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Two Gram-stain negative, aerobic and rod-shaped bacterial strains, DHOD12T and 7GSK02T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Strain DHOD12T grew at 4-42â°C (optimum, 28-33â°C), pH 4.0-8.5 (optimum, pH 5.5-6.5) and in the presence of 0-1.5â% (w/v; optimum, 0-0.5â%)NaCl; while strain 7GSK02T grew at 12-42â°C (optimum, 28-33â°C), pH 4.0-8.5 (optimum, pH 5.0-6.0) and in the presence of 0-0.5â% (w/v; optimum, 0â%) NaCl. Strains DHOD12T and 7GSK02T had the highest 16S rRNA sequence similarities of 98.0 and 98.3â% with the same species Trinickia mobilis DHG64T, respectively, and 98.4â% between themselves. In the 16S rRNA phylogeny, they formed a clade that was sister to a major cluster consisting of all described Trinickia species. Phylogenomic analyses with the UBCG and PhyloPhlAn methods consistently showed that strains DHOD12T and 7GSK02T formed a clade with T. mobilis DHG64T that was a sister of a cluster containing the remainder of the Trinickia species. The DNA G+C contents of strains DHOD12T and 7GSK02T were 63.1 and 64.6âmol%, respectively. Digital DNA-DNA hybridization and average nucleotide identity values of strains DHOD12T, 7GSK02T and their closely related strains were in the ranges of 21.6-31.4â% and 77.1-86.9â%, respectively. These two strains had the same major respiratory quinone, ubiquinone-8, and both had C16â:â0, C17â:â0 cyclo and summed feature 8 (C18â:â1 ω7c/C18â:â1 ω6c) as their major fatty acids. Their major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Genomic analysis indicated that the two strains could have the potential to degrade aromatic compounds like other Trinickia species. On the basis of phenotypic and phylogenetic results, strains DHOD12T and 7GSK02T represent two novel species of the genus Trinickia, for which the names Trinickia violacea sp. nov. (type strain DHOD12T=LMG 30258T=CGMCC 1.15436T) and Trinickia terrae sp. nov. (type strain 7GSK02T=CGMCC 1.15432T=KCTC 62468T) are proposed.
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Burkholderiaceae , Ácidos Graxos , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Filogenia , Cloreto de Sódio , DNA Bacteriano/genética , Análise de Sequência de DNA , Composição de Bases , Técnicas de Tipagem Bacteriana , FlorestasRESUMO
The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as ß-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to ß-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation.
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Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Regulação da Expressão Gênica/fisiologia , Cristalino/crescimento & desenvolvimento , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fator de Transcrição Sp1/metabolismo , Sumoilação/fisiologia , Animais , Western Blotting , Imunoprecipitação da Cromatina , Primers do DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Fatores de Crescimento de Fibroblastos/metabolismo , Imuno-Histoquímica , Imunoprecipitação , Cristalino/citologia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This paper presents the preparation of a pyrazoline compound and the properties of its UV-Vis absorption and fluorescence emission. Moreover, this compound can be used to determine Hg(2+) ion with selectivity and sensitivity in the EtOH:H2O =9:1 (v/v) solution. This sensor forms a 1:1 complex with Hg(2+) and shows a fluorescent enhancement with good tolerance of other metal ions. This sensor is very sensitive with fluorometric detection limit of 3.85 × 10(-10) M. In addition, the fluorescent probe has practical application in cells imaging.
