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1.
Talanta ; 206: 120177, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514882

RESUMO

Two highly selective OFF-ON isomer fluorescent probes (1 and 2) for homo-/cysteine were designed and synthesized. The pyrene modified tetraphenylethylene derivative with AIE was used as luminescent group while maleimide was used as recognition group. These two isomer probes were found to be nearly nonfluorescent when treated with GSH. However, upon interaction with Cys or Hcy, the fluorescence was enhanced by 2000 folds in a wide pH range from 3 to 10. Experimental results and DFT calculation have demonstrated that the fluorescence OFF-ON switch of such thiol probes is resulted from the termination of the PET (photo-induced electron transfer) effect through the Michael addition reaction of maleimide unit and thiols. In addition, probe 1 and 2 exhibit excellent selectivity and sensitivity towards Cys, Hcy over GSH and other amino acids, which was confirmed by mass MS. We suggested that Michael addition reaction of these probes with GSH was prevented because of the stereo-hindrance effect. Furthermore, these two isomer probes were successfully used for imaging biothiols in living H1299 lung cancer cells.

2.
Acta Crystallogr C Struct Chem ; 75(Pt 10): 1344-1352, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589150

RESUMO

A novel modified polyoxometalate, {PMo12O40[Cu(2,2'-bpy)]}[Cu(2,2'-bpy)(en)(H2O)]2 [2,2'-bpy is 2,2'-bipyridyl (C10H8N2) and en is ethylenediamine (C2H8N2)], has been synthesized hydrothermally and structurally characterized by elemental analysis, TG, IR, XPS and single-crystal X-ray diffraction. The structural analysis reveals that the compound contains the reduced Keggin polyanion [PMo12O40]6- as the parent unit, which is monocapped by [Cu(2,2'-bpy)]2+ fragments via four bridging O atoms on an {Mo4O4} pit and bi-supported by two [Cu(2,2'-bpy)(en)(H2O)]2+ coordination cations simultaneously. There exist strong intramolecular π-π stacking between the capping and supporting units, which play a stabilizing role during the crystallization of the compound. Adjacent POM clusters are further aggregated to form a three-dimensional supramolecular network through noncovalent forces, hydrogen bonding and π-π stacking interactions. In addition, the photocatalytic properties were investigated in detail, and the results indicated that the compound can be used as a photocatalyst towards the decomposition of the organic pollutant methylene blue (MB).

3.
Am J Surg Pathol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31567281

RESUMO

Myoepithelial tumors of soft tissue are uncommon neoplasms characterized histologically by spindle to epithelioid cells arranged in cords, nests, and/or reticular pattern with chondromyxoid to hyaline stroma, and genetically by rearrangement involving EWSR1 (among other less common genes) in about half of the cases. The diagnosis often requires immunostaining to confirm myoepithelial differentiation, most importantly the expression of epithelial markers and S100 protein and/or GFAP. However, there are cases wherein the morphology is reminiscent of myoepithelial tumors, while the immunophenotype falls short. Here, we report 2 highly similar myoepithelioma-like tumors arising in the hands of young adults. Both tumors were well-demarcated and composed of alternating cellular areas with palely eosinophilic hyaline stroma and scattered acellular zones of densely eosinophilic collagen deposition. The tumor cells were mainly epithelioid cells and arranged in cords or small nests. Vacuolated cells encircling hyaline matrix globules were focally prominent. A minor component of nonhyaline fibrous nodular areas composed of bland spindle cells and rich vasculature was also observed. Perivascular concentric spindle cell proliferation and perivascular hyalinization were present in some areas. The tumor cells were positive for CD34 and epithelial membrane antigen (focal) by immunostaining, while largely negative for cytokeratin, S100, GFAP, p63, GLUT1, and claudin-1. By RNA sequencing, a novel OGT-FOXO3 fusion gene was identified in case 1 and confirmed by reverse transcription polymerase chain reaction and fluorescence in situ hybridization in both cases. Sharing the unusual clinicopathologic features and the novel fusion, these 2 cases probably represent a distinct tumor entity, whose relationship with myoepithelial tumors and tumorigenic mechanisms exerted by the OGT-FOXO3 fusion remain to be studied.

