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BACKGROUND: Non-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS. METHODS: This is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People's Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS. RESULTS: We had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45-12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55-16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727-0.896; p < 0.001). CONCLUSION: Our results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.
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Accidente Cerebrovascular Embólico , Embolia , Hipertensión , Embolia Intracraneal , Placa Aterosclerótica , Accidente Cerebrovascular , Estudios Transversales , Humanos , Hipertensión/complicaciones , Embolia Intracraneal/complicaciones , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/epidemiología , Placa Amiloide , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiologíaRESUMEN
PURPOSE: Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. METHODS: The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. RESULTS: The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p < 0.05). YKL-40 levels were significantly different between chronic obstructive pulmonary disease (COPD) and asthma, and also between asthma-COPD overlap syndrome (ACO) and asthma (p < 0.05). CONCLUSION: YKL-40 may act as a potential serological marker for the diagnosis of asthma, assessment of severity, indicator of the disease state, and differential diagnosis of COPD, ACO, and asthma.
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Asma , Proteína 1 Similar a Quitinasa-3/sangre , Enfermedad Pulmonar Obstructiva Crónica , Biomarcadores , Diagnóstico Diferencial , HumanosRESUMEN
BACKGROUND: Few studies have investigated the influence of white matter lesions (WMLs) on the prognosis of acute cardioembolic stroke (CES). We aimed to explore the role of WMLs in predicting 3-month prognosis of CES without reperfusion therapy. METHODS: A number of 251 acute CES patients without reperfusion therapy at a single center were retrospectively recruited. The severity of WMLs was evaluated by Fazekas scale and patients were divided into mild WMLs group (188 cases, Fazekas ≤ 2 points) and moderate to severe WMLs group (63 cases, Fazekas ≥ 3 points) accordingly. General data and clinical features of the two groups were compared. Functional outcomes of patients were followed up for 3 months using the modified Rankin scale (mRS) and patients were divided into poor outcome group (mRS ≥ 3) and favorable outcome group (mRS ≤ 2). The effect of WMLs on the prognosis was identified by binary logistic regression. RESULTS: Patients in moderate to severe WMLs group were older (P < 0.001). Also, they had higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) and elevated incidence of asymptomatic cerebral hemorrhage (P = 0.040) and stroke associated pneumonia (P = 0.001) than those in mild WMLs group. At 3 months, there were 100 cases in the poor outcome group. Patients in poor outcome group had higher baseline NIHSS score, increased proportion of moderate to severe WMLs, and elevated incidence of stroke associated pneumonia than those in favorable outcome group (P < 0.001). Binary logistic regression analysis showed that moderate to severe WMLs (odds ratio [OR] = 4.105, 95 % confidence interval [CI] = 1.447-11.646), baseline NIHSS score (OR = 1.368, 95 % CI = 1.240-1.511), and stroke-associated pneumonia (OR = 4.840, 95 %CI = 1.889-12.400) were independent risk factors for poor outcome. CONCLUSIONS: Moderate to severe WMLs is an independent risk factor for prognosis of CES patients without reperfusion therapy.
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Accidente Cerebrovascular Embólico , Accidente Cerebrovascular , Sustancia Blanca , Humanos , Pronóstico , Reperfusión , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Resultado del Tratamiento , Sustancia Blanca/diagnóstico por imagenRESUMEN
Attaining control on charge injection properties is significant for meaningful applications of organic field-effect transistors (OFETs). Here, molecular electron-doping is applied with an air-stable dimer dopant for n-type OFETs based on (naphthalene diimide-diketopyrrolopyrrole) polymer hosts. Through investigating the doping effect on contact and transport properties, it is found that the electron transport increases in n-doped OFETs at low doping regime with remaining large on/off ratios. These favorable meliorations are reconciled by the mitigated impacts of contact resistance and interfacial traps, as well as the surface morphology exhibiting features of increased ordering. The occurrence of doping in the presence of dimer dopants is evidenced by the observed shift of Fermi level toward vacuum level coupled with compositional analysis. Without applying vacuum-deposition-based contact doping, charge injection efficiencies are gained without losing OFET characteristics using the solution-based methodology.
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Transporte de Electrón , Compuestos Orgánicos/química , Polímeros/química , Imidas/química , Cetonas/química , Naftalenos/química , Pirroles/química , Semiconductores , Transistores ElectrónicosRESUMEN
OBJECTIVE: The relationship between tobacco smoke exposure (TSE) and depression is controversial. This study combined observational research and Mendelian randomization (MR) to explore the relationship of depression with both smoking status and cotinine levels. METHOD: We collected relevant data from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018, and used weighted multifactorial logistic regression modelling to assess the correlation between TSE and depression, and assessed the causal relationship of depression with both smoking status and cotinine levels by MR. RESULT: Current smokers had the highest risk of depression (OR 1.94; P < 0.01); there was a positive trend for correlation between daily smoking and depression (OR 1.66; P for trend < 0.01). Serum ketamine levels above 3.00 ng/ml had a higher risk of depression (OR 2.13; P < 0.001). MR results showed that current smoking (OR = 4.66; P < 0.001) and previous smoking (OR 2.09; P < 0.01) were risk factors for the onset of depression, and that there was no causal association between cotinine levels and depression. CONCLUSION: Smoking is significantly associated with depression and plays a potential causal role in the development of depression. Cotinine was significantly associated with depression, however MR results showed no causal relationship between cotinine and depression.
