RESUMO
In this research, SCAPS-1D simulation software (Version: 3.3.10) was employed to enhance the efficiency of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells. By fine-tuning essential parameters like the work function of the conductive glass, the back contact point, defect density, and the thickness of the light absorption layer, we effectively simulated the optimal performance of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells under identical conditions. The effects of different X-site elements on the overall performance of the device were also explored. The theoretical photoelectric conversion efficiency of the device gradually increases with the successive substitution of halogen elements (Cl, Br, I), reaching 6.09%, 17.02%, and 26.74%, respectively. This trend is primarily attributed to the increasing size of the halogen atoms, which leads to better light absorption and charge transport properties, with iodine (I) yielding the highest theoretical conversion efficiency. These findings suggest that optimizing the halogen element in CsSnX3 can significantly enhance device performance, providing valuable theoretical guidance for the development of high-efficiency all-inorganic perovskite solar cells.
RESUMO
OBJECTIVE: To three-dimensionally (3D) analyze the maxillary morphology of infants with unilateral cleft lip and palate (UCLP) and preliminarily classify the alveolar arch to assist in personalization of sequence therapy. DESIGN: Retrospective study. SETTING: Patients with UCLP referred to outpatients' clinic. PARTICIPANTS: 84 nonsyndromic infants with complete UCLP were recruited (58 boys, 26 girls, mean age 29.48 days). MAIN OUTCOME MEASURE: Morphometric analysis was conducted on 3D maxillary models. Principal component analysis (PCA) and cluster analysis were combined to classify maxillary phenotypes preliminarily. The Wilcoxon Signed Rank test and the Kruskal-Wallis test were used to compare differences between variables. A P value less than .05 was considered statistically significant. RESULTS: The maxilla was divided into three types: narrow, homogenous and broad, accounting for 9.52%, 23.81% and 66.67% respectively. The alveolar cleft site (median value) was located in 61% of the total length of the alveolar arch. In the comparison of anterior and total alveolar lengths, the non-cleft side had longer alveolar bone than the affected side, a difference of approximately 2â mm. Pairwise comparisons of variables describing alveolar symmetry revealed significant differences in all subjects; whereas type C had poorer arch symmetry than types A and B, mainly in terms of anterior and overall symmetry. CONCLUSIONS: In infants with UCLP, the maxillary alveolar arch was inherently asymmetrical with partially bone missing (about 2â mm). Significant differences in alveolar bone morphology and symmetry exist between different types of infants, with individuals with broad clefts (type C, the largest proportion) having the worst maxillary development.
RESUMO
A polymer separator plays a pivotal role in battery safety, overall electrochemical performance, and cell assembly process. Traditional separators are separately produced from the electrodes and dominated by porous polyolefin thin films. In spite of their commercial success, today's separators are facing growing challenges with the increasing demand on the device safety and performance. As an attempt to address this urgent need, here, we propose a concept of in situ separator technology by manipulating the two-dimensional (2D) microfluid nanophase separation (2D-MFPS) of a poly(vinylidene difluoride)/lithium salt solution during drying. Particularly, nanophase separation is effectively regulated by low humidity, salt type, and compositions. For application studies, this 2D-MFPS is directly performed onto commercial electrodes under drying conditions with low humidity to fabricate a high-performance in situ separator with thickness and porous structures comparable to those of commercial Celgard separators. This in situ separator shows superior performance in high-temperature stability and wetting capability to a variety of liquid electrolytes. Finally, pouch cells with this in situ separator technology are successfully assembled with an extremely simplified separator-stacking-free process and demonstrate stable cycle performance due to the well-controlled porous structures and electrode-separator interface.
