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Visual anomaly detection is an essential component in modern industrial manufacturing. Existing studies using notions of pairwise similarity distance between a test feature and nominal features have achieved great breakthroughs. However, the absolute similarity distance lacks certain generalizations, making it challenging to extend the comparison beyond the available samples. This limitation could potentially hamper anomaly detection performance in scenarios with limited samples. This article presents a novel sparse feature representation anomaly detection (SFRAD) framework, which formulates the anomaly detection as a sparse feature representation problem; and notably proposes an anomaly score by orthogonal matching pursuit (ASOMP) as a novel detection metric. Specifically, SFRAD calculates the Gaussian kernel distance between the test feature and its sparse representation in the nominal feature space for anomaly detection. Here, the orthogonal matching pursuit (OMP) algorithm is adopted to achieve the sparse feature representation. Moreover, to construct a low-redundancy memory bank storing the basis features for sparse representation, a novel basis feature sampling (BFS) algorithm is proposed by considering both the maximum coverage and the optimum feature representation simultaneously. As a result, SFRAD incorporates both the advantages of absolute similarity and linear representation; and this enhances the generalization in low-shot scenarios. Extensive experiments on the MVTec anomaly detection (MVTec AD), Kolektor surface-defect dataset (KolektorSDD), Kolektor surface-defect dataset 2 (KolektorSDD2), MVTec logical constraints anomaly detection (MVTec LOCO AD), Visual anomaly (VISA), Modified national institute of standards and technology (MNIST), and CIFAR-10 datasets demonstrate that our proposed SFRAD outperforms the previous methods and achieves state-of-the-art unsupervised anomaly detection performance. Notably, significantly improved outcomes and results have also been achieved on low-shot anomaly detection. Code is available at https://github.com/fanghuisky/SFRAD.
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Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.
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Herbivoria , Transcriptoma , Animales , Bovinos/genética , Femenino , Conejos/genética , Bases de Datos Genéticas , Ciervos/genética , Equidae/genética , Cabras/genética , Caballos/genética , Ovinos/genéticaRESUMEN
Major depressive disorder (MDD) involves systemic changes in peripheral blood and gut microbiota, but the current understanding is incomplete. Herein, we conducted a multi-omics analysis of fecal and blood samples obtained from an observational cohort including MDD patients (n = 99) and healthy control (HC, n = 50). 16S rRNA sequencing of gut microbiota showed structural alterations in MDD, as characterized by increased Enterococcus. Metagenomics sequencing of gut microbiota showed substantial functional alterations including upregulation in the superpathway of the glyoxylate cycle and fatty acid degradation and downregulation in various metabolic pathways in MDD. Plasma metabolomics revealed decreased amino acids and bile acids, together with increased sphingolipids and cholesterol esters in MDD. Notably, metabolites involved in arginine and proline metabolism were decreased while sphingolipid metabolic pathway were increased. Mass cytometry analysis of blood immune cell subtypes showed rises in proinflammatory immune subsets and declines in anti-inflammatory immune subsets in MDD. Furthermore, our findings revealed disease severity-related factors of MDD. Interestingly, we classified MDD into two immune subtypes that were highly correlated with disease relapse. Moreover, we established discriminative signatures that differentiate MDD from HC. These findings contribute to a comprehensive understanding of the MDD pathogenesis and provide valuable resources for the discovery of biomarkers.
