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1.
Sheng Li Xue Bao ; 76(1): 97-104, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38444135

RESUMO

Autophagy is a metabolic process in which damaged organelles, obsolete proteins, excess cytoplasmic components, and even pathogens are presented to lysosomes for degradation via autophagosomes. It includes 4 processes: the initiation of autophagy, the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the degradation and removal of autophagic substrates within autophagic lysosomes. When these processes are continuous, it is called autophagy flux. Blockage of one or certain steps in the autophagy/lysosome signaling pathway can lead to impaired autophagy flux. Numerous studies have shown that impaired autophagy flux is an important cause of neuronal damage in the ischemic penumbra after stroke. This paper summarized research progress in the pathological mechanisms that cause impaired neuronal autophagy flux after ischemic stroke and discusses methods to improve neuronal autophagy flux, in order to provide a reference for an in-depth investigation of the pathological injury mechanisms after stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Autofagia , Lisossomos , Cognição
2.
Org Biomol Chem ; 21(41): 8364-8371, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37815482

RESUMO

A Ce(III)-catalyzed, visible-light induced aerobic oxidative dehydrogenative coupling reaction between glycine derivatives and electron-rich arenes is disclosed. The protocol proceeds efficiently under mild conditions, providing an efficient method for the rapid synthesis of α-arylglycine derivatives without the need for an external photosensitizer and additional oxidant. Moreover, this protocol could be performed on a 5 mmol scale, without obvious reduction of the efficiency.

3.
Cell ; 186(19): 4074-4084.e11, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37669665

RESUMO

H3N8 avian influenza viruses (AIVs) in China caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs and could be vulnerable to infection at epidemic or pandemic proportion.


Assuntos
Vírus da Influenza A Subtipo H3N8 , Influenza Humana , Animais , Humanos , Camundongos , Galinhas , Furões , Vírus da Influenza A Subtipo H3N2 , Aerossóis e Gotículas Respiratórios
4.
Langmuir ; 39(38): 13441-13448, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37657482

RESUMO

Titanium and its alloys have become the most excellent structure materials for naval seawater pipelines due to their high strength and good corrosion resistance. However, marine biofouling poses a serious threat to titanium alloy piping systems because of their good biocompatibility. Recently, the biomimetic antifouling coating, a novel antifouling method, has received great attention. Here, based on this biomimetic idea, we develop a nontoxic antifouling slippery surface (AFSS) using silicone oil, silane coupling agent, nanosilica, nanoceramic coating, epoxy resin, and capsaicin. The developed AFSS has excellent slippery performance for various droplets, good durability, and a superior self-cleaning property. Additionally, the antifouling performance of the AFSS was significantly enhanced, as confirmed by the reduced adhesion of proteins (70.7%), bacteria (97.2%), and algae (97.7%) compared to the ordinary titanium alloy. With these excellent properties, the AFSS was expected to be a promising candidate for protecting titanium alloy piping systems from marine biofouling.

5.
Langmuir ; 39(30): 10593-10600, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37486199

RESUMO

Irregularly shaped electrosurgical devices face significant challenges in electrosurgery due to serious blood and tissue adhesion. Superhydrophobic surfaces inspired by lotus leaves have attracted great attention for their promising antiadhesion properties. However, there are few methods for efficiently preparing superhydrophobic irregularly shaped bipolar electrocoagulation tweezers (BETs). Herein, we propose a simple and environmentally friendly method to fabricate antiadhesion superhydrophobic surfaces on BETs. The superhydrophobicity is obtained by combining laser texturing to form rough structures and low surface energy modification via stearic acid. The formation mechanism of superhydrophobicity is investigated through analyzing microstructures and chemical compositions by scanning electron microscopy, white-light interferometry, and X-ray photoelectron spectroscopy. The functionalized BET surfaces exhibit excellent water repellency with a contact angle of 159.6°, a roll-off angle of 1°, and a surface energy of 14.3 mJ/m2, possessing excellent antiadhesion properties against blood, chicken breast tissue, and pork tissue. Compared with ordinary BETs, the mass of blood, pork tissue, and chicken breast tissue adhered to the superhydrophobic BET is reduced by 97.70, 70.34, and 75.35%, respectively. Moreover, the superhydrophobic BETs have excellent conductivity and maintain good antiadhesion properties after low-temperature storage for 2 weeks, after being impacted by sand and blood and 30 cycles of tape peeling tests. With outstanding antiadhesion performance, the superhydrophobic BET may have promising application prospects in the electrosurgery field.