4.
Am J Surg Pathol ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31592798

RESUMO

Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma, characterized by a distinctive epithelioid phenotype in a densely sclerotic collagenous stroma, that shows frequent MUC4 immunoreactivity and recurrent gene fusions, often involving EWSR1 gene. A pathogenetic link with low-grade fibromyxoid sarcoma (LGFMS) has been suggested, due to cases with hybrid morphology as well as overlapping genetic signature. However, a small subset of SEF is negative for MUC4 and lacks the canonical EWSR1/FUS gene rearrangements. Triggered by the identification of recurrent YAP1-KMT2A gene fusions by RNA sequencing in 3 index cases of MUC4-negative, EWSR1/FUS fusion-negative SEF, we further investigated a cohort of 14 similar SEF cases (MUC4-negative, EWSR1/FUS fusion-negative) by fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction, and/or DNA-based massively parallel sequencing (MSK-IMPACT) for abnormalities in these genes. Three additional SEFs with KMT2A gene rearrangements and one additional case with YAP1 gene rearrangements were identified by FISH. In addition, one case with YAP1-KMT2A and one with KMT2A-YAP1 fusion were detected by reverse transcription-polymerase chain reaction and MSK-IMPACT, respectively. As a control group, 24 fibromyxoid spindle cell tumors, diagnosed or suspected as fusion-negative LGFMS, were also tested for YAP1 and KMT2A abnormalities by FISH, but none were positive. The YAP1/KMT2A-rearranged SEF group affected patients ranging from 10 to 86 years old (average and median: 45) of both sexes (4 females, 5 males). The tumors involved somatic soft tissues with a wide distribution, including extremities, trunk, neck, and dura. Histologically, the tumors showed variable cellularity, with monotonous ovoid to epithelioid tumor cells and hyalinized collagenous background typical of SEF. More than half of the cases showed infiltrative borders, within fat or skeletal muscle. No LGFMS component was identified. All tumors were negative for MUC4 and had an otherwise nonspecific immunophenotype. Of the 6 cases with available follow-up information, 2 had local recurrences, and 2 developed soft tissue and/or bone metastases, including 1 of them died of the disease.

5.
Nat Cell Biol ; 21(9): 1152-1163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31481791

RESUMO

Ca2+/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase family, and its δ isoform is predominant in the heart. Excessive CaMKII activation plays a pivotal role in the pathogenesis of severe heart conditions, including myocardial infarction, cardiomyopathy and heart failure. However, the identity of CaMKII splice variants and the mechanism(s) underlying CaMKII-mediated cardiac pathology remain elusive. Here, we show that CaMKII-δ9, the most abundant CaMKII-δ splice variant in human heart, potently promotes cardiomyocyte death, cardiomyopathy and heart failure by disrupting cardiomyocyte genome stability. Mechanistically, CaMKII-δ9, but not the previously well-studied CaMKII-δ2 and CaMKII-δ3, targets the ubiquitin-conjugating enzyme E2T (UBE2T) for phosphorylation and degradation, disrupting UBE2T-dependent DNA repair and leading to the accumulation of DNA damage and genome instability. These findings not only reveal a crucial role of CaMKII in the regulation of DNA repair, but also mark the CaMKII-δ9-UBE2T-DNA damage pathway as an important therapeutic target for cardiomyopathy and heart failure.

6.
Small ; : e1901014, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478613

RESUMO

Exosomes are endosome-derived vesicles enriched in body fluids such as urine, blood, and saliva. So far, they have been recognized as potential biomarkers for cancer diagnostics. However, the present single-variate analysis of exosomes has greatly limited the accuracy and specificity of diagnoses. Besides, most diagnostic approaches focus on bulk analysis using lots of exosomes and tend to be less accurate because they are vulnerable to impure extraction and concentration differences of exosomes. To address these challenges, a quantitative analysis platform is developed to implement a sequential quantification analysis of multiple exosomal surface biomarkers at the single-exosome level, which utilizes DNA-PAINT and a machine learning algorithm to automatically analyze the results. As a proof of concept, the profiling of four exosomal surface biomarkers (HER2, GPC-1, EpCAM, EGFR) is developed to identify exosomes from cancer-derived blood samples. Then, this technique is further applied to detect pancreatic cancer and breast cancer from unknown samples with 100% accuracy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31494541