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Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Humanos , Disbiosis/complicaciones , Multiómica , ARN Ribosómico 16SRESUMEN
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) was associated with potentially life-threatening complications. Among patients supported by extracorporeal membrane oxygenation (ECMO), those who underwent HSCT had a worse prognosis than those who did not. Advances in HSCT and critical care management have improved the prognosis of ECMO-supported HSCT patients. CASE: The patient in the remission stage of lymphoma after 22 months of allogeneic hematopoietic stem cell transplantation, suffered from ARDS, severe neutropenia, thrombocytopenia, and long-term COVID-19. We evaluated the benefits and risks of ECMO for the patient, including the possibility of being free from ECMO, the status of malignancy, the interval from HSCT to ARDS, the function of the graft, the amount of organ failure, and the comorbidities. ECMO was ultimately used to save his life. CONCLUSIONS: We did not advocate for the general use of ECMO in HSCT patients and we believed that highly selected patients, with well-controlled tumors, few comorbidities, and fewer risk factors for death, tended to benefit from ECMO with well ICU management.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Neutropenia , Síndrome de Dificultad Respiratoria , Trombocitopenia , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , COVID-19/terapia , COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Trombocitopenia/terapia , Trombocitopenia/complicaciones , Neutropenia/complicaciones , Neutropenia/terapia , Neoplasias/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Major depressive disorder (MDD) is a major international public health issue; thus, investigating its underlying mechanisms and identifying suitable biomarkers to enable its early detection are imperative. Using data-independent acquisition-mass spectrometry-based proteomics, the plasma of 44 patients with MDD and 25 healthy controls was studied to detect differentially expressed proteins. Bioinformatics analyses, such as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, Protein-Protein Interaction network, and weighted gene co-expression network analysis were employed. Moreover, an ensemble learning technique was used to build a prediction model. A panel of two biomarkers, L-selectin and an isoform of the Ras oncogene family was identified. With an area under the receiver operating characteristic curve of 0.925 and 0.901 for the training and test sets, respectively, the panel was able to distinguish MDD from the controls. Our investigation revealed numerous potential biomarkers and a diagnostic panel based on several algorithms, which may contribute to the future development of a plasma-based diagnostic approach and better understanding of the molecular mechanisms of MDD.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Proteómica , Biomarcadores , Algoritmos , Aprendizaje AutomáticoRESUMEN
ABSTRACT: Introduction: Septic patients with atrial fibrillation (AF) are common in the intensive care unit accompanied by high mortality. The early prediction of prognosis of these patients is critical for clinical intervention. This study aimed to develop a model by using machine learning (ML) algorithms to predict the risk of 28-day mortality in septic patients with AF. Methods: In this retrospective cohort study, we extracted septic patients with AF from the Medical Information Mart for Intensive Care III (MIMIC-III) and IV database. Afterward, only MIMIC-IV cohort was randomly divided into training or internal validation set. External validation set was mainly extracted from MIMIC-III database. Propensity score matching was used to reduce the imbalance between the external validation and internal validation data sets. The predictive factors for 28-day mortality were determined by using multivariate logistic regression. Then, we constructed models by using ML algorithms. Multiple metrics were used for evaluation of performance of the models, including the area under the receiver operating characteristic curve, sensitivity, specificity, recall, and accuracy. Results: A total of 5,317 septic patients with AF were enrolled, with 3,845 in the training set, 960 in the internal testing set, and 512 in the external testing set, respectively. Then, we established four prediction models by using ML algorithms. AdaBoost showed moderate performance and had a higher accuracy than the other three models. Compared with other severity scores, the AdaBoost obtained more net benefit. Conclusion: We established the first ML model for predicting the 28-day mortality of septic patients with AF. Compared with conventional scoring systems, the AdaBoost model performed moderately. The model established will have the potential to improve the level of clinical practice.
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Fibrilación Atrial , Sepsis , Humanos , Estudios Retrospectivos , Algoritmos , Unidades de Cuidados Intensivos , Aprendizaje AutomáticoRESUMEN
Angiotensin II (Ang II) is a kind of bioactive peptide, which can contribute to cardiac hypertrophy. MicroRNAs (miRNAs) play critical role in various heart diseases. The cardioprotective effect of miR-423-5p inhibition has been confirmed by previous studies. But its role in cardiac hypertrophy induced by Ang II is unknown. This study focused on the potential of miR-423-5p in cardiomyocyte hypertrophy under the treatment of Ang II. Our results revealed that miR-423-5p expression was upregulated in Ang II-treated human cardiomyocytes (HCMs). Importantly, miR-423-5p knockdown suppressed Ang II-induced cardiomyocyte hypertrophy and oxidative stress in HCMs. Bioinformatics analysis and luciferase reporter assay confirmed that the suppressor of Ty 6 homolog (SUPT6H) was a target gene of miR-423-5p. Interestingly, SUPT6H knockdown aggravated cardiomyocyte hypertrophy and oxidative stress in Ang II-stimulated HCMs, which were then reversed by silenced miR-423-5p. In conclusion, miR-423-5p knockdown exerts its protective effects on Ang II-induced cardiomyocyte hypertrophy in HCMs via modulating SUPT6H expression.