RESUMO
Osteoblastic bone metastases are commonly detected in patients with advanced prostate cancer (PCa) and are associated with an increased mortality rate. Dickkopf-1 (DKK-1) antagonizes canonical WNT/ß-catenin signaling and plays a complex role in bone metastases. We explored the function of cancer cell-specific DKK-1 in PCa growth, metastasis, and cancer-bone interactions using the osteoblastic canine PCa cell line, Probasco. Probasco or Probasco + DKK-1 (cells transduced with human DKK-1) were injected into the tibia or left cardiac ventricle of athymic nude mice. Bone metastases were detected by bioluminescent imaging in vivo and evaluated by micro-computed tomography and histopathology. Cancer cell proliferation, migration, gene/protein expression, and their impact on primary murine osteoblasts and osteoclasts, were evaluated in vitro. DKK-1 increased cancer growth and stimulated cell migration independent of canonical WNT signaling. Enhanced cancer progression by DKK-1 was associated with increased cell proliferation, up-regulation of NF-kB/p65 signaling, inhibition of caspase-dependent apoptosis by down-regulation of non-canonical WNT/JNK signaling, and increased expression of epithelial-to-mesenchymal transition genes. In addition, DKK-1 attenuated the osteoblastic activity of Probasco cells, and bone metastases had decreased cancer-induced intramedullary woven bone formation. Decreased bone formation might be due to the inhibition of osteoblast differentiation and stimulation of osteoclast activity through a decrease in the OPG/RANKL ratio in the bone microenvironment. The present study indicated that the cancer-promoting role of DKK-1 in PCa bone metastases was associated with increased growth of bone metastases, reduced bone induction, and altered signaling through the canonical WNT-independent pathway. DKK-1 could be a promising therapeutic target for PCa.
Assuntos
Neoplasias Ósseas , Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias da Próstata , Animais , Cães , Humanos , Masculino , Camundongos , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Microambiente Tumoral , Via de Sinalização Wnt , Microtomografia por Raio-XRESUMO
OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: â¢Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. â¢Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. â¢The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates.
RESUMO
The usage of weakly bonded ultra-high strength (WBUHS) rebars has emerged as a promising approach to enhance the resilience of concrete components due to their remarkable mechanical properties. To promote the application of WBUHS rebars, this paper presented an investigation on the seismic behavior of circular concrete columns reinforced with squarely arranged WBUHS rebars and externally confined by bolted steel tubes. Eight columns, including two reinforced with normal strength (NS) rebars and six reinforced with WBUHS rebars, were fabricated and tested under reversed cyclic lateral loading. Experimental results showed that the columns reinforced with WBUHS rebars exhibited remarkable drift-hardening capacity up to the drift of at least 5% as well as significantly reduced residual deformation even when subjected to relatively high axial compression with an axial load ratio of 0.33 in comparison to the traditional ductile columns reinforced with NS rebars. Notably, the precast columns reinforced with WBUHS rebars, with an embedment length of 20 times their diameter, behaved nearly identically in terms of resilience as cast-in-place columns. Additionally, a numerical analysis was performed to assess the hysteretic performance, and the analytical results, with consideration for the slippage of WBUHS rebars, were capable of capturing the hysteretic performance of test columns.
RESUMO
Pilotis structures consisting of upper concrete bearing-walls and a soft first story have been well used in residential and office buildings in urban areas to primarily accommodate parking lots. In this research, drift-hardening concrete (DHC) columns developed by the authors are proposed to form the pilotis story with the aims of reducing its excessive residual drift caused by stronger earthquakes than anticipated in current seismic codes, mitigating damage degree, and enhancing resilience of the pilotis story. Nonlinear dynamic analysis was conducted to investigate the dynamic response characteristics of the wall structures supported by DHC columns. To this end, two sample six-story one-bay pilotis structures were designed following the current Japanese seismic design codes and analyzed. One sample structure is supported by ductile concrete (DC) columns, while the other is supported by DHC columns, which have the same dimensions, steel amount, and concrete strength as DC columns. Three representative ground motions were adopted for the nonlinear dynamic analysis. The analytical parameter was the amplitude of peak ground acceleration (PGA), scaled by the peak ground velocity (PGV) ranging between 12.5 cm/s and 100 cm/s with an interval of 12.5 cm/s. The analytical results have revealed that the residual drift of the pilotis story composed of DHC columns could be reduced to nearly zero under selected earthquakes scaled up to PGV = 100 cm/s, owing to not only the inherent self-centering ability of DHC columns but also the shake-down effect, which implies that the use of DHC columns can greatly enhance resilience of pilotis structures under strong earthquake inputs and promote its application in the buildings located in strong earthquake-prone regions. The maximum inter-story shear forces (MISFs) along the building height of the two models are also compared.