6.
Chem Commun (Camb) ; 59(18): 2628-2631, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36762590

RESUMO

A Ce(III)-catalyzed, visible-light-induced aerobic oxidative dehydrogenative coupling/aromatization reaction between glycine derivatives and alkenes has been developed, which provides an efficient approach for the synthesis of quinoline derivatives and post-modification of oligopeptides containing glycine residues under mild conditions without the need for external photosensitizers.

7.
Lancet Microbe ; 3(11): e824-e834, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36115379

RESUMO

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H3N8 , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Humanos , Animais , Pré-Escolar , Influenza Aviária/epidemiologia , Vírus da Influenza A Subtipo H3N8/genética , Influenza Humana/epidemiologia , Filogenia , Estudos Retrospectivos , Galinhas , Aves Domésticas , Patos , Mamíferos
9.
J Healthc Eng ; 2022: 9241835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646298

RESUMO

Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU)-induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. However, gout patients manifest other complications, such as hypertension, diabetes, chronic kidney disease, and hormone intolerance, which limit efficacy of some of these first-line drugs. Therefore, this study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. We analyzed the variations in VAS pain scores of five patients, knowing the time of action and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in the mouse model was evaluated by studies in vivo. In vitro studies, we evaluated the effect of natural ACTH on macrophages and revealed different functions of ACTH and dexamethasone on macrophages in the transcriptional level. In patients with acute gout, natural ACTH can quickly alleviate pain and does not affect the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exerts different effects on the transcription of some related genes. Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone at the transcriptional level.


Assuntos
Artrite Gotosa , Gota , Macrófagos , Hormônio Adrenocorticotrópico/uso terapêutico , Animais , Artrite Gotosa/tratamento farmacológico , Dexametasona , Gota/tratamento farmacológico , Humanos , Hidrocortisona/sangue , Inflamação/tratamento farmacológico , Macrófagos/fisiologia , Camundongos , Ácido Úrico/efeitos adversos
10.
RSC Adv ; 12(24): 15038-15045, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35702427

RESUMO

In this research, a facile one-pot method was used to synthesize gold/poly-3,4-ethylene-dioxythiophene/carbon nanotube (AuNPs/PEDOT/CNTs) composite material. The composite material was investigated by Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). Then the synthesized nanocomposite material was dropped on a bare glassy carbon electrode (GCE) to improve the detection performance of dopamine with a high concentration of ascorbic acid and uric acid. The electrochemical behavior of AuNPs/PEDOT/CNTs/GCE was studied by Cyclic Voltammetry (CV), Differential Pulse Voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under optimum conditions, AuNPs/PEDOT/CNTs/GCE showed a good linear response in the concentration range from 9.14 to 29.704 µM with a detection limit (LOD) and sensitivity of 0.283 µM and 1.557 µA µM-1, respectively. This sensor was applied to detect practical samples with good average recovery. It also exhibited good reproducibility and stability.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35549003

RESUMO

Development of high-performance ionic organic network (ION) adsorbents is of great importance for water remediation. However, the research on IONs is still nascent, especially, the design philosophy regarding contaminant adsorption has rarely been explored. In this contribution, we optimized the adsorption efficiency of IONs by increasing the density of charged sites and improving their accessibility. We first produced a new cationic organic network (CON), CON-LDU4, with a high density of positive sites via synthesis from tetra(4-pyridyl)ethene. Compared to the analogue CON-LDU2 that synthesized from tetra(4-(4-pyridyl)phenyl)ethene, CON-LDU4 exhibited higher efficiency in adsorption of methyl blue, indicating that the higher ionic density results in the higher adsorption efficiency. To further improve the accessibility of the active sites, another new CON material (CON-LDU5) was synthesized by employing a hard template. CON-LDU5 exhibited a larger specific surface area than CON-LDU4, with clearly enhanced adsorption efficiency. Finally, CON-LDU5 was used to capture CrO42- ions in water with fast adsorption kinetics (k2 = 0.0328 g mg-1 min-1) and high adsorption capacity (369 mg g-1).

