) promoter containing CC(A/T)6GG (CArG) elements had an 131I radiation-positive feedback effect on the NIS gene. Other research showed the synthesized Egr1 promoter containing four CArG elements, E4, was nearly three times as sensitive as the Egr1 promoter. In our study, BMSC-E4-NIS was engineered to express NIS under the control of E4 promoter using lentivirial vectors. After BMSC-E4-NIS implantation, no tumors were seen in BALB/c nude mice and BMSC-E4-NIS did not promote the growth of SKOV3 tumor. BMSCs migrated toward ovarian cancer samples in chemotaxis assays and to ovarian tumors in mice. Using micro-single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, we found that E4 promoter produced a notable increase in 125I uptake after 131I irradiation, the radionuclide uptake is almost three and six times more than Egr1 and cytomegalovirus (CMV) promoters. These studies confirmed the feasibility of using BMSCs as carriers for lentivirus-mediated E4-NIS gene therapy for ovarian cancer. Further research on BMSC-E4-NIS gene therapy for ovarian cancer in vivo will also be carried on, and if successful, this might provide a new adjuvant therapeutical option for platinum-resistant ovarian cancer patients and provide a new method for dynamic evaluation of curative effect.

19.
Sci Total Environ ; 757: 143918, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33316525

RESUMO

Riverine nitrogen loss makes a large contribution to the global nitrogen budget. However, little research has focused on nitrogen loss from large turbid rivers with high suspended sediment (SPS) concentrations. In this work, nitrogen loss amounts and related drivers were studied across fluvial networks of the Yellow River, the largest turbid river in the world, based on in situ measurement of nitrogen gas (N2) and nitrous oxide (N2O) fluxes at the water-air interface via the diffusion model and floating chamber methods, respectively. The results showed that N2 and N2O fluxes from the Yellow River ranged from -2.93 to 48.54 mmol m-2 d-1 and from 2.42 to 712.23 µmol m-2 d-1, respectively, with the nitrogen loss amount estimated to be 5.56 × 107 kg N yr-1 for the Yellow River, including the mainstem and main tributaries. Other than nitrogen compounds and water temperature, nitrogen loss from the Yellow River was also affected by SPS. Both N2 flux: DIN and N2O flux: DIN ratios increased remarkably in the middle reaches, probably due to a sharp increase of SPS concentration in this section. Furthermore, greater SPS concentrations were a main cause for the higher N2O flux in the middle reaches than those in the other reaches of the Yellow River, and the possible effect of SPS was stronger on N2O flux than on N2 flux. This study demonstrates the importance of SPS in nitrogen loss from large turbid rivers, and more research is demanded to further clarify the role of SPS in riverine nitrogen cycle.

20.
Nat Biomed Eng ; 4(12): 1150-1158, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33273714

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and accurate nucleic acid detection at the point of care. Here, we report an amplification-free nucleic acid immunoassay, implemented on a lateral flow strip, for the fluorescence detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in less than one hour. The assay uses DNA probes that are designed to bind to the conserved open reading frame 1ab (ORF1ab), envelope protein (E) and the nucleocapsid (N) regions of the SARS-CoV-2 genome, and a fluorescent-nanoparticle-labelled monoclonal antibody that binds to double-stranded DNA-RNA hybrids. In a multi-hospital randomized double-blind trial involving 734 samples (593 throat swabs and 141 sputum) provided by 670 individuals, the assay achieved sensitivities of 100% and specificities of 99% for both types of sample (ground truth was determined using quantitative PCR with reverse transcription). The inexpensive amplification-free detection of SARS-CoV-2 RNA should facilitate the rapid diagnosis of COVID-19 at the point of care.

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