RESUMO

Despite successful clinical applications, teleoperated robotic surgical systems face particular limitations in the functional endoscopic sinus surgery (FESS) in terms of incompatible instrument dimensions and robot set-up. The endoscope remains manually handled by an assistant when the surgeon performs bimanual operations. This paper introduces the development of the Foot-controlled Robot-Enabled EnDOscope Manipulator (FREEDOM) designed for FESS. The system features clinical considerations that inform the design for providing reliable and safe endoscope positioning with minimal obstruction to the routine practice. The robot structure is modular and compact to ensure coaxial instrument manipulation through the nostril for manual procedures. To alter rigid endoscope motions, a new compliant endoscope holder is proposed that passively limits the lens-tissue contact force under collision for patient-side protection. To facilitate hands-free endoscope manipulation that imposes minimal distractions to the surgeon, a foot-wearable interface is further designed to relieve the assistant's workload. The foot control method owns a short learning curve (mean 3.4 mins), and leads the task to be more ergonomic and surgeon-centered. Cadaver and clinical studies were both conducted to evaluate the surgical applicability of the FREEDOM to assist endoscope manipulation in FESS. The system was validated to be safe (IEC-60601-1) and easy for set up (mean 3.6 mins), from which the surgeon could perform various three-handed procedures alone in FESS without disrupting the routine practice.

8.
Int J Biol Macromol ; 141: 41-50, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476391

RESUMO

In this study, the reaction conditions of sulfur trioxide-pyridine (SO3-Pyr) method for the modification of Qingke ß-glucans (THB) were optimized by response surface methodology, and effects of different degrees of substitution (low, medium, and high) on the physicochemical properties, antioxidant activities, and in vitro hypolipidemic activities of THB were investigated. The optimal reaction conditions to obtain the high degree of substitution of sulfated ß-glucans were as follows: ratio of SO3-Pyr to THB of 16.88 g/g, reaction time of 2.03 h, and reaction temperature of 57.54 °C. Results showed that sulfated modification significantly affected the water solubilities, apparent viscosities, molecular weights, and molar ratios of constituent monosaccharides of THB. Besides, the sulfated THB exhibited much better antioxidant activities (DPPH and nitric oxide radical scavenging activities, and reducing powers), in vitro binding properties (fat, cholesterol, and bile-acid binding capacities), and pancreatic lipase inhibition activities than that of THB. Indeed, the sulfated THB with higher degree of substitution has stronger antioxidant activities and in vitro hypolipidemic activities. Results suggested that the sulfated modification could be an efficient approach for the improvement of functional properties of THB, and sulfated THB could be further explored as functional food ingredients for industrial applications.

9.
Iran J Allergy Asthma Immunol ; 18(3): 251-261, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522432

RESUMO

Growing evidence indicated conflicting results that Interleukin-18 (IL-18) promoter polymorphisms rs1946518 (A-607C), rs187238 (G-137C) and rs549908 (A-105C) were associated with asthma risk. The aim of this study is to comprehensively evaluate the IL-18 polymorphisms and asthma by a systematic review and meta-analysis. A total of 12 studies testing the association between these polymorphisms and asthma were examined (8 studies for A-607C, 8 studies for G-137C, and 4 studies for A-105C) in the update meta-analysis, up to Dec 30, 2017. Summary odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the strength of association between each polymorphism and asthma using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. The meta-analysis results indicated that any allele frequencies of the IL-18 polymorphisms (A-607C, G-137C and A-105C) was not associated with asthma risk (p>0.05). And no statistically significant association was observed between genotype frequencies of these polymorphisms and asthma under different genetic models (p>0.05). Subgroup analysis results were similar to the main analysis by ethnicity, sample size, genotyping methods, matching criteria and quality score. There was no evidence of publication bias. The present meta-analysis suggests that IL-18 polymorphisms (A-607C, G-137C and A-105C) were unlikely to be associated with asthma risk.