12.
J Acoust Soc Am ; 151(3): 2238, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35364924

RESUMO

The high-performance and aberration-free broadband acoustic lens holds promise for extensive applications, yet remains challenged. In this work, a scheme is proposed, and the experimental demonstration of a planar acoustic Luneburg lens capable of focusing broadband sound ranging from 1 to 3 kHz (relative bandwidth approaching to 100%) in an aberration-free manner is presented. Concretely, plane sound within the frequency range incident from one side can be concentrated on a same point on the opposite edge of the Luneburg lens. The demanded refractive indexes of the lens are obtained from the component space coil acoustic metamaterials, which can easily manipulate the refractive index by adjusting a structural parameter. The prototype of the proposed Luneburg lens is fabricated by three-dimensional printing technology and experimentally characterized in a two-dimensional acoustic measuring platform. The measured results are consistently in good agreement with those from the numerical simulations. Finally, the proposed Luneburg lens is employed to construct a wide-angle acoustic reflector, which can produce a strong echo propagating in the direction exactly opposite to the incident wave. These results facilitate potential possibilities for developing more acoustic functional devices capable of manipulating broadband sound.

13.
Rheumatology (Oxford) ; 61(9): 3841-3853, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35015844

RESUMO

OBJECTIVE: Interleukin (IL)-37 is a natural suppressor of inflammation. Macrophages play an important role in acute gout flare by dominating the inflammation and spontaneous relief. We have reported that IL-37 could limit runaway inflammation in gout. Here we focus on whether IL-37 inhibits gouty inflammation by altering macrophage functions, and how it does so. METHODS: Macrophage functions were evaluated in terms of phagocytosis, pyroptosis, polarization and metabolism. Phagocytosis and polarization of macrophages were detected by side scattering and double-labelling induced nitrogen monoxide synthase (iNOS)/arginase-1 (Arg-1) using flow cytometry, respectively. Transcription of pyroptosis-related molecules was detected by qPCR. Metabolomics was performed by liquid chromatograph mass spectrometer. Human IL-37 knock-in mice and a model with point mutation (S9A) at mouse Gsk3b locus were created by CRISPR/Cas-mediated genome engineering. MSU was injected into the paws and peritoneal cavity to model acute gout. Vernier calliper was used to measure the thickness of the paws. The mice paws and human synovium tissues or tophi were collected for pathological staining. Peritoneal fluid of mice was used to enrich macrophages to detect polarization. RESULTS: IL-37 promoted non-inflammatory phagocytic activity of macrophages by enhancing phagocytosis of MSU, reducing transcription of pyroptosis-related proteins and release of inflammatory cytokines, protecting mitochondrial function, and mediating metabolic reprogramming in MSU-treated THP-1 cells. These multifaceted roles of IL-37 were partly depended on the mediation of glycogen synthase kinase-3ß (GSK-3ß). CONCLUSIONS: Our study revealed that IL-37 could shape macrophages into a 'silent' non-inflammatory phagocytic fashion. IL-37 may become a potentially valuable treatment option for patients of chronic gout, especially for those with tophi.


Assuntos
Artrite Gotosa , Gota , Animais , Artrite Gotosa/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Gota/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-1 , Macrófagos/metabolismo , Camundongos , Fenótipo , Exacerbação dos Sintomas , Ácido Úrico/metabolismo
14.
Oncoimmunology ; 11(1): 2028962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35096486

RESUMO

To develop a short-term follow-up CT-based radiomics approach to predict response to immunotherapy in advanced non-small-cell lung cancer (NSCLC) and investigate the prognostic value of radiomics features in predicting progression-free survival (PFS) and overall survival (OS). We first retrospectively collected 224 advanced NSCLC patients from two centers, and divided them into a primary cohort and two validation cohorts respectively. Then, we processed CT scans with a series of image preprocessing techniques namely, tumor segmentation, image resampling, feature extraction and normalization. To select the optimal features, we applied the feature ranking with recursive feature elimination method. After resampling the training dataset with a synthetic minority oversampling technique, we applied the support vector machine classifier to build a machine-learning-based classification model to predict response to immunotherapy. Finally, we used Kaplan-Meier (KM) survival analysis method to evaluate prognostic value of rad-score generated by CT-radiomics model. In two validation cohorts, the delta-radiomics model significantly improved the area under receiver operating characteristic curve from 0.64 and 0.52 to 0.82 and 0.87, respectively (P < .05). In sub-group analysis, pre- and delta-radiomics model yielded higher performance for adenocarcinoma (ADC) patients than squamous cell carcinoma (SCC) patients. Through the KM survival analysis, the rad-score of delta-radiomics model had a significant prognostic for PFS and OS in validation cohorts (P < .05). Our results demonstrated that (1) delta-radiomics model could improve the prediction performance, (2) radiomics model performed better on ADC patients than SCC patients, (3) delta-radiomics model had prognostic values in predicting PFS and OS of NSCLC patients.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Seguimentos , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
15.
PNAS Nexus ; 1(3): pgac085, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36741455