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Técnicas Biossensoriais , Corantes Fluorescentes/química , Mercúrio/análise , Pirazóis/química , Estrutura Molecular , Espectrometria de FluorescênciaRESUMO
Quinoa is a nutrient-dense pseudocereal that has garnered global attention for its potential to bolster food security and nutrition. Despite its celebrated status, the detailed nutritional profiles of various quinoa varieties remain poorly understood, which poses a significant barrier to the strategic cultivation and utilization of quinoa's genetic diversity to combat malnutrition. The impetus for this research lies in the urgent need to identify superior quinoa strains that can be tailored to meet specific nutritional requirements and adapt to diverse agro-ecological zones. Our findings reveal substantial variation in nutrient content across different quinoa varieties, highlighting the variety ZLZX-8 as a particularly nutrient-rich strain with the highest levels of protein, fat, essential fatty acids, amino acids, and key minerals such as Mg, K, and Zn. Moreover, ZLZX-8's exceptional antioxidant capacity suggests it may have additional health benefits beyond its macronutrient profile. In contrast, ZLZX-7 stands out for its dietary fiber and phenolic content, which are critical for digestive health and disease prevention, respectively. Meanwhile, ZLZX-5, with its high starch content, could be better suited for energy production in dietary applications. Notably, the study also uncovers a correlation between grain color and nutrient profile, with colored quinoa varieties exhibiting superior fiber, inositol, phenolic content, and antioxidant activity compared to their white counterparts. This work lays the groundwork for an informed selection of quinoa varieties that can enhance dietary quality, support local and global food systems, and contribute to the fight against malnutrition.
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AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.
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Phacoemulsification and intraocular lens implantation is the most effective treatment of cataract.Traditional intraocular lens were mainly monofocal. Postoperative patients can return to a certain distance vision or near vision, but because of the loss of accommodative power, patients must rely on glasses to complete the work of the different distances, the postoperative life there is still a lot of inconvenience. In recent years, the design of multifocal intraocular lens has been the focus of basic and applied research in cataract, but so far the researchers still could not have agreement with the strengths and weaknesses of the multifocal and monofocal intraocular lens. There are three major controversies: First of all, whether it is worth the expense of contrast sensitivity and increased visual disturbance in return for compensatory adjustment? Second, whether it is possible to really get the full range of vision and to get rid of dependence on glasses to use multifocal intraocular lens? Third, how to grasp the indications of multifocal intraocular lens to play to their strengths.
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Lentes Intraoculares , Desenho de Prótese , Sensibilidades de Contraste , Humanos , Acuidade VisualRESUMO
Although long-read single-cell RNA isoform sequencing (scISO-Seq) can reveal alternative RNA splicing in individual cells, it suffers from a low read throughput. Here, we introduce HIT-scISOseq, a method that removes most artifact cDNAs and concatenates multiple cDNAs for PacBio circular consensus sequencing (CCS) to achieve high-throughput and high-accuracy single-cell RNA isoform sequencing. HIT-scISOseq can yield >10 million high-accuracy long-reads in a single PacBio Sequel II SMRT Cell 8M. We also report the development of scISA-Tools that demultiplex HIT-scISOseq concatenated reads into single-cell cDNA reads with >99.99% accuracy and specificity. We apply HIT-scISOseq to characterize the transcriptomes of 3375 corneal limbus cells and reveal cell-type-specific isoform expression in them. HIT-scISOseq is a high-throughput, high-accuracy, technically accessible method and it can accelerate the burgeoning field of long-read single-cell transcriptomics.
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Isoformas de RNA , RNA , Isoformas de RNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Consenso , Isoformas de Proteínas/genética , Análise de Sequência de DNA/métodos , Análise de Sequência de RNARESUMO
AIMS: To evaluate anterior segment optical coherence tomography (AS-OCT) in the diagnosis and treatment of Descemet's membrane detachment (DMD) with severe corneal edema. METHODS: Nine eyes of 7 consecutive patients with suspected DMD with severe corneal edema due to different causes were imaged with the AS-OCT system. Configuration of Descemet's membrane (DM) was delineated before and after treatment, and quantitative analysis was performed. An appropriate treatment was chosen based on the imaging findings. RESULTS: DMD was demonstrated as being present in all eyes via AS-OCT. Different statuses of the DM including planar/nonplanar detachment, local/extensive detachment, and rupture was documented using AS-OCT images. Two eyes were treated with conservative therapy, 6 eyes with intracameral air/gas tamponade and 1 eye with penetrating keratoplasty. One of the air tamponade treatments failed and all the other treatments were successful. CONCLUSION: AS-OCT is a valuable tool in the diagnosis of DMD both in terms of selecting the appropriate treatment, and monitoring treatment outcomes when corneal edema is present.