10.
BMC Genomics ; 20(1): 707, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510913

RESUMO

BACKGROUND: Eggshell breaking strength is critical to reduce egg breaking rate and avoid economic loss. The process of eggshell calcification initiates with the egg entering the uterus and lasts about 18 h. It follows a temporal sequence corresponding to the initiation, growth and termination periods of shell calcification. During each period of shell calcification, our study investigated the differences of gonadal hormones and uterine transcriptome in laying hens producing a high or low breaking strength shell. RESULTS: 60 Hy-line Brown laying hens were selected and divided into two groups according to eggshell breaking strength. Eggshell breaking strength of 44.57 ± 0.91 N and 26.68 ± 0.38 N were considered to be the high strength group (HS) and low strength group (LS), respectively. The results showed that mammillary thickness and mammillary knob width of eggshells were significantly lower in the HS. Serum progesterone (P4) and 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3] were significantly higher in the HS compared to the LS during the initiation period of calcification. Serum estradiol (E2) and calcium did not change significantly. All factors mentioned above had no significant differences in the growth and termination periods of calcification. The relative expression of CaBP-D28k and PMCA 1b were not significantly different between HS and LS. The relative expression of NCX1 was significantly higher in HS compared to LS. Moreover, 1777 differentially expressed genes (DEGs) were obtained in the initiation period of calcification. However, few DEGs were identified in the growth or termination periods of calcification. 30 DEGs were selected as candidate genes involved in eggshell calcification during the initiation period of calcification by the analysis of GO terms and KEGG pathways. CONCLUSIONS: Our study concluded that mammillary thickness and mammillary knob width of the HS were significantly lower than LS. P4 and 1,25-(OH)2D3 were significantly higher in the initiation period of HS. They may impact initial calcification when the mammillary layer is formed. The initiation period of calcification determined eggshell strength rather than the growth or termination periods. We inferred P4 or 1,25-(OH)2D3 may effect the ultrastructure of the mammillary layer by regulating the expression of uterine genes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31518508

RESUMO

The aim of the present study is to explore the effect of retinoic acid (RA) on cardiac injury induced by gestational diabetes mellitus (GDM). GDM mice were given 3 mg/kg RA once daily until the 19th day of pregnancy or the 7th day of postpartum. Compared to normal control and normal pregnant control mice, GDM mice before and after delivery showed significantly cardiac injury. RA treatment attenuated cardiac injury as evidenced by decreased heart weight and left ventricular mass, mRNA expressions of ANP and BNP and cardiac fibrosis compared with that in GDM mice. The protective effect of RA on GDM cardiomyopathy was related with the decreased MDA content and ROS generation, the increased GSH-Px and SOD content, as well as the reduced TNF-α and IL-1ß content and inhibition of NF-κB signaling. In addition, RA treatment delayed the continuous rise of blood glucose before delivery, and decreased the higher level of glucose after delivery. In conclusion, RA treatment could increase the activity of the antioxidant enzyme, suppress the oxidative stress, inflammation response and activation of NF-κB signaling, thereby improving blood glucose level and cardiac injury of GDM mice before and after delivery.

12.
J Environ Sci (China) ; 85: 94-106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471036

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO2 NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO2 NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (AL) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO2 NPs stock suspensions. The cytotoxicity of fresh TiO2 NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO2 NPs. Both Fresh and aged TiO2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ0) AL cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO2 NPs during the aging process. Taken together, our data indicated that TiO2 NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO2 NPs disposal before entering the environment.


Assuntos
Nanopartículas/toxicidade , Titânio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Dano ao DNA , Humanos , Testes de Toxicidade
13.
J Cell Mol Med ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490024

