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1.
PLoS Pathog ; 17(1): e1008961, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411789

RESUMO

Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within infected tissues during pathogenesis. All members of the Herpesviridae, including VZV, have a conserved core fusion complex composed of glycoproteins, gB, gH and gL. The ectodomain of the primary fusogen, gB, has five domains, DI-V, of which DI contains the fusion loops needed for fusion function. We recently demonstrated that DIV is critical for fusion initiation, which was revealed by a 2.8Å structure of a VZV neutralizing mAb, 93k, bound to gB and mutagenesis of the gB-93k interface. To further assess the mechanism of mAb 93k neutralization, the binding site of a non-neutralizing mAb to gB, SG2, was compared to mAb 93k using single particle cryogenic electron microscopy (cryo-EM). The gB-SG2 interface partially overlapped with that of gB-93k but, unlike mAb 93k, mAb SG2 did not interact with the gB N-terminus, suggesting a potential role for the gB N-terminus in membrane fusion. The gB ectodomain structure in the absence of antibody was defined at near atomic resolution by single particle cryo-EM (3.9Å) of native full-length gB purified from infected cells and by X-ray crystallography (2.4Å) of the transiently expressed ectodomain. Both structures revealed that the VZV gB N-terminus (aa72-114) was flexible based on the absence of visible structures in the cryo-EM or X-ray crystallography data but the presence of gB N-terminal peptides were confirmed by mass spectrometry. Notably, N-terminal residues 109KSQD112 were predicted to form a small α-helix and alanine substitution of these residues abolished cell-cell fusion in a virus-free assay. Importantly, transferring the 109AAAA112 mutation into the VZV genome significantly impaired viral propagation. These data establish a functional role for the gB N-terminus in membrane fusion broadly relevant to the Herpesviridae.

2.
Eur Radiol ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33416977

RESUMO

OBJECTIVES: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. METHODS: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. RESULTS: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. CONCLUSIONS: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging. KEY POINTS: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.

3.
Phytochemistry ; 183: 112651, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33418167

RESUMO

Eleven previously uncharacterized steroids, along with three analogs were isolated from Aglaia lawii leaves. Their structures were definitely characterized by the methods of NMR, MS, IR, ECD and X-ray crystallography study. Among these unreported compounds, 3-epi-dyscusin C, 3-epi-lansisterone E and (Z)-2α-hydroxyaglawone were C-21 pregnane steroids incorporating a highly oxygenated ring A, while others were Δ5-3ß-hydroxy-7-ketosteroids bearing different ring D and C-17 aliphatic chains. All isolates were evaluated for nitric oxide (NO) inhibitory activities. 3-Epi-dyscusin C, 3-epi-lansisterone E, (Z)-2α-hydroxyaglawone and 17(20)E-dyscusin B showed significant anti-inflammatory activities with IC50 values of NO inhibition less than 10 µM (in the range from 4.47 ± 0.36 to 7.67 ± 0.46 µM).

4.
J Int Med Res ; 49(1): 300060520981539, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33430667

RESUMO

OBJECTIVE: The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. METHODS: Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. RESULTS: Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. CONCLUSIONS: This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

5.
Comput Biol Med ; 130: 104209, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33440316

RESUMO

To realize the automatic diagnosis of cervical intraepithelial neoplasia (CIN) cases by preacetic acid test and postacetic acid test colposcopy images, this paper proposes a method of cervical precancerous lesion diagnosis based on multimodal feature changes. First, the preacetic acid test and postacetic acid test colposcopy images were registered based on cross-correlation and projection transformation, and then the cervical region was extracted by the k-means clustering algorithm. Finally, a deep learning network was used to extract features and classify the preacetic acid test and postacetic acid test cervical images after registration. Finally, the proposed method achieves a classification accuracy of 86.3%, a sensitivity of 84.1%, and a specificity of 89.8% in 60 test cases. Experimental results show that this method can make better use of the multimodal features of colposcopy images and has lower requirements for medical staff in the process of data acquisition. It has certain clinical significance in cervical cancer precancerous lesion screening systems.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33420610

RESUMO

PURPOSE: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. METHODS: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. RESULTS: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. CONCLUSION: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.