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Edema da Córnea/diagnóstico , Edema da Córnea/cirurgia , Lâmina Limitante Posterior/patologia , Tomografia de Coerência Óptica , Edema da Córnea/etiologia , Feminino , Humanos , Ceratoplastia Penetrante , Implante de Lente Intraocular , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Facoemulsificação , Complicações Pós-Operatórias , Estudos Prospectivos , Ruptura Espontânea , Acuidade VisualRESUMO
Hemostatic materials are generally applied in surgical operations for cancer, but their effects on the growth and recurrence of tumors are unclear. Herein, three commonly used naturally derived hemostatic materials, gelatin sponge, Surgicel (oxidized regenerated cellulose), and biopaper (mixture of sodium hyaluronate and carboxymethyl chitosan), were cocultured with A549 human lung adenocarcinoma cells in vitro. Furthermore, the performance of hemostatic materials and the tumorigenicity of the materials with A549 âcells were observed after subcutaneous implantation into BALB/c mice. The in vitro results showed that biopaper was dissolved quickly, with the highest cell numbers at 2 and 4 days of culture. Gelatin sponges retained their structure and elicited the least cell infiltration during the 2- to 10-day culture. Surgicel partially dissolved and supported cell growth over time. The in vivo results showed that biopaper degraded rapidly and elicited an acute Th1 lymphocyte reaction at 3 days after implantation, which was decreased at 7 days after implantation. The gelatin sponge resisted degradation and evoked a hybrid M1/M2 macrophage reaction at 7-21 days after implantation, and a protumor M2d subset was confirmed. Surgicel resisted early degradation and caused obvious antitumor M2a macrophage reactions. Mice subjected to subcutaneous implantation of A549 âcells and hemostatic materials in the gelatin sponge group had the largest tumor volumes and the shortest overall survival (OS), while the Surgicel and the biopaper group had the smallest volumes and the longest OS. Therefore, although gelatin sponges exhibited cytotoxicity to A549 âcells in vitro, they promoted the growth of A549 âcells in vivo, which was related to chronic M2d macrophage reaction. Surgicel and biopaper inhibited A549 âcell growth in vivo, which is associated with chronic M2a macrophage reaction or acute Th1 lymphocyte reaction.
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Percutaneous vertebroplasty (PVP) has been used widely to treat pain caused by osteolytic spinal lesions, whereas vertebroplasty for osteoblastic spinal lesions is less known. The purpose of this study is to describe PVP as a highly effective miniinvasive procedure to treat painful osteoblastic metastatic spinal lesions. Four patients with painful osteoblastic metastatic spinal lesions were treated by PVP in the authors' department, and immediately relief of pain was achieved in all of them. The findings from this study may encourage more studies of PVP in palliative treatment of patients with osteoblastic lesions.