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MicroARNs , Miocitos Cardíacos , Humanos , Miocitos Cardíacos/metabolismo , Angiotensina II/farmacología , Angiotensina II/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: The role of transvaginal sonography (TVS) in screening endometrial cancer and hyperplasia is significant in postmenopausal women. The objective of this study is to determine the endometrium thickness (ET) cut-off to distinguish premalignancy and malignancy in asymptomatic postmenopausal women. METHODS: We retrospectively evaluated data of 968 eligible patients among 2537 asymptomatic postmenopausal women with ET ≥ 5 mm examined by TVS who were subjected to hysteroscopy and endometrial biopsy between January 1, 2017, and June 30, 2020 in an urban tertiary specialized hospital in China. The patients were divided into two groups according to the pathology outcomes: benign, and atypical hyperplasia (AH) and endometrial carcinoma (EC). The risk factors and the optimal cut-off of ET for detecting AH and EC were determined by logistic regression analysis and receiver operating characteristic curve. RESULTS: 2537 patients were offered hysteroscopy during a 42-month period. Finally, 968 patients were included for further analysis. Of these, 8 (0.8%) women were diagnosed with EC and 5 (0.5%) women with AH. The mean ET of AH and EC group was substantially higher than that in benign group (10.4 mm vs. 7.7 mm, P < 0.05). ET was significantly correlated with AH and EC shown by logistic regression analysis with an odds ratio (OR) of 1.252 (95% confidence interval [CI] 1.107-1.416, P < 0.001). The optimal cut-off value for AH and EC was found to be 8 mm with the maximum AUC of 0.715 (95% CI 0.686-0.743, P < 0.001), with a sensitivity of 0.846, a specificity of 0.609, positive likelihood ratio (LR+) of 2.164 and negative likelihood ratio (LR-) of 0.253. CONCLUSION: An ET cut-off of ≥ 8 mm shows a reasonable performance to detect AH and EC in asymptomatic postmenopausal women, thereby avoiding more invasive endometrial biopsy.
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Neoplasias Endometriales , Lesiones Precancerosas , Humanos , Femenino , Embarazo , Masculino , Hiperplasia/complicaciones , Hiperplasia/patología , Estudios Retrospectivos , Posmenopausia , Ultrasonografía/efectos adversos , Neoplasias Endometriales/diagnóstico por imagen , Histeroscopía/efectos adversos , Endometrio/diagnóstico por imagen , Endometrio/patología , Hemorragia Uterina/etiologíaRESUMEN
INTRODUCTION: Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes. METHODS AND ANALYSIS: iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants' responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04518592.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Estudios Prospectivos , China , Biomarcadores , Inhibidores Selectivos de la Recaptación de SerotoninaRESUMEN
Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What's more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults.
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AMP Cíclico , Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculosis Ganglionar , Aciltransferasas/genética , Adenosina Monofosfato , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Animales , Antígenos Bacterianos , Vacuna BCG , AMP Cíclico/química , Citocinas/metabolismo , Fosfatos de Dinucleósidos , Ratones , Ratones Endogámicos C57BL , Vacunas SintéticasRESUMEN
The increasing demand for higher-quality medical care has resulted in the obsolescence of traditional biomaterials. Medical care is currently transitioning from an era depending on single-functional biomaterials to one that is supported by multifunctional and stable biomaterials. Herein, long-lasting multifunctional poly(ether sulfone) thin films (MPFs) containing heparin-mimic groups and a quaternary ammonium compound (QAC) were prepared via semi-interpenetrating polymer network (SIPN) strategy. The MPFs, with rough surface and inner finger-like macrovoid, had better hydrophilicity and anti-protein fouling ability, as revealed by scanning electron microscopy (SEM), atomic force microscope (AFM) and water contact angle (WCA) and protein adsorption tests. The results of platelet adhesion and activation, and clotting time confirmed that the hemocompatibility of the MPFs was significantly improved. From cell culture and germ-culture test, it was noted that the overall trend of human umbilical vein endothelial cell (HUVEC) proliferation was enhanced by a combination of heparin-mimic groups and QAC, whereas the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was significantly prohibited. In addition, the MPFs were capable of modulating the expression level of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-ß1) in fibroblast, which was beneficial to controlling the formation of hypertrophic scar. In summary, the MPFs had potential to be used in the field of wound management and the study might help guide the design of surface structure of wound dressing.
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Escherichia coli , Staphylococcus aureus , Vendajes , Materiales Biocompatibles/química , Éter , Heparina/farmacología , Humanos , SulfonasRESUMEN
ANO1, a calcium-activated chloride channel (CACC), is also known as transmembrane protein 16A (TMEM16A). It plays a vital role in the occurrence, development, metastasis, proliferation, and apoptosis of various malignant tumors. This article reviews the mechanism of ANO1 involved in the replication, proliferation, invasion and apoptosis of various malignant tumors. Various molecules and Stimuli control the expression of ANO1, and the regulatory mechanism of ANO1 is different in tumor cells. To explore the mechanism of ANO1 overexpression and activation of tumor cells by studying the different effects of ANO1. Current studies have shown that ANO1 expression is controlled by 11q13 gene amplification and may also exert cell-specific effects through its interconnected protein network, phosphorylation of different kinases, and signaling pathways. At the same time, ANO1 also resists tumor apoptosis and promotes tumor immune escape. ANO1 can be used as a promising biomarker for detecting certain malignant tumors. Further studies on the channels and the mechanism of protein activity of ANO1 are needed. Finally, the latest inhibitors of ANO1 are summarized, which provides the research direction for the tumor-promoting mechanism of ANO1.