RESUMO

MicroRNA (miRNA) critically controls gene expression in many biological processes, including lung growth and pulmonary surfactant biosynthesis. The present study was conducted to investigate whether miR-20a-5p had such regulatory functions on alveolar type II (AT-II) cells. To accomplish this, miR-20a-5p-overexpressed and miR-20a-5p-inhibited adenoviral vectors were constructed and transfected into cultured AT-II cells that were isolated from rat foetal lungs of 19 days' gestation. Transfection efficiency was confirmed by observing the fluorescence of green fluorescent protein (GFP) carried by the viral vector, whereas miR-20a-5p levels were verified by real-time PCR. The CCK-8 assay was used to compare the proliferation ability of AT-II cells that had over- or underexpressed miR-20a-5p. The expression of surfactant-associated proteins (SPs) and phosphatase and tensin homolog (PTEN) was measured by real-time PCR and Western blotting. In AT-II cells, transfection resulted in over- or under-regulation of miR-20a-5p. While overexpression of miR-20a-5p promoted pulmonary surfactant gene expression, its underexpression inhibited it. Consistent with its role in negatively regulating the pulmonary surfactant gene, an opposite pattern was observed for miR-20a-5p regulation of PTEN. As a result, when miR-20a-5p was rendered overexpressed, PTEN was down-regulated. By contrast, when miR-20a-5p was underexpressed, PTEN was up-regulated. Neither overexpression nor underexpression of miR-20a-5p altered the cell proliferation. miR-20a-5p plays no role in proliferation of foetal AT-II cells but is a critical regulator of surfactant gene expression. The latter appears to be achieved through a regulatory process that implicates expression of PTEN.

14.
ACS Nano ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31490650

RESUMO

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

15.
Math Biosci Eng ; 16(5): 4399-4414, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31499668

RESUMO

Releasing mosquitoes with Wolbachia into the wild mosquito population is becoming the very promising strategy to control mosquito-borne infections. To investigate the effects of wind and critical patch size on the Wolbachia establishment in the wild mosquito population, in this paper, we propose a diffusion-reaction-advection system in a heterogeneous environment. By studying the related eigenvalue problems, we derive various conditions under which Wolbachia can fully establish in the entire wild mosquito population. Our findings may provide some useful insights on designing practical releasing strategies to control the mosquito population.

16.
J Inorg Biochem ; 201: 110822, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31536949

RESUMO

Cisplatin and its analogs have been used for the treatment of various cancers, but their serious side effect has limited clinical application. Presently, scientists are developing other metal drugs as an alternative of cisplatin. In this paper, three new iridium(III) complexes [Ir(ppy)2(adppz)](PF6) (adppz = 7-aminodipyrido[3,2-a:2',3'-c]phenazine; ppy = 2-phenylpyridine 1), [Ir(bzq)2(adppz)](PF6) (bzq = benzo[h]quinolone 2) and [Ir(piq)2(adppz)](PF6) (piq = 1-phenylisoquinoline 3) were synthesized and characterized. The complexes can effectively inhibit the cell colonies. The cytotoxicity in vitro of the complexes against A549, HepG2, SGC-7901, BEL-7402 and normal NIH3T3 cells was evaluated by 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) methods. The intracellular reactive oxygen species (ROS) levels and Ca2+ concentrations were assayed. The mitochondrial membrane potential, a release of cytochrome c and the expression of B-cell lymphoma/leukemia-2 (Bcl-2) family protein have been investigated. The data reveal that the complexes 1-3 can effectively inhibit the cell proliferation in A549 cells with low IC50 value of 3.2 ±â€¯0.4 µM, 4.8 ±â€¯0.5 µM and 1.2 ±â€¯0.2 µM, respectively. The antitumor in vivo shows that complex 3 can inhibit tumor growth with an inhibitory rate of 76.34%. The studies on the mechanism indicate that these complexes cause apoptosis in A549 cell via a ROS-mediated lysosomal-mitochondrial dysfunction pathway. In addition, the interaction of the complexes with BSA was explored.

17.
Mar Drugs ; 17(10)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561527

RESUMO

Marine-derived fungi of the genera Aspergillus could produce novel compounds with significant bioactivities. Among these fungi, the strain Aspergillus flavus is notorious for its mutagenic mycotoxins production. However, some minor components with certain toxicities from A. flavus have not been specifically surveyed and might have potent biological activities. Our investigation of the marine-derived fungus Aspergillus flavus CF13-11 cultured in solid medium led to the isolation of four C-6'/C-7' epimeric drimane sesquiterpene esters, asperienes A-D (1-4). Their absolute configurations were assigned by electronic circular dichroism (ECD) and Snatzke's methods. This is the first time that two pairs of C-6'/C-7' epimeric drimane sesquiterpene esters have successfully been separated. Aperienes A-D (1-4) displayed potent bioactivities towards four cell lines with the IC50 values ranging from 1.4 to 8.3 µM. Interestingly, compounds 1 and 4 exhibited lower toxicities than 2 and 3 toward normal GES-1 cells, indicating more potential for development as an antitumor agent in the future.