7.
Int J Legal Med ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33392657

RESUMO

Forensic scholars are paying more attention to postmortem computed tomography (PMCT) and PMCT angiography (PMCTA), which are gradually becoming effective and practical methods in forensic practice. However, few studies have focused on the application of PMCTA to cardiac ventricular puncture-especially of the right ventricle. In this article, we introduce a pulmonary PMCTA approach by right ventricle cardiac puncture and its potential value in fatalities from pulmonary thromboembolism (PTE). The procedure was performed on 11 males and 6 females. PMCT was performed first; then a biopsy core needle was used for percutaneous puncture of the right ventricle under CT guidance. About 400 mL of contrast media was injected at a rate of 50 mL/8 s, followed by CT scanning. Visualization of the pulmonary artery contrast filling was complete in 9 cadavers, and the pulmonary arteries showed significant filling defects in 8 subjects. Unlike in clinical practice, the phenomenon of postmortem coagulation sometimes occurs in the vascular lumina after death. Therefore, the results of these 8 cases can only suggest or be highly suspicious of death from PTE. Then autopsy and histopathological examination confirmed that 4 of the above 8 patients were diagnosed with PTE; the remaining 4 had postmortem clot including chicken fat clot in the pulmonary artery. Pulmonary PMCTA approach is a simple, convenient, and effective method for the visualization of the pulmonary artery, which can be used as an effective auxiliary tool to identify PTE in forensic practice. It will also provide technical support to further investigate PTE imaging characteristics.

8.
Neurosci Res ; 162: 52-62, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31891740

RESUMO

Resveratrol shows ability to eliminate prion replication, but the exact mechanism for prion eradication was not clear yet. Our previous studies demonstrate a downregulation of brain-derived nerve growth factor (BDNF) during prion infection, meanwhile recovery of cerebral nerve growth factor (NGF) level by resveratrol treatment has been reported in other neurodegenerative models. To obtain the possible changes of brain NGF and its upstream regulatory cascade during prion infection and after removal of prion propagation, the levels of NGF and its upstream regulatory factors in various prion-infected and prion-eradicated SMB cell lines and mice brains inoculated with various SMB cellular lysates were assessed with various methodologies. The levels of NGF were significantly decreased during prion replication, while recovered after removal of PrPSc by resveratrol in vitro. Morphological assays revealed that the NGF signals mainly colocalized within neurons, but not in the proliferative astrocytes and microglia. The upstream positive regulatory kinases, such as p-CREB, p-CaMKIV, CaMKK2 were decreased in the prion infected cells and mice brains, whereas the negative regulatory one, p-CaMKK2, was increased. The aberrant situations of those kinases in prion infected cell lines or mice brains could be also partially reversed by removal of prion agent. Moreover, we demonstrated that the signals of CaMKK2 and p-CaMKK2 were also distributed predominately in neurons in the brain tissues. The data illustrate a direct linkage of abnormally repressive NGF and its upstream regulatory kinases with prion infection. Resveratrol has not only the ability to inhibit prion replication, but also to improve the expression of NGF via CaMKK2/CaMKIV cascade, which might benefit the microenvironment in brains.

9.
J Chromatogr A ; 1636: 461782, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33316559

RESUMO

Cytokinins (CKs) are one class of important phytohormones widely investigated in most aspects of plant life. Similar to other phytohormones, CKs and their glycoconjugates are hydrophilic. Their ionization efficiencies for mass spectrometry (MS) detection are rather poor, whereas their retention and separation on reverse phase liquid chromatography (RPLC) are often unsatisfying. Chemical isotope labelling LC-MS analysis methods have been developed for most other phytohormones, enhancing their LC separations and quantitative sensitivity. However, there are currently no reports for chemical-labelled CKs. Here, we report a new chemical isotope labelling LC-MS analytical method for one-pot derivatization of CK bases and their glycoconjugates, based on differential benzylation labelling of the adenine skeleton of CKs with benzyl bromide and its deuterium isotope-labelled reagent. Benzylation alters the hydrophilicity of CKs and their glycoconjugates, improving their retention and separation on RPLC. The developed method demonstrated enhanced sensitivity, as the CKs and their glycoconjugates could be analysed with LODs within the range of 0.62-25.9 pg/mL. The method also demonstrated good intra- and inter-day precisions with standard deviations in the range of 1.9%-13.0%, and acceptable accuracy with recoveries in the range of 84.0%-119.9%. The developed method was employed on the quantitation of CKs in the fresh roots of Astragalus membranaceus collected from both fertilized and unfertilized fields. The significant impact that fertilizers had on endogenous CKs metabolism was observed. As such, monitoring endogenous CKs and their metabolites might be promising to control fertilizer abuse.

10.
Oral Oncol ; 112: 105049, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33221541

RESUMO

INTRODUCTION: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival. METHODS: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes. RESULTS: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729). CONCLUSIONS: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.