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Transition metal ion-activated sulfite autoxidation processes for the production of sulfate radicals (SO4Ë-) have been widely investigated to achieve efficient abatement of recalcitrant organic pollutants. However, these homogeneous processes suffered from narrow effective pH range and metal release, thus restricting their practical application. In order to address this problem, we report a simple and efficient approach to iohexol abatement by a combined Cu2S and sulfite process (simplified as Cu2S/sulfite process) based on the superior activation performance of copper and the excellent electron donating capacity of the low-valent sulfur species. Compared with typical copper oxides, Cu2S can significantly accelerate the sulfite autoxidation to generate radicals, leading to 100% iohexol abatement in the Cu2S/sulfite process. The influence of solution pH and dissolved oxygen on iohexol abatement is also investigated. Qualitative and quantitative analysis of reactive radicals is performed by electron paramagnetic resonance (EPR) and radical quenching experiments. Generation of SO4Ë- from sulfite activation with Cu2S mainly contributes to the iohexol abatement. X-ray photoelectron spectroscopy (XPS) suggests that copper is the main activation site and the reductive sulfur species can achieve the continuous regeneration of copper. Application potential of the Cu2S/sulfite process is also assessed. This study provides a new method for the treatment of water and wastewater containing organic micropollutants.
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Maize is an important cereal crop but is sensitive to heat stress, which significantly restricts its grain yield. To explore the molecular mechanism of maize heat tolerance, a heat-tolerant hybrid ZD309 and its parental lines (H39_1 and M189) were subjected to heat stress, followed by transcriptomic and metabolomic analyses. After six-day-heat treatment, the growth of ZD309 and its parental lines were suppressed, showing dwarf stature and rolled leaf compared with the control plants. ZD309 exhibited vigorous growth; however, M189 displayed superior heat tolerance. By transcriptomic and metabolomic analysis, hundreds to thousands of differentially expressed genes (DEGs) and metabolites (DEMs) were identified. Notably, the female parent H39 shares more DEGs and DEMs with the hybrid ZD309, indicating more genetic gain derived from the female instead of the male. A total of 299 heat shock genes detected among three genotypes were greatly aggregated in sugar transmembrane transporter activity, plasma membrane, photosynthesis, protein processing in the endoplasmic reticulum, cysteine, and methionine metabolism. A total of 150 heat-responsive metabolites detected among three genotypes were highly accumulated, including jasmonic acid, amino acids, sugar, flavonoids, coumarin, and organic acids. Integrating transcriptomic and metabolomic assays revealed that plant hormone signal transduction, cysteine, and methionine metabolism, and α-linolenic acid metabolism play crucial roles in heat tolerance in maize. Our research will be facilitated to identify essential heat tolerance genes in maize, thereby contributing to breeding heat resistance maize varieties.
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Pevonedistat is a neddylation inhibitor that blocks proteasomal degradation of cullin-RING ligase (CRL) proteins involved in the degradation of short-lived regulatory proteins, including those involved with cell-cycle regulation. We determined the sensitivity and mechanism of action of pevonedistat cytotoxicity in neuroblastoma. Pevonedistat cytotoxicity was assessed using cell viability assays and apoptosis. We examined mechanisms of action using flow cytometry, bromodeoxyuridine (BrDU) and immunoblots. Orthotopic mouse xenografts of human neuroblastoma were generated to assess in vivo anti-tumor activity. Neuroblastoma cell lines were very sensitive to pevonedistat (IC50 136-400 nM). The mechanism of pevonedistat cytotoxicity depended on p53 status. Neuroblastoma cells with mutant (p53MUT) or reduced levels of wild-type p53 (p53si-p53) underwent G2-M cell-cycle arrest with rereplication, whereas p53 wild-type (p53WT) cell lines underwent G0-G1 cell-cycle arrest and apoptosis. In orthotopic neuroblastoma models, pevonedistat decreased tumor weight independent of p53 status. Control mice had an average tumor weight of 1.6 mg + 0.8 mg versus 0.5 mg + 0.4 mg (p < 0.05) in mice treated with pevonedistat. The mechanism of action of pevonedistat in neuroblastoma cell lines in vitro appears p53 dependent. However, in vivo studies using mouse neuroblastoma orthotopic models showed a significant decrease in tumor weight following pevonedistat treatment independent of the p53 status. Novel chemotherapy agents, such as the NEDD8-activating enzyme (NAE) inhibitor pevonedistat, deserve further study in the treatment of neuroblastoma.