RESUMO

Clade 2.3.4.4 avian H5Ny viruses, namely H5N2, H5N6, and H5N8, have exhibited unprecedented intercontinental spread in poultry. Among them, only H5N6 viruses are frequently reported to infect mammals and cause serious human infections. In this study, the genetic and biological characteristics of surface hemagglutinin (HA) from clade 2.3.4.4 H5Ny avian influenza viruses (AIVs) were examined for adaptation in mammalian infection. Phylogenetic analysis identified an amino acid (AA) deletion at position 131 of HA as a distinctive feature of H5N6 virus isolated from human patients. This single AA deletion was found to enhance H5N6 virus replication and pathogenicity in vitro and in mammalian hosts (mice and ferrets) through HA protein acid and thermal stabilization that resulted in reduced pH threshold from pH 5.7 to 5.5 for viral-endosomal membrane fusion. Mass spectrometry and crystal structure revealed that the AA deletion in HA at position 131 introduced an N-linked glycosylation site at 129, which increases compactness between HA monomers, thus stabilizes the trimeric structure. Our findings provide a molecular understanding of how HA protein stabilization promotes cross-species avian H5N6 virus infection to mammalian hosts.

16.
Med Phys ; 49(2): 1097-1107, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34951492

RESUMO

BACKGROUND: Ground glass nodule (GGN) segmentation is one of the important and challenging tasks in diagnosing early-stage lung adenocarcinomas. Manually delineating of 3D GGN in a computed tomography (CT) image is a subjective, laborious, and tedious task, which presents poor repeatability. PURPOSE: To reduce the annotation burden and improve the segmentation performance, this study proposes a 3D deep learning-based volumetric segmentation model to segment the GGN in CT images. METHODS: A total of 379 GGNs were retrospectively collected from the public database, Shanghai Pulmonary Hospital (SHPH), and Fudan University Shanghai Cancer Center (FUSCC). First, a series of image preprocessing techniques involving image resampling, intensity normalization, 3D nodule patch cropping, and data augmentation, were adopted to generate the input images for the deep learning model by using CT scans. Then, a 3D attentional cascaded residual network (ACRU-Net) was proposed to develop the deep learning-based segmentation model by using the residual network and the atrous spatial pyramid pooling module. To improve the model performance, a voxel-based conditional random field (CRF) method was used to optimize the segmentation results. Finally, a balanced cross-entropy and Dice combined loss function was applied to train and build the segmentation model. RESULTS: Testing on SHPH and FUSCC datasets, the proposed method generates the Dice coefficients of 0.721 ± 0.167 and 0.733 ± 0.100, respectively, which are higher than those of 3D residual U-Net and ACRU-Net without CRF optimization. CONCLUSIONS: The results demonstrated that combining 3D ACRU-Net and CRF effectively improved the GGN segmentation performance. The proposed segmentation model may provide a potential tool to help the radiologist in the segmentation and diagnosis of 3D GGN.


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares , China , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
PLoS Pathog ; 17(12): e1010098, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860863

RESUMO

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.


Assuntos
Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/virologia , Influenza Humana/virologia , Vírus Reordenados/genética , Proteínas da Matriz Viral/metabolismo , Zoonoses Virais/virologia , Animais , Galinhas/virologia , Humanos , Vírus da Influenza A/genética , Liberação de Vírus
18.
Cancers (Basel) ; 13(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209366

RESUMO

This study aims to develop a deep neural network (DNN)-based two-stage risk stratification model for early lung adenocarcinomas in CT images, and investigate the performance compared with practicing radiologists. A total of 2393 GGNs were retrospectively collected from 2105 patients in four centers. All the pathologic results of GGNs were obtained from surgically resected specimens. A two-stage deep neural network was developed based on the 3D residual network and atrous convolution module to diagnose benign and malignant GGNs (Task1) and classify between invasive adenocarcinoma (IA) and non-IA for these malignant GGNs (Task2). A multi-reader multi-case observer study with six board-certified radiologists' (average experience 11 years, range 2-28 years) participation was conducted to evaluate the model capability. DNN yielded area under the receiver operating characteristic curve (AUC) values of 0.76 ± 0.03 (95% confidence interval (CI): (0.69, 0.82)) and 0.96 ± 0.02 (95% CI: (0.92, 0.98)) for Task1 and Task2, which were equivalent to or higher than radiologists in the senior group with average AUC values of 0.76 and 0.95, respectively (p > 0.05). With the CT image slice thickness increasing from 1.15 mm ± 0.36 to 1.73 mm ± 0.64, DNN performance decreased 0.08 and 0.22 for the two tasks. The results demonstrated (1) a positive trend between the diagnostic performance and radiologist's experience, (2) the DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution decreased model performance in predicting the risks of GGNs. Once tested prospectively in clinical practice, the DNN could have the potential to assist doctors in precision diagnosis and treatment of early lung adenocarcinoma.

