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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5464-5467, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019216

RESUMO

In vitro cytotoxicity screening is a crucial step of anticancer drug discovery. The application of deep learning methodology is gaining increasing attentions in processing drug screening data and studying anticancer mechanisms of chemical compounds. In this work, we explored the utilization of convolutional neural network in modeling the anticancer efficacy of small molecules. In particular, we presented a VGG19 model trained on 2D structural formulae to predict the growth-inhibitory effects of compounds against leukemia cell line CCRF-CEM, without any use of chemical descriptors. The model achieved a normalized RMSE of 15.76% on predicting growth inhibition and a Pearson Correlation Coefficient of 0.72 between predicted and experimental data, demonstrating a strong predictive power in this task. Furthermore, we implemented the Layer-wise Relevance Propagation technique to interpret the network and visualize the chemical groups predicted by the model that contribute to toxicity with human-readable representations.Clinical relevance-This work predicts the cytotoxicity of chemical compounds against human leukemic lymphoblast CCRF-CEM cell lines on a continuous scale, which only requires 2D images of the structural formulae of the compounds as inputs. Knowledge in the structure-toxicity relationship of small molecules will potentially increase the hit rate of primary drug screening assays.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33054414

RESUMO

INTRODUCTION: Patients with cancer are more vulnerable to COVID-19 than the general population. Accordingly, it is necessary to identify the risk factors for death in patients with cancer and COVID-19. METHODS: PubMed, Cochrane Library, and Embase Ovid databases were searched for relevant articles published before July 31st, 2020. Studies that explored the risk factors for mortality were included. The effect size was relative risk (RR) and 95% confidence interval (CI). RESULTS: We included 17 observational studies involving 3268 patients. The pooled mortality was 24.8%. Male gender, age above 65 years, and comorbidities (especially hypertension and COPD) were risk factors for death (RR 1.16, 1.27, 1.12; 95% CI 0.7-1.95, 1.08-1.49, 1.04-1.2; P=0.006, 0.004 and 0.002, respectively). Recent anti-cancer treatments did not increase mortality (P> 0.05). Dyspnea, cough, and sputum were associated with an elevated risk of death (P< 0.05). Antibiotics, glucocorticoids, interferons, invasive ventilation, and complications were associated with a high probability of death (P< 0.05). CONCLUSIONS: Various demographic and clinical characteristics, such as male gender, advanced age, comorbidities, and symptoms, were identified as risk factors for mortality in patients with cancer and COVID-19. Our findings suggest recent anti-cancer treatments do not increase mortality. TRIAL REGISTRATION: Registration in PROSPERO (CRD42020201514).

3.
Int J Surg ; 83: 206-215, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022414

RESUMO

BACKGROUND: Studies have provided controversial and limited knowledge regarding the impact of sarcopenia on surgical outcomes in esophageal cancers due to retrospective study designs and single muscle-mass assessment. This prospective cohort study aimed to resolve these issues. METHODS: Bioelectrical impedance analysis, handgrip strength measurement, and the 4-m walking test were conducted before surgery. Sarcopenia was diagnosed as low appendicular skeletal muscle mass index (<7.0 kg/m2 in men and <5.7 kg/m2 in women) plus low handgrip strength (<26 kg in men and <18 kg in women) and/or low gait speed (<0.8 m/s). Presarcopenia was diagnosed as either: (1) solely low muscle mass index; or (2) solely low handgrip strength and/or gait speed. Endpoints included perioperative biochemical indicators, postoperative complications, and the recovery of postoperative quality of life (QOL). RESULTS: In total, 212 patients were enrolled, including 55 (25.9%) and 60 (28.3%) patients diagnosed with sarcopenia and presarcopenia, respectively. The presarcopenic and normal patients showed a similar risk of postoperative complications and were combined. Despite similar baseline levels, sarcopenic patients (vs. non-sarcopenic) showed decreased prealbumin on postoperative day (POD) 1, decreased albumin on PODs 1, 3, and 5, and delayed recovery of lymphocyte counts (all P < 0.05). The levels of C-reactive protein in sarcopenic patients was lower than in non-sarcopenic patients on POD 1 (P = 0.010) but higher on POD 5 (P = 0.001). Multivariate analyses demonstrated the independent predictive value of sarcopenia for overall complications (P < 0.001), major complications (Clavien-Dindo grade ≥ III, P = 0.001), and delayed hospital discharge (>12 days, P < 0.001). Sarcopenia was demonstrated as a risk factor for deteriorated global QOL (P = 0.001), physical (P = 0.001) and role functions (P = 0.006), and severe fatigue (P = 0.004) at four weeks after surgery. CONCLUSIONS: Sarcopenia was associated with poor metabolic stress and immune responses surrounding esophagectomy and was a potential target for reducing complications and promoting recovery of QOL.