RESUMO
As a member of cyclic nucleotide phosphodiesterase (PDE) enzyme family, PDE10A is in charge of the degradation of cyclic adenosine (cAMP) and guanosine monophosphates (cGMP). While PDE10A is primarily expressed in the medium spiny neurons of the striatum, it has been implicated in a variety of neurological disorders. Indeed, inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system (CNS) pathologies caused by dysfunction of the basal ganglia-of which the striatum constitutes the largest component. A PDE10A-targeted positron emission tomography (PET) radioligand would enable a better assessment of the pathophysiologic role of PDE10A, as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate, thus accelerating the development of effective PDE10A inhibitors. In this study, we designed and synthesized a novel 18F-aryl PDE10A PET radioligand, codenamed [18F]P10A-1910 ([18F]9), in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination. [18F]9 possessed good in vitro binding affinity (IC50 = 2.1 nmol/L) and selectivity towards PDE10A. Further, [18F]9 exhibited reasonable lipophilicity (logD = 3.50) and brain permeability (P app > 10 × 10-6 cm/s in MDCK-MDR1 cells). PET imaging studies of [18F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer kinetics. Preclinical studies in rodents revealed an improved plasma and brain stability of [18F]9 when compared to the current reference standard for PDE10A-targeted PET, [18F]MNI659. Further, dose-response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of [18F]9 for evaluating target occupancy in vivo in higher species. In conclusion, our results indicated that [18F]9 is a promising PDE10A PET radioligand for clinical translation.
RESUMO
BACKGROUND: Gyrovirus homsa1 (GyH1) (also known as Gyrovirus 3, GyV3) is a non-enveloped, small, single-stranded DNA virus, which was first identified in children with acute diarrhea, and was subsequently detected in marketed chickens, broilers with transmissible viral proventriculitis (TVP), and mammals. GyH1 is a pathogenic virus in chickens, causing aplastic anemia, immunosuppression, and multisystem damage. However, the seroepidemiology of GyH1 infection in chickens remains unclear. Here, we investigated the seroprevalence of GyH1 in chickens by ELISA to reveal the endemic status of GyH1 in China. RESULTS: An indirect ELISA with high sensitivity and specificity was developed for investigation of seroepidemiology of GyH1 in chickens in China. The seropositive rate of GyH1 ranged from 0.6% to 7.7% in thirteen provinces, and ranged from 4.1% to 8.1% in eight species chickens. The seropositive rate of GyH1 in broiler breeders was significantly higher than that of in layers. There was a negative correlation between seropositive rate and age of chickens. The highest and lowest seropositive rate were present in chickens at 30-60 days and over 180 days, respectively. CONCLUSIONS: The seroepidemiological investigation results demonstrated that natural GyH1 infection is widespread in chickens in China. Different species showed different susceptibility for GyH1. Aged chickens showed obvious age-resistance to GyH1. GyH1 has shown a high risk to the poultry industry and should be highly concerned.
Assuntos
Gyrovirus , Doenças das Aves Domésticas , Animais , Galinhas , China/epidemiologia , Gyrovirus/genética , Mamíferos , Aves Domésticas , Estudos SoroepidemiológicosRESUMO
The cerebral cortex undergoes rapid microstructural changes throughout the third trimester. Recently, there has been growing interest on imaging features that represent cyto/myeloarchitecture underlying intracortical myelination, cortical gray matter (GM), and its adjacent superficial whitematter (sWM). Using 92 magnetic resonance imaging scans from 78 preterm neonates, the current study used combined T1-weighted/T2-weighted (T1w/T2w) intensity ratio and diffusion tensor imaging (DTI) measurements, including fractional anisotropy (FA) and mean diffusivity (MD), to characterize the developing cyto/myeloarchitectural architecture. DTI metrics showed a linear trajectory: FA decreased in GM but increased in sWM with time; and MD decreased in both GM and sWM. Conversely, T1w/T2w measurements showed a distinctive parabolic trajectory, revealing additional cyto/myeloarchitectural signature inferred. Furthermore, the spatiotemporal courses were regionally heterogeneous: central, ventral, and temporal regions of GM and sWM exhibited faster T1w/T2w changes; anterior sWM areas exhibited faster FA increases; and central and cingulate areas in GM and sWM exhibited faster MD decreases. These results may explain cyto/myeloarchitectural processes, including dendritic arborization, synaptogenesis, glial proliferation, and radial glial cell organization and apoptosis. Finally, T1w/T2w values were significantly associated with 1-year language and cognitive outcome scores, while MD significantly decreased with intraventricular hemorrhage.