19.
Virology ; 561: 28-35, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34139638

RESUMO

Reassortant Eurasian avian-like (EA) H1N1 virus, possessing 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes, namely G4 genotype, has replaced the G1 genotype EA H1N1 virus (all the genes were of EA origin) and become predominant in swine populations in China. Understanding the pathogenicity of G4 viruses in pigs is of great importance for disease control. Here, we conducted comprehensive analyses of replication and pathogenicity of G4 and G1 EA H1N1 viruses in pigs. G4 virus exhibited enhanced replication, increased duration of virus shedding, and caused more severe respiratory lesions in pigs compared with G1 virus. G4 virus, with viral ribonucleoprotein (vRNP) complex genes of pdm/09 origin, exhibited higher levels of nuclear accumulation and higher polymerase activity, which is essential for improved replication of G4 virus. These findings indicate that G4 virus poses a great threat to both swine industry and public health, and control measures should be urgently implemented.


Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/patogenicidade , Doenças dos Suínos/virologia , Animais , Núcleo Celular/metabolismo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Pulmão/patologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , RNA Polimerase Dependente de RNA/metabolismo , Vírus Reordenados/genética , Vírus Reordenados/fisiologia , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Suínos , Doenças dos Suínos/patologia , Traqueia/patologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Virulência , Replicação Viral , Eliminação de Partículas Virais
20.
Cancer Med ; 10(11): 3655-3673, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33934540

RESUMO

PURPOSE: To analyze the role of six human epididymis protein 4 (HE4)-related mitochondrial ribosomal proteins (MRPs) in ovarian cancer and selected MRPL15, which is most closely related to the tumorigenesis and prognosis of ovarian cancer, for further analyses. METHODS: Using STRING database and MCODE plugin in Cytoscape, six MRPs were identified among genes that are upregulated in response to HE4 overexpression in epithelial ovarian cancer cells. The Cancer Genome Atlas (TCGA) ovarian cancer, GTEX, Oncomine, and TISIDB were used to analyze the expression of the six MRPs. The prognostic impact and genetic variation of these six MRPs in ovarian cancer were evaluated using Kaplan-Meier Plotter and cBioPortal, respectively. MRPL15 was selected for immunohistochemistry and GEO verification. TCGA ovarian cancer data, gene set enrichment analysis, and Enrichr were used to explore the mechanism of MRPL15 in ovarian cancer. Finally, the relationship between MRPL15 expression and immune subtype, tumor-infiltrating lymphocytes, and immune regulatory factors was analyzed using TCGA ovarian cancer data and TISIDB. RESULTS: Six MRPs (MRPL10, MRPL15, MRPL36, MRPL39, MRPS16, and MRPS31) related to HE4 in ovarian cancer were selected. MRPL15 was highly expressed and amplified in ovarian cancer and was related to the poor prognosis of patients. Mechanism analysis indicated that MRPL15 plays a role in ovarian cancer through pathways such as the cell cycle, DNA repair, and mTOR 1 signaling. High expression of MRPL15 in ovarian cancer may be associated with its amplification and hypomethylation. Additionally, MRPL15 showed the lowest expression in C3 ovarian cancer and was correlated with proliferation of CD8+ T cells and dendritic cells as well as TGFßR1 and IDO1 expression. CONCLUSION: MRPL15 may be a prognostic indicator and therapeutic target for ovarian cancer. Because of its close correlation with HE4, this study provides insights into the mechanism of HE4 in ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/citologia , Carcinoma Epitelial do Ovário/química , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Proliferação de Células/genética , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Proteínas Mitocondriais/análise , Proteínas Mitocondriais/genética , Neoplasias Ovarianas/química , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/química , Ovário/metabolismo , Prognóstico , RNA Mensageiro/análise , Proteínas de Ligação a RNA/análise , Proteínas de Ligação a RNA/genética , Proteínas Ribossômicas/análise , Proteínas Ribossômicas/genética , Regulação para Cima , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/genética , Adulto Jovem
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