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Osteoblastos/patologia , Dor/prevenção & controle , Neoplasias da Coluna Vertebral/terapia , Vertebroplastia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastos/diagnóstico por imagem , Dor/etiologia , Medição da Dor , Cuidados Paliativos , Radiografia Intervencionista , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vertebroplastia/efeitos adversosRESUMO
OBJECTIVE: To compare the amounts of intraocular lens (IOL) decentration and tilt, the anterior chamber depth (ACD) and the degree of posterior capsule opacification (PCO) using the Pentacam Scheimpflug System after cataract surgery between eyes with 1-piece acrylic IOL and 3-piece acrylic IOL. METHODS: It was a perspective study. Fifty-one patients with bilateral senile cataract had implantation of a 1-piece SA60AT IOL in one eye and a 3-piece MA60BM IOL in the contralateral eye. The amount of IOL decentration, tilt, the ACD, and the degree of PCO was measured using the Pentacam Scheimpflug System 1 day and 1, 6, 12 and 24 months postoperatively. RESULTS: There were no significant changes during the 24 m follow-up period in the decentration (0.37 ± 0.16, 0.36 ± 0.15, 0.36 ± 0.16, 0.37 ± 0.15, 0.38 ± 0.16), tilt (3.59 ± 0.91, 3.64 ± 0.92, 3.61 ± 0.90, 3.63 ± 0.90, 3.70 ± 0.89) or PCO (22.20 ± 3.99, 21.96 ± 4.00, 22.40 ± 4.03, 22.53 ± 4.00, 22.95 ± 3.87) in the 1-piece SA60AT group (F = 1.938, 0.785, 1.814; P > 0.05) or in the 3-piece MA60BM group (0.34 ± 0.14, 0.33 ± 0.14, 0.34 ± 0.14, 0.35 ± 0.14, 0.36 ± 0.14), (3.55 ± 0.90, 3.57 ± 0.92, 3.63 ± 0.88, 3.61 ± 0.88, 3.65 ± 0.89), (21.14 ± 3.88, 20.98 ± 3.87, 21.23 ± 3.83, 21.59 ± 3.82, 21.65 ± 3.87) (F = 1.004, 0.525, 1.963; P > 0.05). There was no significant difference between the two groups in IOL decentration (t = 0.802, 0.701, 0.588, 0.898, 0.631), tilt (t = 0.199, 0.337, 0.094, 0.121, 0.248) or PCO (t = 1.214, 1.119, 1.334, 1.082, 1.517) at any time points (P > 0.05). The ACD did not change after the surgery in the 1-piece group (3.90 ± 0.99, 3.88 ± 1.07, 3.91 ± 1.01, 3.90 ± 1.02, 3.92 ± 1.02) (F = 1.333, P > 0.05) but was significantly deeper in the 3-piece group (4.37 ± 1.02, 3.90 ± 0.98, 3.95 ± 0.99, 3.93 ± 0.96, 3.97 ± 0.99) (F = 92.757, P < 0.05) one day after the operation. The ACD was more shallow in the 1-piece SA60AT group than in the 3-piece MA60BM group at all time points. However, the difference was statistically significant only at 1 day after surgery (t = 102.944, P < 0.05). CONCLUSIONS: The degrees of IOL decentration, tilt, ACD and PCO in eyes with a 1-piece acrylic IOL with flexible haptics implanted in the capsular bag were similar to those in eyes with a 3-piece acrylic IOL with rigid PMMA haptics. But the 1-piece acrylic IOL provides a better stability than the 3-piece acrylic IOL in the early stage postoperatively.
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Resinas Acrílicas/uso terapêutico , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do TratamentoRESUMO
Alzheimer's disease (AD) is a fatal neurodegenerative disease for which currently no cure is available. Electroacupuncture (EA) has been widely used in China as an alternative therapeutic approach for neurological diseases. The cognitive decline in patients with AD has been reported to be closely related to the deposition of amyloid-ß (Aß) in the hippocampus of the brain, and the Morris water maze (MWM) test is a widely used method for assessing the behavior of animal models. In this study, the MWM test was performed to evaluate the effects of EA treatment on cognitive function and memory, and the micro-positron emission tomography scan was used to assess the hippocampal Aß deposition. The results showed that the cognitive function of APP/PS1 mice was significantly improved and the rate of [18F]AV-45 uptake was reduced in the EA group, compared with the AD group. Our study suggested that EA can exert a therapeutic effect in AD by improving spatial learning and memory and inhibiting the hippocampal Aß deposition.