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Antineoplásicos/uso terapéutico , Ciclopentanos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Pirimidinas/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ciclopentanos/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Ratones , Proteína NEDD8/antagonistas & inhibidores , Proteína NEDD8/metabolismo , Pirimidinas/farmacología , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
In the present study, a model of glioma stem cells (GSCs) was established and combined with molecular targeting drugs in order to observe its inhibitory effect on the proliferation and biological characteristics of GSCs, with the aim of providing a potential target for the treatment of glioma. On the basis of a relatively classical induction strategy with neuron induction medium, a large number of GSC-like cells in good condition and globular growth were amplified in vitro, which had the potential to differentiate into neurons, oligodendrocytes and astrocytes/glioma cells. It was observed that the interference with dynamin-related protein 1 expression using Mdivi-1, a mitochondrial mitotic inhibitor, at the optimal concentration, decreased the expression level of stem cell-associated genes, inhibited proliferation and promoted apoptosis in GSCs. The present study provided an experimental basis for a novel strategy of cancer treatment with tumor stem cells as the target.
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No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The present study investigated the potential of a combined medium composed of conditioned medium and eight small molecular compounds in reprogramming human foreskin fibroblasts (HFFs) into neurons. HFFs were cultured from foreskin and then induced by small molecules to generate neurons. The results demonstrated that the conditioned medium containing forskolin, RepSox, SP600125, CHIR99021, Go6983, Y27632, IXS9 and IBET151 effectively induced human fibroblasts to change into neurons in vitro. Following a 30day induction, the cells exhibited neuronal properties as determined by morphological and phenotypical alterations. The induced cells exhibited expression of neuronal markers, including class III ßtubulin, microtubuleassociated protein 2, vesicular glutamate transporter 1 and γaminobutyric acid, accompanied by increased expression of neuronal transcription factors, including neuronal differentiation 1 and achaetescute family bHLH transcription factor 1, and decreased expression levels of fibroblastspecific genes. Furthermore, these cells also exhibited electrophysiological properties of neurons. Notably, the course of cell morphological alterations demonstrated the differentiation of fibroblasts into neurons. The present study provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons.
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Diferenciación Celular/efectos de los fármacos , Técnicas de Reprogramación Celular/métodos , Reprogramación Celular/fisiología , Amidas/química , Antracenos/química , Diferenciación Celular/fisiología , Células Cultivadas , Colforsina/química , Medios de Cultivo Condicionados/farmacología , Fibroblastos/metabolismo , Prepucio/citología , Humanos , Indoles/química , Masculino , Maleimidas/química , Proteínas del Tejido Nervioso/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo , Pirazoles/química , Piridinas/química , Pirimidinas/química , Factores de Transcripción/genéticaRESUMEN
A geometric error determines the quality and function of a product to a certain extent. Cylindricity error is an important indicator of the geometric error of form parts. In recent years, with the development of geometric product verification and specification (GPS), the specification of the cylindricity error and high-precision detection have become the focus in the field of industrial metrology. In this paper, by analyzing the existing cylindricity evaluation strategy, a new method for cylindricity error evaluation based on increment-simplex algorithm is proposed. The purpose is to improve the efficiency of cylindricity error analysis on the basis of ensuring the accuracy requirements. First, according to the GPS specification, the characteristics and applications of the circular section method, the helicoid line method, the generatrix line method, and the bird-cage method for the extraction operation are analyzed. And for the fitting operation, the mathematical models of the cylindricity fitting for the least squares cylinder, minimum circumscribed cylinder, maximum inscribed cylinder, and minimum zone cylinder in cartesian and cylindrical coordinate systems are constructed. Second, a new method of cylindricity error optimization evaluation based on the incremental optimization method is proposed. A theoretical analysis of the new method is made with the circular section method as an example, and the specific steps of cylindricity error analysis based on the circular section method of the new method are given. Finally, experiments and analysis are carried out, and the accuracies and evaluation efficiencies of the cylindricity error of the different cylindricity measurement and evaluation strategies are compared and analyzed. The results and operating efficiency of the increment-simplex algorithm and the traditional algorithms are compared, and the effectiveness and feasibility of the new method are proved.