Assuntos
Substância Branca , Recém-Nascido , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Cinzenta/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/diagnóstico por imagem , EncéfaloRESUMO
Gyrovirus 3 (GyV3), the third novel emerging species of the genus Gyrovirus of the Anelloviridae family, has been described in multiple hosts. Epidemiologically, there are suggestions that GyV3 is associated with diarrhea/proventriculitis, however, no direct causal evidence exists between GyV3 infection and specific clinical diseases. Herein, we infected special pathogen-free (SPF) chickens with GyV3, and then assessed the pathogenicity and tissue tropism. The results revealed that GyV3 induced persistent infection characterized by diarrhea, aplastic anemia, immunosuppression, and persistent systemic lymphocytic inflammation. Clinically, the infected chickens presented ruffled feathers, diarrhea, anemia, and weight loss. Aplastic anemia was characterized by progressive depletion of hematopoietic cells in the bone marrow, immunosuppression was associated with atrophy of the thymus, spleen, and bursa of Fabricious, progressive lymphocytic inflammations were characterized by proventriculitis, adrenalitis, pancreatitis, hepatitis, nephritis, and bronchitis. Viral loads of GyV3 in tissues exhibited "M", "N", "W" or "V" type dynamic changes. The highest level of viral loads was reported in bone marrow at 7dpi, followed by the adrenal gland at 2 dpi, the sciatic nerve at 7 dpi, and bile at 35 dpi. The bone marrow and kidney demonstrate the strongest immunostaining of GyV3-VP1 antigen and were suggested as the target tissues of GyV3. Collectively, GyV3 is an immunosuppressive pathogenic virus that targets the bone marrow and kidney in chickens. Exploring the pathogenicity and tissue tropism of GyV3 will guide the basic understanding of the biology of GyV3 and its pathogenesis in chickens.
Assuntos
Galinhas , Infecções por Circoviridae/veterinária , Gyrovirus/fisiologia , Gyrovirus/patogenicidade , Doenças das Aves Domésticas/virologia , Tropismo Viral , Anemia Aplástica/imunologia , Anemia Aplástica/veterinária , Anemia Aplástica/virologia , Animais , Infecções por Circoviridae/virologia , Diarreia/imunologia , Diarreia/veterinária , Diarreia/virologia , Tolerância Imunológica , Inflamação/imunologia , Inflamação/veterinária , Inflamação/virologia , Cinética , Linfócitos/imunologia , VirulênciaRESUMO
Gyrovirus 3 (GyV3) has been identified in humans and other hosts, suggesting its cross-species pathogenicity, which poses an increased public health risk. In the current study, we established chicken and mouse models of GyV3 infection. We found that GyV3 induced persistent infections, characterized by viremia, aplastic anemia, immunosuppression, and systematic lymphocytic inflammation, in both species. Kinetic viral loads and antigen expression demonstrated rapid viral replication and broad tissue tropism of GyV3 in both models. The highest viral loads and the strongest antigen immunostaining were present in bone marrow and cerebrum in both chickens and mice, indicating that these are target tissues for GyV3. Genetic diversity analysis of VP1 in infected chickens and mice showed that GyV3 adapts to new hosts via rapid evolution of the hypervariable region of the gene encoding the structural protein VP1. Overall, our results indicate that GyV3 is a cross-species pathogenic virus; therefore, more attention needs to be paid to high levels of GyV3-induced neurotropism and aplastic anemia as a public health risk.
Assuntos
Infecções por Circoviridae/virologia , Gyrovirus/patogenicidade , Especificidade de Hospedeiro , Anemia Aplástica/etiologia , Anemia Aplástica/virologia , Animais , Antígenos Virais/imunologia , Proteínas do Capsídeo/genética , Galinhas , Infecções por Circoviridae/complicações , Modelos Animais de Doenças , Variação Genética , Gyrovirus/genética , Camundongos , Carga ViralRESUMO
The human brain grows the most dramatically during the perinatal and early post-natal periods, during which pre-term birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal magnetic resonance imaging (MRI) pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the cerebrospinal fluid (CSF)/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 pre-term and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532 ± 0.035 mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with post-menstrual age (PMA) at scan (p < 0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3 mm at 28 weeks of PMA to 1.8 mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.