4.
Dis Markers ; 2020: 8854700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062073

RESUMO

During cardiopulmonary bypass (CPB), pulmonary ischemia/reperfusion (I/R) injury can cause acute lung injury (ALI). Our previous research confirmed that abnormal high-mobility group box 1 (HMGB1) release after CPB was closely related to ALI. However, the mechanism underlying the HMGB1-mediated induction of ALI after CPB is unclear. Our previous study found that HMGB1 binds Toll-like receptor 4 (TLR4), leading to lung injury, but direct evidence of a role for these proteins in the mechanism of CPB-induced lung injury has not been shown. We examined the effects of inhibiting HMGB1 or reducing TLR4 expression on CPB-induced lung injury in rats administered anti-HMBG1 antibody or TLR4 short-hairpin RNA (shTLR4), respectively. In these rat lungs, we studied the histologic changes and levels of interleukin- (IL-) 1ß, tumour necrosis factor- (TNF-) α, HMGB1, and TLR4 after CPB. After CPB, the lung tissues from untreated rats showed histologic features of injury and significantly elevated levels of IL-1ß, TNF-α, HMGB1, and TLR4. Treatment with anti-HMGB1 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1ß, TNF-α, HMGB1, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB. Treatment with shTLR4 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1ß, TNF-α, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB, but could not alleviate the HMGB1 protein levels induced by CPB. In summary, the present study demonstrated that the HMGB1/TLR4 pathway mediated the development of ALI induced by CPB.

5.
Biomed Res Int ; 2020: 2495157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062672

RESUMO

Clear cell renal cell carcinoma (ccRCC) accounts for more than 75% of renal cell carcinoma. Nearly 25% of ccRCC patients were diagnosed with metastasis. Though the genomic profile of ccRCC has been widely studied, the difference between localized and metastatic ccRCC was not clarified. Primary tumor samples and matched whole blood were collected from 106 sporadic patients diagnosed with renal clear cell carcinoma at Qilu Hospital of Shandong University from January 2017 to November 2019, and 17 of them were diagnosed with metastasis. A hybridization capture-based next-generation sequencing of 618 cancer-related genes was performed to investigate the somatic and germline variants, tumor mutation burden (TMB), and microsatellite instability (MSI). Five genes with significantly different prevalence were identified in the metastatic group, especially TOP1 (17.65% vs. 0%) and SNCAIP (17.65% vs. 0%). The altered frequency of PBRM1 (0% vs. 27%) and BAP1 (24% vs. 10%) differed between the metastatic and nonmetastatic groups, which may relate to the prognosis. Of these 106 patients, 42 patients (39.62%) had at least one alteration in DNA damage repair (DDR) genes, including 58.82% of metastatic ccRCC patients and 35.96% of ccRCC patients without metastasis. Ten pathogenic or likely pathogenic (P/LP) variants were identified in 11 sporadic clear cell renal cell carcinoma patients (10.38%), including rarely reported ATM (n=1), MUTYH (n=1), NBN (n=1), RAD51D (n=1), and BRCA2 (n=1). No significant difference in the ratio of P/LP variant carriers or TMB was identified between the metastatic and nonmetastatic groups. We found a unique genomic feature of Chinese metastatic ccRCC patients with a higher prevalence of alterations in DDR, TOP1, and SNCAIP. Further investigated studies and drug development are needed in the future.

