ABSTRACT
Inhibitors of complement and coagulation are present in the saliva of a variety of blood-feeding arthropods that transmit parasitic and viral pathogens. Here, we describe the structure and mechanism of action of the sand fly salivary protein lufaxin, which inhibits the formation of the central alternative C3 convertase (C3bBb) and inhibits coagulation factor Xa (fXa). Surface plasmon resonance experiments show that lufaxin stabilizes the binding of serine protease factor B (FB) to C3b but does not detectably bind either C3b or FB alone. The crystal structure of the inhibitor reveals a novel all ß-sheet fold containing 2 domains. A structure of the lufaxin-C3bB complex obtained via cryo-electron microscopy (EM) shows that lufaxin binds via its N-terminal domain at an interface containing elements of both C3b and FB. By occupying this spot, the inhibitor locks FB into a closed conformation in which proteolytic activation of FB by FD cannot occur. C3bB-bound lufaxin binds fXa at a separate site in its C-terminal domain. In the cryo-EM structure of a C3bB-lufaxin-fXa complex, the inhibitor binds to both targets simultaneously, and lufaxin inhibits fXa through substrate-like binding of a C-terminal peptide at the active site as well as other interactions in this region. Lufaxin inhibits complement activation in ex vivo models of atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH) as well as thrombin generation in plasma, providing a rationale for the development of a bispecific inhibitor to treat complement-related diseases in which thrombosis is a prominent manifestation.
Subject(s)
Blood Coagulation , Complement Factor B , Cryoelectron Microscopy , Complement Factor B/chemistry , Complement Factor B/metabolism , Complement Activation , Serine Endopeptidases , Complement C3b/chemistryABSTRACT
Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.
ABSTRACT
The ability to deploy decentralized laboratories with autonomous and reliable disease diagnosis holds the potential to deliver accessible healthcare services for public safety. While microfluidic technologies provide precise manipulation of small fluid volumes with improved assay performance, their limited automation and versatility confine them to laboratories. Herein, we report the utility of multicolor assay-on-a-chip processed by robotic operation (MACpro), to address this unmet need. The MACpro platform comprises a robot-microfluidic interface and an eye-in-hand module that provides flexible yet stable actions to execute tasks in a programmable manner, such as the precise manipulation of the microfluidic chip along with different paths. Notably, MACpro shows improved detection performance by integrating the microbead-based antibody immobilization with enhanced target recognition and multicolor sensing via Cu2+-catalyzed plasmonic etching of gold nanorods for rapid and sensitive analyte quantification. Using interferon-gamma as an example, we demonstrate that MACpro completes a sample-to-answer immunoassay within 30 min and achieves a 10-fold broader dynamic range and a 10-fold lower detection limit compared to standard enzyme-linked immunosorbent assays (0.66 vs 5.2 pg/mL). MACpro extends the applications beyond traditional laboratories and presents an automated solution to expand diagnostic capacity in diverse settings.
Subject(s)
Lab-On-A-Chip Devices , Robotics , Humans , Immunoassay/methods , Interferon-gamma/analysis , Microfluidic Analytical Techniques/instrumentation , Gold/chemistryABSTRACT
The transcatheter edge-to-edge mitral valve repair (TEER) has been recommended as a reliable treatment option for selected patients with severe degenerative and functional mitral regurgitation (MR). Although MR patients with rheumatic etiology were excluded from two significant trials (EVEREST II and COAPT) that established a role for the TEER in degenerative and functional MR. However, it has been reported that the TEER procedure could be safely and effectively performed in carefully selected rheumatic MR patients. Therefore, we share a case report of successfully treating severe rheumatic MR using a novel-designed TEER system (JensClipTM).