RESUMO
OBJECTIVE: This study aimed to determine the correlations between the craniofacial morphology and pharyngeal airway volume in patients with complete bilateral cleft lip and palate (BCLP). DESIGN: Retrospective study. SETTING: Tertiary hospital. PARTICIPANTS: Twenty-seven patients with complete BCLP and 27 class I control patients, aged 10 to 14 years. MAIN OUTCOME MEASURE: The pharyngeal airway volume and craniofacial morphology were evaluated using cone-beam computed tomography. Measurements were compared between groups and any correlations were identified. RESULTS: A significantly smaller total pharyngeal airway volume (TPV), oropharyngeal airway volume, and upper (UOPV) and lower (LOPV) oropharyngeal airway volume were found in patients with BCLP than in class I control patients, with no difference in the nasopharyngeal volume between groups. Furthermore, the craniofacial morphology measurements of N-Me, S-Go, Or-C, Ptm-C, Me-C, Co-Go, Go-Me, Ptm-Or, N-S-Ar, and Ar-Go-Me significantly differed between the BCLP and control groups (all P < .05). Multiple regression analysis indicated that Ptm-C and Me-C; Ptm-C, Or-C, and Me-C; and Me-C explained 20.3%, 38.9%, and 17.1% of the variations in TPV (P = .025), UOPV (P = .002), and LOPV (P = .018), respectively. CONCLUSIONS: Total pharyngeal airway volume, TPV, OPV, UOPV, and LOPV were significantly smaller in patients with BCLP than in class I controls. In patients with BCLP, the maxilla showed inhibited sagittal development and a retrograde position; moreover, the pharyngeal airway volume was weakly associated with the position of the maxilla and mandible relative to the coronal plane.
Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Cefalometria , Criança , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila/diagnóstico por imagem , Faringe/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Presurgical nasoalveolar molding (NAM) is the most common preoperative treatment for cleft lip and palate. However, NAM may have some limitations such as requiring high technical sensitivity and frequent visits. To simplify the device, some scholars have changed the traditional NAM into a split-NAM consisting of a alveolar molding plate and a nasal hook. This study compared the shaping effect of split NAM and traditional NAM on nasolabial soft tissue using three-dimensional (3D) measurement. METHODS: A total of 39 patients with unilateral cleft lip and palate (UCLP) were enrolled and divided into 2 groups. 13 patients were treated with split-NAM while the other 26 patients were treated with traditional NAM. 3D images of all patients' craniofacial soft tissue before and after NAM treatment were recorded and measured by three-dimensional software. Statistical analysis of measurements in both groups was performed using SPSS software. RESULTS: After treatment, nasal soft tissue symmetry in the split-NAM group was better improved than that in the NAM group in vertical and anterior-posterior direction, but was worse improved in transverse direction. There was no significant difference in labial soft tissue symmetry between two groups. CONCLUSIONS: The split NAM can better elevate the alar and nostrils of the cleft side, and have a better forward effect on alar outer edge, nasal base, and nostrils. However, the traditional NAM can better reduce the width of nasal base.
Assuntos
Fenda Labial/cirurgia , Moldagem Nasoalveolar , Criança , Fissura Palatina/cirurgia , Humanos , Imageamento Tridimensional , Nariz/cirurgia , Procedimentos de Cirurgia Plástica , ContençõesRESUMO
BACKGROUND: Osteoblastic bone metastasis represents the most common complication in men with prostate cancer (PCa). During progression and bone metastasis, PCa cells acquire properties similar to bone cells in a phenomenon called osteomimicry, which promotes their ability to metastasize, proliferate, and survive in the bone microenvironment. The mechanism of osteomimicry resulting in osteoblastic bone metastasis is unclear. METHODS: We developed and characterized a novel canine prostatic cancer cell line (LuMa) that will be useful to investigate the relationship between osteoblastic bone metastasis and osteomimicry in PCa. The LuMa cell line was established from a primary prostate carcinoma of a 13-year old mixed breed castrated male dog. Cell proliferation and gene expression of LuMa were measured and compared to three other canine prostatic cancer cell lines (Probasco, Ace-1, and Leo) in vitro. The effect of LuMa cells on calvaria and murine preosteoblastic (MC3T3-E1) cells was measured by quantitative reverse-transcription polymerase chain reaction and alkaline phosphatase assay. LuMa cells were transduced with luciferase for monitoring in vivo tumor growth and metastasis using different inoculation routes (subcutaneous, intratibial [IT], and intracardiac [IC]). Xenograft tumors and metastases were evaluated using radiography and histopathology. RESULTS: After left ventricular injection, LuMa cells metastasized to bone, brain, and adrenal glands. IT injections induced tumors with intramedullary new bone formation. LuMa cells had the highest messenger RNA levels of osteomimicry genes (RUNX2, RANKL, and Osteopontin [OPN]), CD44, E-cadherin, and MYOF compared to Ace-1, Probasco, and Leo cells. LuMa cells induced growth in calvaria defects and modulated gene expression in MC3T3-E1 cells. CONCLUSIONS: LuMa is a novel canine PCa cell line with osteomimicry and stemness properties. LuMa cells induced osteoblastic bone formation in vitro and in vivo. LuMa PCa cells will serve as an excellent model for studying the mechanisms of osteomimicry and osteoblastic bone and brain metastasis in prostate cancer.