6.
Adv Mater ; : e2004398, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33063391

RESUMO

The sensory nervous system (SNS) builds up the association between external stimuli and the response of organisms. In this system, habituation is a fundamental characteristic that filters out irrelevantly repetitive information and makes the SNS adapt to the external environment. To emulate this critical process in electronic devices, a Lix SiOy -based memristor (TiN/Lix SiOy /Pt) is developed where the temporal response under repetitive stimulation is similar to that of habituation. By connecting this synaptic device to a leaky integrate-and-fire neuron based on a Ag/SiO2 :Ag/Au memristor, a fully memristive SNS with habituation is experimentally demonstrated. Finally, a habituation spiking neural network based on the SNS is built and its application in obstacle avoidance for robot navigation is successfully presented. The results provide that a direct emulation of the biologically inspired learning process by memristors could be a sound choice for neuromorphic hardware implementation.

7.
J Magn Reson Imaging ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33034113

RESUMO

BACKGROUND: The progression of atherosclerotic plaque is a dynamic process; however, the natural evolution process of plaque enhancement on MRI remains unclear. PURPOSE: To evaluate changes in enhancement characteristics of middle cerebral arterial (MCA) atherosclerotic plaques over time using MRI and to explore the relationship between the changes in plaque enhancement and stroke recurrence. STUDY TYPE: Prospective. POPULATION: Fifty-four patients with MCA atherosclerotic plaque underwent initial and follow-up examinations with a median interval of 519 days (range 84-1820 days), including 37 males and 16 patients with recurrent stroke. FIELD STRENGTH/SEQUENCE: Time-of-flight magnetic resonance angiography, diffusion-weighted imaging, T2 -weighted imaging, pre- and postcontrast T1 -weighted imaging at 3 T. ASSESSMENT: Clinical characteristics and differences in the changes in plaque enhancement among acute, subacute and chronic stroke groups and the changes in the degree of stenosis and plaque enhancement between the patients with and without recurrent stroke were compared. Risk factors for patients with recurrent stroke were assessed. Intra- and interobserver agreement in initial and the changes in plaque enhancement and stenosis, and the correlation between changes in plaque enhancement and recurrent stroke, were evaluated. STATISTICAL TESTS: Independent-samples t-test, Mann-Whitney U-test, chi-squared test, Spearman correlation, logistic regression and Cohen's kappa test. RESULTS: There were significant differences in the changes in stenosis and plaque enhancement (P < 0.05) between the patients with and without recurrent stroke. A significant correlation was observed between the changes in plaque enhancement and stroke recurrence (r = 0.415, P < 0.05). Multivariate regression analysis showed that a change in plaque enhancement was an independent factor for stroke recurrence after adjusting for confounding factors (odds ratio [OR] = 5.797, P < 0.05). There was excellent intra- and interobserver agreement in evaluating plaque enhancement and stenosis. DATA CONCLUSION: Stable or increased enhancement of MCA plaque was related to recurrent stroke events at follow-up. Change in plaque enhancement on MRI may be an important indicator for predicting recurrent stroke. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

8.
Nat Chem ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077928

RESUMO

Chemical reactions that convert sp2 to sp3 hybridization have been demonstrated to be a fascinating yet challenging route to functionalize graphene. So far it has not been possible to precisely control the reaction sites nor their lateral order at the atomic/molecular scale. The application prospects have been limited for reactions that require long soaking, heating, electric pulses or probe-tip press. Here we demonstrate a spatially selective photocycloaddition reaction of a two-dimensional molecular network with defect-free basal plane of single-layer graphene. Directly visualized at the submolecular level, the cycloaddition is triggered by ultraviolet irradiation in ultrahigh vacuum, requiring no aid of the graphene Moiré pattern. The reaction involves both [2+2] and [2+4] cycloadditions, with the reaction sites aligned into a two-dimensional extended and well-ordered array, inducing a bandgap for the reacted graphene layer. This work provides a solid base for designing and engineering graphene-based optoelectronic and microelectronic devices.