11.
J Mater Chem B ; 9(1): 176-186, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33237117

RESUMO

Tough hydrogels with the ability to be repeatedly processed into various shapes as thermoplastics are highly desired in advanced medical devices and tissue engineering. Here, we have developed a kind of versatile supramolecular hydrogel with a network cross-linked by double hydrogen bonds from poly(N-acryloyl glycinamide) (PNAGA). The resulting PNAGA-30 hydrogels (30 wt% solid content) are tough, re-processable, and recyclable similar to thermoplastics. The hydrogels in the form of fragments can be easily re-processed into various shapes including sheet, filament, cylinder and other complex shapes by using simple stamping and injection methods. The mechanical properties of the re-programed hydrogels are comparable to the properties of the original hydrogels. The re-processability and robust mechanical properties of the PNAGA hydrogels are promising for practical applications in soft materials, tissue engineering and wearable devices. Furthermore, the PNAGA-30&LiCl ionic hydrogels can be fabricated by simply compositing LiCl into thermoplastic hydrogels. The PNAGA-30&LiCl hydrogels can function as multifunctional strain sensors to monitor large human movements and tiny vibrations, thereby showing great application potential in robotics, biomedical prosthetics, personal healthcare monitoring and so on.

12.
Medicine (Baltimore) ; 99(49): e23329, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285710

RESUMO

Ovarian cancer is one of the common female malignant tumors. The early diagnosis and treatment of ovarian cancer has been a research hotspot. Therefore, we aimed to investigate the correlations between the levels of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), D-dimer (DDI), and fibrinogen degradation product (FDP) in patients with type II epithelial ovarian cancer.From January 2018 to January 2019, a total of 952 patients who underwent initial surgery for epithelial ovarian cancer were enrolled in this study. Peripheral venous blood was taken before operation, and the levels of CA125, HE4, DDI, and FDP were tested. The correlations between the levels of CA125, HE4, DDI, and FDP and other clinical indicators (such as presence or absence of chemotherapy, surgical conditions) were analyzed.The level of DDI or FDP was statistically associated with age, chemotherapy, Figo staging, surgical procedure, HE4 level, and CA125 level, respectively. Moreover, the Figo staging was statistically correlated with the levels of HE4 and CA125. Besides, we found the levels of CA125 and HE4 were positively correlated with the levels of DDI and FDP.The levels of CA125 and HE4 are the traditional detection indexes for patients with type II epithelial ovarian cancer, and these 2 indicators reflected the degree of disease and prognosis. The levels of DDI and FDP were closely related to the levels of CA125 and HE4 in type II epithelial ovarian cancer, and they also helped to assess the prognosis of epithelial ovarian cancer. Further larger-scale prospective cohort studies are warranted to determine these associations in the future.


Assuntos
Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Antígeno Ca-125/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Adulto Jovem
13.
J Mol Diagn ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33271368

RESUMO

RNA sequencing (RNA-seq) is a well-validated tool for detecting gene fusions in fresh frozen tumors; however, RNA-seq is much more challenging to use with formalin-fixed, paraffin-embedded (FFPE) tumor samples. We evaluated the performance of RNA-seq to detect gene fusions in clinical FFPE tumor samples. Our assay identified all 15 spiked-in NTRK fusions from RNA reference material and six known fusions from five cancer cell lines. Limit of detection for the assay was assessed with a series of dilutions of RNA from the cell line H2228. These fusions can be detected when the dilution is down to 10%. Good intra-assay and interassay reproducibility was observed in three specimens. For clinical validation, the assay detected 10 of 12 fusions initially identified by a DNA panel (covering 23 gene fusions) in clinical specimens (83.3% sensitivity), whereas one fusion (MET fusion) was identified in another 34 fusion-negative tumor specimens as determined by the DNA panel (negative prediction value of 94.3%). This MET fusion was confirmed by RT-PCR and Sanger sequencing, which found that this is a false-negative result for the DNA panel. The assay also identified 26 extra fusions not covered by the DNA panel, 20 (76.9%) of which were validated by RT-PCR and Sanger sequencing. Therefore, this RNA assay has reasonable performance and could complement DNA-based next-generation sequencing assays.