Subject(s)
Cardiac Catheterization , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Mitral Valve , Rheumatic Heart Disease , Severity of Illness Index , Humans , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/etiology , Cardiac Catheterization/instrumentation , Treatment Outcome , Rheumatic Heart Disease/diagnostic imaging , Rheumatic Heart Disease/surgery , Rheumatic Heart Disease/physiopathology , Rheumatic Heart Disease/therapy , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve/physiopathology , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Female , Echocardiography, Transesophageal , Echocardiography, Doppler, Color , Prosthesis Design , Heart Valve Prosthesis , Middle Aged , MaleABSTRACT
Topological indices quantify the connectivity and structural properties of chemical compounds. We use the topological indices for predicting and evaluating the numerous properties of molecules, such as boiling temperatures, toxicity, and biological activity. Zagreb connection indices are a useful tool for studying the structural characteristics of the DNA backbone network. These indices provide important information on the arrangement and connections between nucleotide bases inside the DNA molecule. These indices show compactness, complexity, and topological properties in order to predict DNA bending propensity, DNA-protein interaction, and DNA stability. DNA folding patterns and the impact of mutations on DNA networks are areas of further research for these topological indices. In this study, we calculate Zagreb connection indices and modified Zagreb connection indices for backbone DNA network and subdivided backbone DNA network. Furthermore, we compute the hyper-Zagreb connection index, the inverse sum connection index, and the harmonic connection index.
Subject(s)
DNA , Nucleic Acid Conformation , DNA/chemistry , Models, MolecularABSTRACT
Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.
Subject(s)
Actinobacillus Infections , Actinobacillus pleuropneumoniae , Acute Lung Injury , Flavanones , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , NF-kappa B , Animals , Mice , Actinobacillus Infections/veterinary , Actinobacillus Infections/drug therapy , Actinobacillus pleuropneumoniae/drug effects , Acute Lung Injury/drug therapy , Acute Lung Injury/prevention & control , Flavanones/therapeutic use , Flavanones/pharmacology , Heme Oxygenase-1 , Kelch-Like ECH-Associated Protein 1/metabolism , Membrane Proteins , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy. MATERIALS AND METHODS: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as DGH=VDVp3, then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction. The dosimetric parameters of target area and organs at risk in 30 cases before and after re-optimization were compared. RESULTS: On the premise of ensuring that the target dose met the clinical requirements, the trigger factor obtained based on DGF could further reduce the V5, V10, V20, V30 and mean lung dose (MLD) of the ipsilateral lung in breast cancer radiotherapy, Pâ<â0.01. And the D2cc and mean heart dose (MHD) of the heart were also reduced, Pâ<â0.01. Besides, the NTCPs of the ipsilateral lung and the heart were also reduced, Pâ<â0.01. CONCLUSION: The trigger factor obtained based on DGF is efficient in reducing radiation induced lung injury in breast cancer radiotherapy.
Subject(s)
Breast Neoplasms , Lung Injury , Radiation Injuries , Radiotherapy, Intensity-Modulated , Humans , Female , Lung Injury/etiology , Lung Injury/prevention & control , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Breast Neoplasms/radiotherapy , Lung , Radiation Injuries/prevention & controlABSTRACT
BACKGROUND: It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa. METHODS: The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells. RESULTS: Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2highCD69low subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2lowCD69high subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs). CONCLUSION: The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa.
Subject(s)
Breast Neoplasms , Female , Humans , Biomarkers , Breast Neoplasms/genetics , Cell Proliferation , Neoadjuvant Therapy , Oncogenes , Prognosis , Tumor Microenvironment/geneticsABSTRACT
Anthracite is globally used as a filter material for water purification. Herein, it was found that up to 15 disinfection byproducts (DBPs) were formed in the chlorination of anthracite-filtered pure water, while the levels of DBPs were below the detection limit in the chlorination of zeolite-, quartz sand-, and porcelain sandstone-filtered pure water. In new-anthracite-filtered water, the levels of dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and ammonia nitrogen (NH3-N) ranged from 266.3 to 305.4 µg/L, 37 to 61 µg/L, and 8.6 to 17.1 µg/L, respectively. In aged anthracite (collected from a filter at a DWTP after one year of operation) filtered water, the levels of the above substances ranged from 475.1 to 597.5 µg/L, 62.1 to 125.6 µg/L, and 14 to 28.9 µg/L, respectively. Anthracite would release dissolved substances into filtered water, and aged anthracite releases more substances than new anthracite. The released organics were partly (around 5%) composed by the µg/L level of toxic and carcinogenic aromatic carbons including pyridine, paraxylene, benzene, naphthalene, and phenanthrene, while over 95% of the released organics could not be identified. Organic carbon may be torn off from the carbon skeleton structure of anthracite due to hydrodynamic force in the water filtration process.