9.
Food Chem ; 341(Pt 1): 128211, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33032248

RESUMO

The physicochemical mechanism of starch digestion is very complicated since it may be affected by the non-valence interactions of the amylase inhibitor with the substrate or the enzyme. The role of hydrophobic interaction in the process of starch digestion is not clear. In this study, pluronics (PLs) with different hydrophobicity were used as model amphiphilic compounds to study their inhibition on starch digestion using multi-spectroscopic methods. The results showed that the hydrophobic nature of PLs changed starch structure, but it had a greater effect on the structure of α-amylase by exposing more tryptophan residues and increasing α-helix and ß-sheet contents. Further investigation by using different chain-length fatty acids confirmed the results. The finding in this study is informative to design and fabricate α-amylase inhibitors for controlling starch digestion at the molecular level.

10.
J Biomech ; 112: 110072, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33075666

RESUMO

Identification of runner's performance level is critical to coaching, performance enhancement and injury prevention. Machine learning techniques have been developed to measure biomechanical parameters with body-worn inertial measurement unit (IMU) sensors. However, a robust method to classify runners is still unavailable. In this paper, we developed two models to classify running performance and predict biomechanical parameters of 30 subjects. We named the models RunNet-CNN and RunNet-MLP based on their architectures: convolutional neural network (CNN) and multilayer perceptron (MLP), respectively. In addition, we examined two validation approaches, subject-wise (leave-one-subject-out) and record-wise. RunNet-MLP classified runner's performance levels with an overall accuracy of 97.1%. Our results also showed that RunNet-CNN outperformed RunNet-MLP and gradient boosting decision tree in predicting biomechanical parameters. RunNet-CNN showed good agreement (R2 > 0.9) with the ground-truth reference on biomechanical parameters. The prediction accuracy for the record-wise method was better than the subject-wise method regardless of biomechanical parameters or models. Our findings showed the viability of using IMUs to produce reliable prediction of runners' performance levels and biomechanical parameters.

11.
Anal Chem ; 92(20): 14259-14266, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32998507

RESUMO

Colorimetric analytical strategies exhibit great promise in developing on-site detection methods for antibiotics, while substantial recent research efforts remain problematic due to dissatisfactory sensitivity. Taking this into account, we develop a novel colorimetric sensor for in-field detection of antibiotics by using aptamer (Apt)-capped and horseradish peroxidise (HRP)-embedded zeolitic metal azolate framework-7 (MAF-7) (Apt/HRP@MAF-7) as target recognition and signal transduction, respectively. With the substrate 3,3',5,5'-tetramethylbenzidine (TMB)-impregnated chip attached on the lid, the assay can be conveniently operated in a tube and reliably quantified by a handheld colorimeter. Hydrophilic MAF-7 can not only prevent HRP aggregation but also enhance HRP activity, which would benefit its detection sensitivity. Besides, the catalytic activity of HRP@MAF-7 can be sealed through assembling with Apt and controllably released based on the bioresponsivity via forming target-Apt complexes. Consequently, a significant color signal can be observed owing to the oxidation of colorless TMB to its blue-green oxidized form oxTMB. As a proof-of-concept, portable detection of streptomycin was favorably achieved with excellent sensitivity, which is superior to most reported methods and commercial kits. The developed strategy affords a new design pattern for developing on-site antibiotics assays and immensely extends the application of enzyme embedded metal-organic framework composites.