18.
Ophthalmology ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31561879

RESUMO

PURPOSE: To develop and validate a deep learning (DL) algorithm that predicts referable glaucomatous optic neuropathy (GON) and optic nerve head (ONH) features from color fundus images, to determine the relative importance of these features in referral decisions by glaucoma specialists (GSs) and the algorithm, and to compare the performance of the algorithm with eye care providers. DESIGN: Development and validation of an algorithm. PARTICIPANTS: Fundus images from screening programs, studies, and a glaucoma clinic. METHODS: A DL algorithm was trained using a retrospective dataset of 86 618 images, assessed for glaucomatous ONH features and referable GON (defined as ONH appearance worrisome enough to justify referral for comprehensive examination) by 43 graders. The algorithm was validated using 3 datasets: dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of GSs; dataset B (9642 images, 1 image/patient; 9.2% referable), images from a diabetic teleretinal screening program; and dataset C (346 images, 1 image/patient; 81.7% referable), images from a glaucoma clinic. MAIN OUTCOME MEASURES: The algorithm was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for referable GON and glaucomatous ONH features. RESULTS: The algorithm's AUC for referable GON was 0.945 (95% confidence interval [CI], 0.929-0.960) in dataset A, 0.855 (95% CI, 0.841-0.870) in dataset B, and 0.881 (95% CI, 0.838-0.918) in dataset C. Algorithm AUCs ranged between 0.661 and 0.973 for glaucomatous ONH features. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders (including 1 GS), while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels. CONCLUSIONS: A DL algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.

19.
Aging (Albany NY) ; 11(17): 7021-7035, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494646

RESUMO

Aging is associated with an increased risk of cardiovascular disease. Numerical and functional declines in endothelial progenitor cells (EPCs) limit their capacity for endothelial repair and promote the development of cardiovascular disease. We explored the effects of nuclear factor (erythroid-derived 2)-like 2 (NRF2) on EPC activity during aging. Both in vitro and in vivo, the biological functioning of EPCs decreased with aging. The expression of NRF2 and its target genes (Ho-1, Nqo-1 and Trx) also declined with aging, while Nod-like receptor protein 3 (NLRP3) expression increased. Aging was associated with oxidative stress, as evidenced by increased reactive oxygen species and malondialdehyde levels and reduced superoxide dismutase activity. Nrf2 silencing impaired the functioning of EPCs and induced oxidative stress in EPCs from young mice. On the other hand, NRF2 activation in EPCs from aged mice protected these cells against oxidative stress, ameliorated their biological dysfunction and downregulated the NLRP3 inflammasome. These findings suggest NRF2 can prevent the functional damage of EPCs and downregulate the NLRP3 inflammasome through NF-κB signaling.

20.
Sci Rep ; 9(1): 13251, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519990

RESUMO

Few neuroimaigng studies on reading comprehension have been conducted under natural reading settings. In this study, we showed texts presented in a natural way during functional MRI (fMRI) measurements to reveal brain areas sensitive to reading comprehension. Specifically, this paradigm independently manipulated two holistic features of article style: text genre and translation style, a qualitative index of how typical word choices and arrangements are made in daily use of the language. Specifically, articles from The New York Times (news) and Reader's Digest (fiction) translated from English to Mandarin Chinese either by human experts or machine (Google Translate) were used to investigate the correlation of brain activity across participants during article reading. We found that bi-hemispheric visual cortex, precuneus, and occipito-parietal junction show significantly correlated hemodynamics across participants regardless of translation style and article genre. Compared to machine translation, reading human expert translation elicited more reliable fMRI signals across participants at precuneus, potentially because narrative representations and contents can be coherently presented over tens of seconds. We also found significantly stronger inter-subject correlated fMRI signals at temporal poles and fusiform gyri in fiction reading than in news reading. This may be attributed to more stable empathy processing across participants in fiction reading. The degree of stability of brain responses across subjects at extra-linguistic areas was found correlated with subjective rating on the text fluency. The functional connectivity between these areas was modulated by text genre and translation style. Taken together, our imaging results suggested stable and selective neural substrates associated with comprehending holistic features of written narratives.

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