Subject(s)
Disinfectants , Drinking Water , Water Pollutants, Chemical , Water Purification , Drinking Water/analysis , Drinking Water/chemistry , Disinfection , Chlorine , Coal , Chlorides , Carbon , Halogenation , Water Pollutants, Chemical/analysis , Disinfectants/analysisABSTRACT
BACKGROUND: Deep learning surpasses many traditional methods for many vision tasks, allowing the transformation of hierarchical features into more abstract, high-level features. PURPOSE: To evaluate the prognostic value of preoperative computed tomography (CT) image texture features and deep learning self-learning high-throughput features (SHF) on postoperative overall survival in the treatment of patients with colorectal cancer (CRC). MATERIAL AND METHODS: The dataset consisted of 810 enrolled patients with CRC confirmed from 10 November 2011 to 10 February 2018. In contrast, SHF extracted by deep learning with multi-task training mechanism and texture features were extracted from the CT with tumor volume region of interest, respectively, and combined with the Cox proportional hazard (CoxPH) model for initial validation to obtain a RAD score to classify patients into high- and low-risk groups. The SHF stability was further validated in combination with Neural Multi-Task Logistic Regression (N-MTLR) model. The overall recognition ability and accuracy of CoxPH and N-MTLR model were evaluated by C-index and Integrated Brier Score (IBS). RESULTS: SHF had a more significant degree of differentiation than texture features. The result is (SHF vs. texture features: C-index: 0.884 vs. 0.611; IBS: 0.025 vs. 0.073) in the CoxPH model, and (SHF vs. texture features: C-index: 0.861 vs. 0.630; IBS: 0.024 vs. 0.065) in N-MTLR. CONCLUSION: SHF is superior to texture features and has potential application for the preoperative prediction of the individualized treatment of CRC.
Subject(s)
Colorectal Neoplasms , Deep Learning , Humans , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/surgery , Phenotype , Tomography, X-Ray Computed/methodsABSTRACT
It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. Whole genome bisulfite sequencing (WGBS) is able to generate the sequencing data of DNAs, and shows the potential ability to detect CNVs. However, the evaluations and performances on the detections of CNVs using WGBS data is still unclear. In this study, five software with different strategies for CNV detections, e.g., BreakDancer, cn.mops, CNVnator, DELLY and Pindel, were selected to explore and benchmark the performances of CNV detections with WGBS data. Based on the real (2.62 billion reads) and simulated (12.35 billion reads) WGBS data of humans, we calculated the number, precision, recall, relative ability, memory usage, and running time of CNV detections by 150 times, and tried to figure out the optimal strategy for CNV detections with WGBS data. Based on the real WGBS data, Pindel detected the most deletions and duplications, CNVnator detected the deletions with the highest precision, cn.mops detected the duplications with the highest precision, Pindel detected the deletions with the highest recall, and cn.mops detected the duplications with the highest recall. Based on the simulated WGBS data, BreakDancer detected the most deletions, and cn.mops detected the most duplications. The CNVnator showed the highest precision and recall for both deletions and duplications. In real and simulated WGBS data, the ability of CNVnator to detect CNVs was likely to overtake that in the whole genome sequencing data. Additionally, DELLY and BreakDancer displayed the lowest peak of memory usage and the lest CPU runtime, while CNVnator expressed the highest peak of memory usage and the most CPU runtime. Taken together, CNVnator and cn.mops showed the excellent performances of CNV detections with WGBS data. These results suggested that it was feasible to detect CNVs using WGBS data, and provided the useful information to further investigate both CNVs and DNA methylation using WGBS data alone.