12.
Acta Histochem ; 122(7): 151600, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33066828

RESUMO

OBJECTIVES: Aim of this study is to explore whether quercetin can inhibit the enlarged fibrogenic responses of endometrial stromal cells by increasing the level of microRNA-145 (miR-145) and mediating the TGFß1/Smad2/Smad3 signaling pathway, and to discuss the mechanism of signal transduction, further to provide experimental basis for revealing the pathophysiological mechanism and seeking new strategies for effective prevention and treatment of endometrial fibrosis. METHODS: The expression levels of miR-145 and TGF-ß receptor 2 (TGFBR2) were detected by RT-qPCR analysis. Expressions of α-smooth muscle actin (α-SMA) and vimentin were examined by immunofluorescence staining. Cell viability was measured by MTT assay. The protein expression of collagen type 1 alpha 1 (Col1a1), α-SMA, fibronectin (FN), TGFBR2, transforming growth factor (TGF-ß1), Smad2/3, phospho-Smad2/3 (p-Smad2/3) were detected by western blot analysis. The interaction between miR-145 and TGFBR2 was confirmed by dual-luciferase reporter gene assay. RESULTS: The expression level of miR-145 was decreased, whereas TGFBR2 was increased in intrauterine adhesion tissue. The expression levels of COL1A1, α-SMA, FN, TGFBR2, and p-Smad2/3 were increased, whereas miR-145 and cell proliferation were decreased in human endometrial stromal cells (hESCs) in response to TGF-ß1 stimulation in a time and dose-dependent manner, which could be reversed by quercetin. Furthermore, quercetin regulates cell fibrogenic responses of endometrial stromal cells via miR-145/TGF-ß1/Smad2/Smad3 pathway. CONCLUSIONS: These findings indicated that quercetin have a significant anti-fibrotic effect and could upregulate miR-145 and inhibit activation of TGF-ß1/Smad2/Smad3 pathway to regulate TGF-ß1 induced fibrogenic responses of endometrial stromal cells, which may serve as a potential therapeutic agent for endometrial fibrosis.

13.
Exp Anim ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33071271

RESUMO

Non-human primates are most suitable for generating cervical experimental models, and it is necessary to study the anatomy of the cervical spine in non-human primates when generating the models. The purpose of this study was to provide the anatomical parameters of the cervical spine and spinal cord in long-tailed macaques (Macaca fascicularis) as a basis for cervical spine-related experimental studies. Cervical spine specimens from 8 male adult subjects were scanned by micro-computed tomography, and an additional 10 live male subjects were scanned by magnetic resonance imaging. The measurements and parameters from them were compared to those of 12 male adult human subjects. Additionally, 10 live male subjects were scanned by magnetic resonance imaging, and the width and depth of the spinal cord and spinal canal and the thickness of the anterior and posterior cerebrospinal fluid were measured and compared to the relevant parameters of 10 male adult human subjects. The tendency of cervical parameters to change with segmental changes was similar between species. The vertebral body, spinal canal, and spinal cord were significantly flatter in the human subjects than in the long-tailed macaques. The cerebrospinal fluid space in the long-tailed macaques was smaller than that in the human subjects. The anatomical features of the cervical vertebrae of long-tailed macaques provide a reference for establishing a preclinical model of cervical spinal cord injury.

14.
J Affect Disord ; 278: 433-442, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33010568

RESUMO

BACKGROUND: Adolescent depression varies considerably in the course. However, there are no biobehavioral predictors of illness trajectories, and follow-up studies in depressed youth are sparse. Here we sought to examine whether reward function would predict future clinical outcomes in adolescents with depressive symptoms. We utilized the reward flanker fMRI task to assess brain function during distinct reward processes of anticipation, attainment and positive prediction error (PPE, i.e. receiving uncertain rewards). METHODS: Subjects were 29 psychotropic-medication-free participants with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two adolescents (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined symptom severity as predictors for follow-up clinical outcomes. Whole-brain analyses examined the relationships between neural reward processes and follow-up outcomes. RESULTS: Clinically, anhedonia, but not irritability, predicted future depression and suicidal ideations. Among reward processes, only neural activation during PPE was correlated with future depression and anhedonia severity. Specifically, activation in the left angular gyrus-a component of default mode network-was associated with future depression, while activation in the dorsal anterior cingulate, operculum and left insula-key regions within the salience and pain networks-was associated with future anhedonia, even when controlling baseline anhedonia. LIMITATIONS: Small sample size and variability in follow-up intervals limit the generalizability of conclusions. CONCLUSIONS: This research suggests the anhedonia and reward dysfunction may predict a worse course in adolescent depression. The adolescents with anhedonia should be monitored more carefully for a longer period.