Assuntos
Neoplasias Ósseas/secundário , Linhagem Celular Tumoral/patologia , Osteoblastos/patologia , Neoplasias da Próstata/patologia , Células 3T3 , Animais , Neoplasias Ósseas/genética , Diferenciação Celular/fisiologia , Processos de Crescimento Celular/fisiologia , Cães , Xenoenxertos , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/genética , Células Tumorais CultivadasRESUMO
Circoviruses are found in many species, including mammals, birds, lower vertebrates and invertebrates. To date, there are no reports of circovirus-induced diseases in chickens. In this study, we identified a new strain of chicken circovirus (CCV) by PacBio third-generation sequencing samples from chickens with acute gastroenteritis in a Shandong commercial broiler farm in China. The complete genome of CCV was verified by inverse PCR. Genomic analysis revealed that CCV codes two inverse open reading frames (ORFs), and a potential stem-loop structure was present at the 5' end with a structure typical of a circular virus. Phylogenetic tree analysis showed that CCV formed an independent branch between mammalian and avian circovirus, and homology analysis indicated that the homology of CCV with 21 other known circoviruses was less than 40%. Thus, this CCV strain represents a new species in the genus Circovirus. The infection rate of CCV in 12 chickens with diarrhoea was 100%, but no CCV was found in healthy chickens, thereby indicating that the novel CCV strain is highly associated with acute infectious gastroenteritis in chickens. The emergence of a novel CCV in commercial broiler chickens is highly concerning for the broiler industry.
Assuntos
Galinhas/virologia , Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Diarreia/veterinária , Gastroenterite/veterinária , Genoma Viral/genética , Doenças das Aves Domésticas/virologia , Doença Aguda , Animais , China/epidemiologia , Infecções por Circoviridae/mortalidade , Infecções por Circoviridae/virologia , Circovirus/classificação , Circovirus/genética , Diarreia/mortalidade , Diarreia/virologia , Fezes/virologia , Gastroenterite/mortalidade , Gastroenterite/virologia , Fases de Leitura Aberta/genética , Filogenia , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/mortalidadeRESUMO
The lifecycle of avian leukosis virus subgroup J (ALV-J), a typical tumorigenic retrovirus, is highly dependent upon host cellular proteins. However, there have been few studies directed at uncovering the host proteins responsible for ALV-J replication, which could provide insights into new strategies for ALV-J prevention and control. Here, we used proteomics to identify the association of differential levels of collagen triple helix-repeat-containing 1 (CTHRC1) and with viral replication. Our results revealed that CTHRC1 was significantly upregulated in ALV-J-infected cells in vitro, and these findings were confirmed in vivo. Additionally, CTHRC1 overexpression facilitated ALV-J replication, whereas CTHRC1 knockdown suppressed this activity. Moreover, we found that ALV-J drove CTHRC1 translocation from the nucleus to the cytosol through interactions with the ALV-J envelope glycoprotein. These results revealed CTHRC1 as a shutting protein is recruited by ALV-J to facilitate viral replication.
Assuntos
Vírus da Leucose Aviária/fisiologia , Proteínas da Matriz Extracelular/genética , Interações entre Hospedeiro e Microrganismos , Proteínas do Envelope Viral/genética , Replicação Viral , Animais , Linhagem Celular , Embrião de Galinha , Galinhas/virologia , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/virologia , Proteômica , Proteínas do Envelope Viral/metabolismoAssuntos
Doenças dos Bovinos/microbiologia , Infecções por Enterobacteriaceae/veterinária , Morganella morganii/isolamento & purificação , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/patologia , China/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/patologia , Feminino , Morganella morganii/classificação , Morganella morganii/genéticaRESUMO
Gyrovirus 3 (GyV3) has been identified in faeces from children with acute gastroenteritis. However, whether GyV3 is prevalent in poultry has not been determined to date. To the best of our knowledge, this study is the first to isolate GyV3 from commercial broiler chickens with transmissible viral proventriculitis (TVP) in China. The complete genome of the virus shares 98.4% sequence identity with the FecGy strain that causes acute gastroenteritis in children. Epidemiological investigation from 2013 to 2017 revealed that the infection rate of GyV3 reached 12.5% (42/336) in commercial broiler chickens with TVP, indicating that the infection of GyV3 was ubiquitous in chickens. The emergence of GyV3 in commercial broiler chickens should be highly concerning for public health.