Subject(s)
DNA Copy Number Variations , Genome, Human , Humans , Whole Genome SequencingABSTRACT
Papilio machaon was assigned as the type species for all butterflies by Linnaeus and P. bianor is a congener but exhibits a great difference in morphology (especially larva and adult color pattern) and larval host plants from P. machaon. Thus, they are the ideal models to investigate genetic mechanisms underlying morphology and plasticity between congeners. The reference genomes of both species were dissected in our previous studies, but little is known about their regulatory genome and the epigenetic regulation of gene expression throughout developmental stages. Here, we profiled the chromatin accessibility and gene expression of three developmental stages (the 4th instar larva [L4], the 5th instar larva [L5], and pupa [P]) using transposase accessible chromatin sequencing (ATAC-seq) and RNA-seq. Results showed that many accessible chromatin peaks were identified at three developmental stages (peak number, P. machaon: 44,977 [L4], 36,919 [L5], 47,147 [P]; P. bianor: 20,341 [L4], 44,668 [L5], 62,249 [P]). Moreover, the number of differentially accessible peaks and differentially expressed genes between larval stages of each butterfly species are significantly fewer than that between larval and pupal stages, suggesting a higher similarity within larvae and a significant difference between larvae and pupae. This study added the annotated information of chromatin accessibility genome-wide of the two papilionid species and will promote the investigation of gene regulation in butterfly evolution.
Subject(s)
Butterflies , Animals , Butterflies/genetics , Chromatin/genetics , Epigenesis, Genetic , Larva/genetics , Pupa/geneticsABSTRACT
Geoacoustic inversion using moving sensors attracts lots of interest due to the ease of deployment and low cost. However, the well-established techniques, such as matched-field inversion (MFI), may run into difficulties when the sensors are in a range-dependent environment for mismatch issues and increasing unknown parameters. Given a range-dependent environment, the paper focuses on the inversion using a synthetic aperture created by moving sensors in the presence of the Doppler effect. The derivation is given to obtain an equivalent range-independent environmental model for fast inversion, instead of a range-dependent one. The received fields are modified using the Doppler-shifted wavenumbers. The simulations and results of the SWellEx-96 experimental data verify the effectiveness of the proposed inversion method.
ABSTRACT
Cells respond heterogeneously to molecular and environmental perturbations. Phenotypic heterogeneity, wherein multiple phenotypes coexist in the same conditions, presents challenges when interpreting the observed heterogeneity. Advances in live cell microscopy allow researchers to acquire an unprecedented amount of live cell image data at high spatiotemporal resolutions. Phenotyping cellular dynamics, however, is a nontrivial task and requires machine learning (ML) approaches to discern phenotypic heterogeneity from live cell images. In recent years, ML has proven instrumental in biomedical research, allowing scientists to implement sophisticated computation in which computers learn and effectively perform specific analyses with minimal human instruction or intervention. In this review, we discuss how ML has been recently employed in the study of cell motility and morphodynamics to identify phenotypes from computer vision analysis. We focus on new approaches to extract and learn meaningful spatiotemporal features from complex live cell images for cellular and subcellular phenotyping.
Subject(s)
Cell Movement , Machine Learning , Phenotype , Physiology/methodsABSTRACT
BACKGROUND: Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. METHODS: Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. RESULTS: Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. CONCLUSIONS: We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.