15.
Adv Mater ; : e2003018, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079425

RESUMO

Spiking neural networks (SNNs) sharing large similarity with biological nervous systems are promising to process spatiotemporal information and can provide highly time- and energy-efficient computational paradigms for the Internet-of-Things and edge computing. Nonvolatile electrolyte-gated transistors (EGTs) provide prominent analog switching performance, the most critical feature of synaptic element, and have been recently demonstrated as a promising synaptic device. However, high performance, large-scale EGT arrays, and EGT application for spatiotemporal information processing in an SNN are yet to be demonstrated. Here, an oxide-based EGT employing amorphous Nb2 O5 and Lix SiO2 is introduced as the channel and electrolyte gate materials, respectively, and integrated into a 32 × 32 EGT array. The engineered EGTs show a quasi-linear update, good endurance (106 ) and retention, a high switching speed of 100 ns, ultralow readout conductance (<100 nS), and ultralow areal switching energy density (20 fJ µm-2 ). The prominent analog switching performance is leveraged for hardware implementation of an SNN with the capability of spatiotemporal information processing, where spike sequences with different timings are able to be efficiently learned and recognized by the EGT array. Finally, this EGT-based spatiotemporal information processing is deployed to detect moving orientation in a tactile sensing system. These results provide an insight into oxide-based EGT devices for energy-efficient neuromorphic computing to support edge application.

16.
J Magn Reson Imaging ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32864816

RESUMO

BACKGROUND: Noninvasive assessment of intracranial stenosis is important to manage ischemic stroke patients. However, few previous studies have compared 3D black-blood MRI with 3D time-of-flight (TOF), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) for intracranial artery plaque assessment. PURPOSE: To compare 3D black-blood MRI and 3D TOF-MRA, using DSA as the reference standard for intracranial stenosis and atherosclerotic plaque assessment in patients with posterior circulation stroke or transient ischemic attacks (TIAs). STUDY TYPE: Prospective, cohort study. POPULATION: One hundred and one patients with posterior circulation stroke and/or TIA (age 63 ± 10 years, 84 male) who underwent DSA and MRI within 4 weeks of each other. FIELD STRENGTH/SEQUENCE: 3D fast-spin-echo MRI for intracranial vessel wall imaging (IVWI) and 3D TOF at 3T. ASSESSMENT: Two radiologists independently measured the degree of stenosis on 3D IVWI and TOF, using DSA as a reference. Plaque enhancement was recorded when the plaque was stenosis-free on DSA. STATISTICAL TESTS: Shapiro-Wilk's test, Student's t-test, Mann-Whitney U-test, Spearman correlation, Bland-Altman analysis, and interclass correlation coefficient (ICC). RESULTS: A total of 238 intracranial plaques (203 posterior, 35 anterior) were included. 3D IVWI showed better agreement with DSA in measuring stenosis than TOF (ICC = 0.89 vs. 0.64). 3D IVWI had higher sensitivity and specificity for detecting stenosis >50% and stenosis >75% than TOF, using DSA as the standard. TOF significantly overestimated the degree of stenosis compared to DSA (65 ± 19% vs. 51 ± 15%, P < 0.001). DSA did not observe 62 nonstenotic plaques (26.1%) that were shown only on 3D IVWI, in which 36 plaques (58.1%) showed contrast enhancement. The interreader agreement for measuring stenosis were excellent, with ICCs >0.90 for all three modalities. DATA CONCLUSION: 3D black-blood MRI is accurate and reproducible for quantifying intracranial artery stenosis compared with DSA, and performs better than 3D TOF. As compared to DSA, it detects more nonstenotic plaques. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

17.
J Eukaryot Microbiol ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32865301

RESUMO

Green euglenophyte are a group of eukaryote with ancient origin. In order to understand the evolution of the group, it is interesting to know which characteristics are more primitive. Here, a phylogenetic tree of green euglenophytes based on the 18S rRNA gene was constructed, and ancestral states were reconstructed based on eight morphological characters. This research clarifies the phylogenetic relationships of green euglenophytes and provides a basis for the study of the origin of these plants. The phylogenetic tree, which was constructed by Bayesian inference, revealed that: Eutreptia and Eutreptiella were sister groups and that Lepocinclis, Phacus and Discoplastis were close relatives; Euglena, Cryptoglena, Monomorphina, and Colacium were closely related in addition to Trachelomonas and Strombomonas; and Euglena was not monophyletic. An ancestral reconstruction based on morphological characters revealed seven primitive character states: ductile surface, spirally striated, slightly narrowing or sharp elongated cauda, absence of a lorica, chloroplast lamellar, shield or large discoid, pyrenoid with sheath, and with many small paramylon grains. However, the ancestral state of the length of the flagellum could not be inferred. Euglena and Euglenaria, which both possessed all of the ancestral character states, might represent the most ancient lineages of green euglenophytes.