14.
ACS Biomater Sci Eng ; 6(12): 6896-6905, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33320592

RESUMO

In recent years, biomimetic tubular scaffolds have been widely used to repair various human tissue defects, due to their hollow structure similar to the native tissues such as blood vessel, trachea, ureter, and bone marrow cavity. However, there are still many challenges in manufacturing a tubular hydrogel scaffold with suitable mechanical properties, specific microstructure, and good biocompatibility. In this study, we exploited an enzymatic cross-linking method using horseradish peroxidase (HRP) as an enzyme and hydrogen peroxide (H2O2) as a substrate, and combining with gelatin's thermal sensitivity to produce an enzymatically cross-linked silk fibroin/gelatin-tyramine (E-SF/GT) tubular hydrogel. Through further treatment with methanol, we fabricated an EM-SF/GT tubular hydrogel with fine-wall architecture that consists of two different layers (inner and outer, dense and porous). Mechanical measurement showed that the compressive moduli values were up to 4.82 MPa and the tensile moduli values were up to 4.79 kPa under the static loading conditions. Also, degradation test showed that the hydrogel's degradation time was prolonged. Finally, the bioactivity was tested by seeding mouse bone marrow mesenchymal stem cells (mBMSCs) in the lumen of a small-diameter (2 mm) EM-SF/GT tubular hydrogel. Cell morphology and immunofluorescence test indicated that mBMSCs differentiated into endothelial cells and lined the inner surface of the tubular hydrogel under induction. This work provided a feasible strategy for developing tubular hydrogels, which could be potentially used as scaffolds for hollow multilayer tissue engineering, such as blood vessels.

15.
Cell Metab ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33357458

RESUMO

In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.

16.
Clin Appl Thromb Hemost ; 26: 1076029620971041, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33141604

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is an important complication in patients with malignant tumors. Its exact diagnosis and treatment are still lacking. We used a high-sensitive chemiluminescence method to detect thrombin-antithrombin III complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex(t-PAIC) in combination with D-dimer and fibrin degradation product (FDP) to analyze their diagnostic and prognostic value in patients with malignant tumors. METHODS: In total, 870 patients with confirmed malignant tumors were included, 82 of whom had diagnosed VTE; 200 healthy individuals were classified as the control group. The TAT, PIC, TM, and t-PAIC were detected using Sysmex HISCL5000 automated analyzers, whereas FDP and D-dimer were detected using Sysmex CS5100 coagulation analyzer. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency. Survival probabilities were determined using Kaplan-Meier analysis, and multivariate analyses were performed using a Cox regression model. RESULTS: Compared with healthy controls, patients with malignant tumors showed significantly elevated TAT, PIC, TM, t-PAIC, D-dimer, and FDP. Similarly, compared with patients in the non-thrombosis group, those in the thrombosis group showed significantly elevated levels of the above mentioned markers. Logistic regression analysis showed that TAT, PIC, TM, t-PAIC, D-Dimer, and FDP were all associated with VTE. ROC analysis showed that "TAT+PIC+TM+t-PAIC+D-dimer+FDP"showed the highest sensitivity and specificity. Patients with elevated TAT, PIC, TM, and t-PAIC had a significantly shorter survival. Multivariate Cox survival analysis showed that TM and t-PAIC were significantly associated with poor prognosis. In addition, the incidence of VTE was significantly lower in patients with malignant tumors who were treated with low-molecular-weight heparin (LMWH), and their survival period was significantly longer than that of patients with malignant tumors who were not treated with LMWH. CONCLUSION: TAT, PIC, TM, and t-PAIC combined with D-dimer and FDP were better than the application of a single marker in the diagnosis of VTE in patients with malignant tumors. TAT and PIC can be used as sensitive markers in the diagnosis of VTE but not as prognostic markers. TM and t-PAIC might be independent prognostic indicators in patients with malignant tumors, regardless of the state of thrombus.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33175517

RESUMO

Deep-blue emitters are greatly desirable for preparing white light-emitting diodes and enhancing the color gamut of full-color display. The deep-blue lead halide perovskite light-emitting diodes (PeLEDs) exhibit far inferior performance compared to green and red counterparts and suffer from lead toxicity, hampering their applications. Nontoxic, stable, and wide band gap zero-dimensional (0D) Cs3Cu2I5 with relatively high exciton binding energy has great potential as deep-blue emitters. However, the development of PeLEDs remains a huge challenge due to the difficulties in preparing a high-quality Cs3Cu2I5 film and device design, arising from an inherent wide band gap together with deep ionization potential. Here, a continuous and pin-hole-free Cs3Cu2I5 thin film with deep-blue emission centered at 440 nm was prepared by the dual-source thermal evaporation approach, and a high photoluminescence quantum yield of 58% was achieved, corresponding to significant enhancement of 61% compared with that of the Cs3Cu2I5 thin film synthesized by solution processes. Furthermore, saturated deep-blue PeLEDs at the Commission Internationale de L'Eclairage (CIE) coordinates (0.15, 0.08) were obtained by employing an electron-transfer layer composed of a 1,4,5,8,9,11-hexa-azatriphenylene hexacarboni-trile (HAT-CN) and N,N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)benzidine (NPB) organic heterojunction to realize the effective hole blocking, rendering an external quantum efficiency of approximately 0.1%. These results will be extensively beneficial to wide band gap material and device preparation.