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Doença de Alzheimer , Eletroacupuntura , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Eletroacupuntura/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/genéticaRESUMO
AIMS: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH. METHODS: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI. RESULTS: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. CONCLUSIONS: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.
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Lesões Encefálicas/metabolismo , Coenzima A Ligases/biossíntese , Ferroptose/fisiologia , Hemorragia Subaracnóidea/metabolismo , Animais , Lesões Encefálicas/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologiaRESUMO
The homeostasis of the ocular lens is maintained by a microcirculation system propagated through gap junction channels. It is well established that the intercellular communications of the lens become deteriorative during aging. However, the molecular basis for this change in human lenses has not been well defined. Here, we present evidence to show that over 90% of Cx46 and Cx50 are lost in the fiber cells of normal human lenses aged 50 and above. From transparent to cataractous lenses, while Cx43 was upregulated, both Cx46 and Cx50 were significantly down-regulated in the lens epithelia. During aging of mouse lenses, Cx43 remained unchanged, but both Cx46 and Cx50 were significantly downregulated. Under oxidative stress treatment, mouse lenses develop in vitro cataractogenesis. Associated with this process, Cx43 was significantly upregulated, in contrast, Cx46 and Cx50 were sharply downregulated. Together, our results for the first time reveal that downregulation in Cx46 and Cx50 levels appears to be the major reason for the diminished coupling conductance, and the aging-dependent loss of Cx46 and Cx50 promotes senile cataractogenesis.
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Envelhecimento/fisiologia , Catarata/genética , Catarata/patologia , Conexinas/biossíntese , Conexinas/genética , Cristalino/patologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Epitélio Corneano/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-IdadeRESUMO
Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.
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Nanoporos , Análise de Sequência de DNA , Linhagem Celular , Cromossomos Humanos/genética , Genoma Humano , Humanos , Retinoblastoma/genética , SoftwareRESUMO
BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.
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Algoritmos , Simulação por Computador , Aprendizado Profundo , Doenças do Sistema Digestório/diagnóstico , Olho , Programas de Rastreamento/métodos , Modelos Biológicos , Adulto , Área Sob a Curva , China , Túnica Conjuntiva/diagnóstico por imagem , Doenças do Sistema Digestório/complicações , Olho/diagnóstico por imagem , Fundo de Olho , Humanos , Iris/diagnóstico por imagem , Fígado , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Prospectivos , Curva ROC , Esclera/diagnóstico por imagem , Microscopia com Lâmpada de Fenda/métodosRESUMO
OBJECTIVE: To investigate the effect of the ubiquitin-proteasome pathway inhibitor MG132 on the natural resistance to cisplatin in the human cervical cancer line (HCE1) multicellular spheroid (HCE1/MCS) model and to probe it if MG132 could reverse the HCE1/MCS resistance to cisplatin, as well as the possible mechanism of drug resistance. METHODS: (1) HCE1/MCS was obtained using liquid overlay and rotating technique. (2) Four groups were established (MG132 group, cisplatin group, MG132+cisplatin group, the control group). Cell viability were measured by trypan blue exclusion assay. Cell cycle and apoptosis were detected by flow cytometry. (3) The expression of nuclear factor (NF) kappaB of both HCE1 monolayer cells (HCE1/MC) and HCE1/MCS was detected by western blot, and the expression of B cell lymphoma/leukemia-2 (bcl-2) was detected by immunohistochemistry. RESULTS: (1) HCE1/MCS was established successfully. (2) Cell inhibited rate of HCE1/MC and HCE1/MCS was: in MG132 group, (11.67+/-2.34)% vs (10.78+/-1.17)% (P>0.05); in MG132+cisplatin group, (92.67+/-2.52)% vs (91.33+/-2.18)% (P>0.05); in cisplatin group, (45.01+/-7.44)% vs (9.45+/-5.98)% (P<0.05). (3) The rate of apoptosis of HCE1/MC and HCE1/MCS were: in MG132 