18.
ACS Nano ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32940463

RESUMO

We developed a custom-designed liposome carrier for codelivery of a potent immunogenic cell death (ICD) stimulus plus an inhibitor of the indoleamine 2,3-dioxygenase (IDO-1) pathway to establish a chemo-immunotherapy approach for solid tumors in syngeneic mice. The carrier was constructed by remote import of the anthraquinone chemotherapeutic agent, mitoxantrone (MTO), into the liposomes, which were further endowed with a cholesterol-conjugated indoximod (IND) prodrug in the lipid bilayer. For proof-of-principle testing, we used IV injection of the MTO/IND liposome in a CT26 colon cancer model to demonstrate the generation of a robust immune response, characterized by the appearance of ICD markers (CRT and HMGB-1) as well as evidence of cytotoxic cancer cell death, mediated by perforin and granzyme B. Noteworthy, the cytotoxic effects involved natural killer (NK) cell, which suggests a different type of ICD response. The immunotherapy response was significantly augmented by codelivery of the IND prodrug, which induced additional CRT expression, reduced number of Foxp3+ Treg, and increased perforin release, in addition to extending animal survival beyond the effect of an MTO-only liposome. The outcome reflects the improved pharmacokinetics of MTO delivery to the cancer site by the carrier. In light of the success in the CT26 model, we also assessed the platform efficacy in further breast cancer (EMT6 and 4T1) and renal cancer (RENCA) models, which overexpress IDO-1. Encapsulated MTO delivery was highly effective for inducing chemo-immunotherapy responses, with NK participation, in all tumor models. Moreover, the growth inhibitory effect of MTO was enhanced by IND codelivery in EMT6 and 4T1 tumors. All considered, our data support the use of encapsulated MTO delivery for chemo-immunotherapy, with the possibility to boost the immune response by codelivery of an IDO-1 pathway inhibitor.

19.
Magn Reson Med ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32970911

RESUMO

PURPOSE: This paper studies the RF-induced heating for modular external fixation devices applied on the leg regions of the human bodies. Through numerical investigations of RF-induced heating related to different patient orientations, landmark positions, and device positions under 1.5T and 3T MRI systems, simple and practical methods to reduce RF-induced heating are recommended. METHODS: Numerical simulations using a full-wave electromagnetic solver based on the finite-difference time-domain method were performed to characterize the effects of patient orientations (head-first/feet-first), landmark positions (the scanning area of the patient), and device positions (device on left or right leg) on the RF-induced heating of the external fixation devices. The G32 coil design and three anatomical human models (Duke model, Ella model, and Fats model) were adopted to model the MRI RF coil and the patients. RESULTS: The relative positions of the patient, device, and coil can significantly affect the RF-induced heating. With other conditions remaining the same, changing the device position or patient orientation can lead to a peak 1-g averaged spatial absorption ratio variation of a factor around four. By changing the landmark position and the patient orientation, the RF-induced heating can be reduced from 1323.6 W/kg to 217.5 W/kg for the specific scanning situations studied. CONCLUSION: Patient orientations, landmark positions, and device positions influence the RF-induced heating of modular external fixation devices at 1.5 T and 3 T. These features can be used to reduce the RF-induced heating during MRI simply and practically.

20.
J Med Virol ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940906

RESUMO

Pangolin metagenomic data obtained from public databases were used to assemble partial or complete viral genomes showing genetic relationship to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sendai virus, flavivirus, picornavirus, parvovirus, and genomovirus, respectively. Most of these virus genomes showed genomic recombination signals. Phylogeny based on the SARS-CoV-2-related virus sequences assembled in this study and those recently published indicated that pangolin SARS-CoV-2-related viruses were clustered into two sub-lineages according to geographic sampling sites. These findings suggest the need for further pangolin samples, from different countries, to be collected and analyzed for coronavirus to elucidate whether pangolins are intermittent hosts for SARS-CoV-2.

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