Subject(s)
Colorectal Neoplasms/metabolism , Ferroptosis/drug effects , Hydrogen Sulfide/metabolism , Nanospheres/chemistry , Zinc Oxide , Animals , Glutathione/metabolism , HCT116 Cells , Humans , Mice , Zinc Oxide/chemistry , Zinc Oxide/metabolism , Zinc Oxide/pharmacologyABSTRACT
The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20-22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR-30b-5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin-fixed and paraffin-embedded kidney cancer tissue samples. After cDNA synthesis, real-time quantitative PCR (RT-qPCR) was adopted for detecting the relative miR-30b-5p level. Then, the Kaplan-Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR-30b-5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR-30b-5p expression had remarkably longer overall survival. Thus, the miR-30b-5p level might be related to RCC prognosis.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , MicroRNAs/genetics , Aged , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/pathology , Male , Middle Aged , Prognosis , ROC Curve , Up-RegulationABSTRACT
A high resolution direction-of-arrival (DOA) approach is presented based on deep neural networks (DNNs) for multiple speech sources localization using a small scale array. First, three invariant features from the time-frequency spectrum of the input signal include generalized cross correlation (GCC) coefficients, GCC coefficients in the mel-scaled subband, and the combination of GCC coefficients and logarithmic mel spectrogram. Then the DNN labels are designed to fit the Gaussian distribution, which is similar to the spatial spectrum of the multiple signal classification. Finally, DOAs are predicted by performing peak detection on the DNN outputs, where the maximum values correspond to speech signals of interest. The DNN-based DOA estimation method outperforms the existing high resolution beamforming techniques in numerical simulations. The proposed framework implemented with a four-element microphone array can effectively localize multiple speech sources in an indoor environment.
ABSTRACT
Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/ß-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.
Subject(s)
Adenocarcinoma of Lung/genetics , Cell Movement/genetics , Exosomes/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , A549 Cells , Adenocarcinoma of Lung/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Ceramides/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Lung Neoplasms/pathology , Male , Membrane Proteins/genetics , Middle Aged , Signal Transduction/genetics , Smad4 Protein/geneticsABSTRACT
BACKGROUND: To evaluate the feasibility of using a single device to close multiple atrial septal defects (ASDs) under the guidance of transthoracic echocardiography (TTE) and with the aid of three-dimensional (3D) printing models. METHODS: Sixty-two patients with multiple ASDs were retrospectively analyzed. Thirty of these patients underwent TTE-guided closure (3D printing and TTE group) after a simulation of occlusion in 3D printing models. The remaining 32 patients underwent ASD closure under fluoroscopic guidance (conventional group). Closure status was assessed immediately and at 6 months after device closure. RESULTS: Successful transcatheter closure with a single device was achieved in 26 patients in the 3D printing and TTE group and 27 patients in the conventional group. Gender, age [18.8 ± 15.9 (3-51) years in the 3D printing and TTE group; 14.0 ± 11.6 (3-50) years in the conventional group], mean maximum distance between defects, prevalence of 3 atrial defects and large defect distance (defined as distance ≥7 mm), and occluder size used were similarly distributed between groups. However, the 3D printing and TTE group had lower frequency of occluder replacement (3.8% vs 59.3%, p < 0.0001), prevalence of mild residual shunts (defined as <5 mm) immediately (19.2% vs 44.4%, p < 0.05) and at 6 months (7.7% vs 29.6%, p < 0.05) after the procedure, and cost (32960.8 ± 2018.7 CNY vs 41019.9 ± 13758.2 CNY, p < 0.01). CONCLUSION: The combination of the 3D printing technology and ultrasound-guided interventional procedure provides a reliable new therapeutic approach for multiple ASDs, especially for challenging cases with large defect distance.
Subject(s)
Echocardiography/methods , Heart Septal Defects, Atrial , Printing, Three-Dimensional , Septal Occluder Device , Surgery, Computer-Assisted/methods , Adolescent , Adult , Cardiac Catheterization/methods , Female , Fluoroscopy/methods , Heart Septal Defects, Atrial/diagnosis , Heart Septal Defects, Atrial/surgery , Humans , Male , Outcome and Process Assessment, Health Care , Patient-Specific Modeling , Prosthesis Design , Retrospective StudiesABSTRACT
An organocatalytic domino aza/oxa-Michael/1,6-addition reaction of ortho-tosylaminophenyl or ortho-hydroxyphenyl-substituted para-quinone methides and ynals has been developed. In the presence of 20 mol % of morpholine, this unprecedented cascade reaction occurs readily in good yield (up to 99%), providing a highly efficient synthetic approach to synthetically valuable 1,4-dihydroquinolines and 4H-chromenes.