group, 8.14% and 5.97%; in MG132+cisplatin group, 99.01% and 95.22%; in cisplatin group, 33.61% and 0.88%. (4) The expression level of NF-kappaB and the high expression rate of bcl-2 were: in HCE1/MCS of control group, 0.67 and 60%; in HCE1/MCS of cisplatin group, 0.85 and 83%; in HCE1/MCS of MG132 group, 0.39 and 20%; in HCE1/MCS of MG132+cisplatin group, 0.47 and 33%. CONCLUSIONS: (1) HCE1/MCS present natural resistance to cisplatin and may become a good model for the study of cervical cancer drug resistance in vitro. (2) MG132 could induce the inhibition and apoptosis of HCE1/MCS cells and partially reverse the natural resistance of HCE1/MCS to cisplatin, of which partially reverse the natural resistance may be in relation to the down-regulation of NF-kappaB and bcl-2 expression.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Leupeptinas/farmacologia , Esferoides Celulares/patologia , Neoplasias do Colo do Útero/patologia , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Leupeptinas/administração & dosagem , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Esferoides Celulares/metabolismo , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/metabolismoRESUMO
OBJECTIVE: To investigate whether there are some differences in the accuracy of Acrysof Toric intraocular lens (IOL) implantation and the ability to correct astigmatism between 2 types of clear corneal incisions used in phacoemulsification: the on-axis (i.e on the steeper corneal meridian) and the temporal clear corneal incision (OCCI and TCCI, respectively). METHODS: In this prospective study, thirty-nine eyes with cataract and mild to moderate corneal astigmatism (1.00 - 2.26 diopters on corneal curvature) were recruited and divided into OCCI group (20 eyes) and TCCI group (19 eyes) respectively. All of these patients underwent phacoemulsification and an Acrysof Toric IOL implantation (single surgeon, 3.2 mm incision). Main outcome measurements included uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), corneal curvature, surgically induced astigmatism (SIA), deviation of lens axis (LAD), index of corrected astigmatism (CAI) and accuracy of astigmatism correction (ACA) at 3 months postoperatively. RESULTS: At 3 months postoperatively, simple algebraic difference showed a mean increase in the astigmatism magnitude of (0.28 + or - 0.27) D in the TCCI group and a mean reduction in the astigmatism magnitude of (0.31 + or - 0.26) D in the OCCI group (t = 5.756, F = 0.000). The average LAD was 0 degrees + or - 0 degrees in the OCCI group and 2.22 degrees + or - 2.99 degrees in the TCCI group(t = 3.860, P = 0.000). The average CAI were 1.04 + or - 0.27 and 0.59 + or - 0.44 respectively (t = 3.187, P = 0.004). The ACA were 0.838 and 0.484 respectively (Z = 1.970, P = 0.049). CONCLUSIONS: Compared with the TCCI, the OCCI could correct some corneal astigmatism and reduce IAD induced by the SIA shift. As a result, the OCCI could improve the accuracy of Acrysof Toric lens implantation and the ability to correct astigmatism.
Assuntos
Catarata/terapia , Implante de Lente Intraocular/métodos , Facoemulsificação/métodos , Idoso , Astigmatismo/cirurgia , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. MATERIALS AND METHODS: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. RESULTS: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. CONCLUSION: RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.
Assuntos
Biomarcadores Tumorais/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met/genética , Receptores Proteína Tirosina Quinases/genética , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Programmed death ligand 1 (PD-L1) immunotherapy remains poorly efficacious in colorectal cancer (CRC). The recepteur d'origine nantais (RON) receptor tyrosine kinase plays an important role in regulating tumor immunity. AIM: To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC. METHODS: Gene expression data from the Gene Expression Omnibus database (GEO; n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM; n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot. RESULTS: In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121 (32%), 43 (11%), 91 (24%), and 51 (13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment (P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells. CONCLUSION: RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.