18.
J Am Chem Soc ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147413

RESUMO

The halide perovskite Ruddlesden-Popper (RP) phases are a homologous layered subclass of solution-processable semiconductors that have aroused great attention, especially for developing long-term solar photovoltaics. They are defined as (A')2(A)n-1PbnX3n+1 (A' = spacer cation, A = cage cation, and X = halide anion). The orientation control of low-temperature self-assembled thin films is a fundamental issue associated with the ability to control the charge carrier transport perpendicular to the substrate. Here we report new chemical derivatives designed from a molecular perspective using a novel spacer cation 3-phenyl-2-propenammonium (PPA) with conjugated backbone as a low-temperature strategy to assemble more efficient solar cells. First, we solved and refined the crystal structures of single crystals with the general formula (PPA)2(FA0.5MA0.5)n-1PbnI3n+1 (n = 2 and 3, space group C2) using X-ray diffraction and then used the mixed halide (PPA)2(Cs0.05(FA0.88MA0.12)0.95)n-1Pbn(I0.88Br0.12)3n+1 analogues to achieve more efficient devices. While forming the RP phases, multiple hydrogen bonds between PPA and inorganic octahedra reinforce the layered structure. For films we observe that as the targeted layer thickness index increases from n = 2 to n = 4, a less horizontal preferred orientation of the inorganic layers is progressively realized along with an increased presence of high-n or 3D phases, with an improved flow of free charge carriers and vertical to substrate conductivity. Accordingly, we achieve an efficiency of 14.76% for planar p-i-n solar cells using PPA-RP perovskites, which retain 93.8 ± 0.25% efficiency with encapsulation after 600 h at 85 °C and 85% humidity (ISOS-D-3).

19.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158067

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer deaths in the United States. Currently, chemotherapy is a first-line treatment for CRC. However, one major drawback of chemotherapy is the emergence of multidrug resistance (MDR). It has been well-established that the overexpression of the ABCB1 and/or ABCG2 transporters can produce MDR in cancer cells. In this study, we report that in vitro, poziotinib can antagonize both ABCB1- and ABCG2-mediated MDR at 0.1-0.6 µM in the human colon cancer cell lines, SW620/Ad300 and S1-M1-80. Mechanistic studies indicated that poziotinib increases the intracellular accumulation of the ABCB1 transporter substrates, paclitaxel and doxorubicin, and the ABCG2 transporter substrates, mitoxantrone and SN-38, by inhibiting their substrate efflux function. Accumulation assay results suggested that poziotinib binds reversibly to the ABCG2 and ABCB1 transporter. Furthermore, western blot experiments indicated that poziotinib, at 0.6 µM, significantly downregulates the expression of the ABCG2 but not the ABCB1 transporter protein, suggesting that the ABCG2 reversal effect produced by poziotinib is due to transporter downregulation and inhibition of substrate efflux. Poziotinib concentration-dependently stimulated the ATPase activity of both ABCB1 and ABCG2, with EC50 values of 0.02 µM and 0.21 µM, respectively, suggesting that it interacts with the drug-substrate binding site. Molecular docking analysis indicated that poziotinib binds to the ABCB1 (-6.6 kcal/mol) and ABCG2 (-10.1 kcal/mol) drug-substrate binding site. In summary, our novel results show that poziotinib interacts with the ABCB1 and ABCG2 transporter, suggesting that poziotinib may increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC.

20.
Aging (Albany NY) ; 12(20): 20445-20456, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109772

RESUMO

CC-115 is a dual inhibitor of DNA-PKcs and mTOR, both are valuable therapeutic targets for renal cell carcinoma (RCC). Our results showed that CC-115 inhibited survival and proliferation of established RCC cell lines (786-O and A489) and primary human RCC cells. The dual inhibitor induced selective apoptosis activation in RCC cells, as compared to no cytotoxicity nor apoptotic effects toward normal renal epithelial cells. CC-115 inhibited DNA-PKcs and mTORC1/2 activation in RCC cells. It was however ineffective in DNA-PKcs-mTOR double knockout (DKO) 786-O cells. CC-115 induced feedback autophagy activation in RCC cells. Autophagy inhibitors or Beclin-1/Light chain 3 (LC3) silencing potentiated CC-115-induced anti-RCC cell activity. Conversely, ectopic overexpression of Beclin-1 inhibited CC-115-induced cytotoxicity. At last CC-115 oral administration inhibited 786-O subcutaneous xenograft growth in nude mice. Taken together, dual inhibition of DNA-PKcs and mTOR by CC-115 potently inhibited RCC cell growth.

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