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Purpose: This study was to explore the role of pre-existing small vessel disease (SVD) on the 3-month outcomes of acute cardioembolic stroke (CES) patients. Patients and Methods: Data of 189 consecutive acute CES patients at a single center were retrospectively enrolled. SVD imaging markers of lacunes, white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) were evaluated and their total burden score (0-3 points) was calculated. Patients were divided into the good functional outcome group (modified Rankin scale, mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3) at 3 months after stroke onset. The effect of each single SVD marker and its total burden score on the outcome was identified using binary logistic regression. Results: Overall, 100 (52.9%), 52 (27.1%), 28 (14.8%) and 9 (4.8%) patients had 0, 1, 2 and 3 SVD imaging markers. Patients with a total SVD burden score of 2 and 3 were significantly older and had higher baseline National Institutes of Health Stroke Scale (NIHSS) score than those with a score of 0 and 1 (P<0.01). Forty-seven (24.9%) patients had a poor outcome. Patients in the poor outcome group had significantly higher baseline NIHSS score, increased incidence of stroke associated pneumonia, and heavier burden of lacunes, WMH and EPVS, and thus had elevated total SVD burden score than those in good outcome group (P<0.05). After adjusting for potential confounders, the WMH (odds ratio [OR] = 2.6777, 95% confidence interval [CI] = 1.052-6.812, P = 0.039) and the total SVD burden score (OR = 1.717, 95% CI = 1.072-2.749, P = 0.024) were, respectively, independent risk factors for a poor outcome. Conclusion: The pre-existing SVD may be associated with the 3-month prognosis of CES.
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NEKs are proteins that are involved in various cell processes and play important roles in the formation and development of cancer. However, few studies have examined the role of NEKs in the development of non-small-cell lung carcinoma (NSCLC). To address this problem, the Oncomine, UALCAN, and the Human Protein Atlas databases were used to analyze differential NEK expression and its clinicopathological parameters, while the Kaplan-Meier, cBioPortal, GEPIA, and DAVID databases were used to analyze survival, gene mutations, similar genes, and biological enrichments. The rate of NEK family gene mutation was high (> 50%) in patients with NSCLC, in which NEK2/4/6/8/ was overexpressed and significantly correlated with tumor stage and nodal metastasis status. In addition, the high expression of NEK2/3mRNA was significantly associated with poor prognosis in patients with NSCLC, while high expression of NEK1/4/6/7/8/9/10/11mRNA was associated with good prognosis. In summary, these results suggest that NEK2/4/6/8 may be a potential prognostic biomarker for the survival of patients with NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Quinasas Relacionadas con NIMA/genética , Proteómica/métodos , Transcriptoma/genética , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Bases de Datos de Proteínas , Humanos , Estimación de Kaplan-Meier , Mutación , Pronóstico , ARN Mensajero/genética , Tasa de SupervivenciaRESUMEN
PURPOSE: Few clinical indicators of a poor outcome have been defined in acute cardioembolic stroke (CES) patients. We would like to explore practical clinical factors that can predict poor outcomes of CES in the early stage. PATIENTS AND METHODS: In this single-center, retrospective, observational study, 251 consecutive patients with acute CES who did not undergo reperfusion therapy were evaluated. On the basis of the modified Rankin Scale (mRS) score at 3 months, patients were divided into the good functional outcome group (mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3). Risk factors were analyzed and the independent indicators for a poor outcome were identified using a binary logistic regression model. RESULTS: One hundred (39.8%) patients had a poor outcome. Patients in the poor outcome group were significantly older (P = 0.002) and had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) score compared with those with a good outcome (P < 0.001). After adjusting for potential confounders, the baseline NIHSS score (P < 0.001), moderate to severe leukoaraiosis (P = 0.011), non-symptomatic intracranial hemorrhage (P = 0.019), stroke-associated pneumonia (P = 0.001), and fasting glucose (P = 0.040) were independent risk factors for a poor outcome. CONCLUSION: The short-term outcome in acute CES patients without reperfusion therapy can be predicted by using five practical clinical factors. These indicators should attract more attention.
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Word Sense Disambiguation (WSD), the automatic identification of the meanings of ambiguous terms in a document, is an important stage in text processing. We describe a WSD system that has been developed specifically for the types of ambiguities found in biomedical documents. This system uses a range of knowledge sources. It employs both linguistic features, such as local collocations, and features derived from domain-specific knowledge sources, the Unified Medical Language System (UMLS) and Medical Subject Headings (MeSH). This system is applied to three types of ambiguities found in Medline abstracts: ambiguous terms, abbreviations with multiple expansions and names that are ambiguous between genes. The WSD system is applied to the standard NLM-WSD data set, which consists of ambiguous terms from Medline abstracts, and was found to perform well in comparison with previously reported results. The system's performance and the contribution of each knowledge source depends upon the type of lexical ambiguity. 87.9% of the ambiguous terms are correctly disambiguated using a combination of linguistic features and MeSH terms, 99% of abbreviations are disambiguated by combining all knowledge sources, while 97.2% of ambiguous gene names are disambiguated using the MeSH terms alone. Analysis reveals that these differences are caused by the nature of each ambiguity type. These results should be taken into account when deciding which information to use for WSD and the level of performance that can be expected.
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Biología Computacional/métodos , Procesamiento de Lenguaje Natural , MEDLINE , Medical Subject Headings , Unified Medical Language System , Estados Unidos , Vocabulario ControladoRESUMEN
Researchers have access to a vast amount of information stored in textual documents and there is a pressing need for the development of automated methods to enable and improve access to this resource. Lexical ambiguity, the phenomena in which a word or phrase has more than one possible meaning, presents a significant obstacle to automated text processing. Word Sense Disambiguation (WSD) is a technology that resolves these ambiguities automatically and is an important stage in text understanding. The most accurate approaches to WSD rely on manually labeled examples but this is usually not available and is prohibitively expensive to create. This paper offers a solution to that problem by using information in the UMLS Metathesaurus to automatically generate labeled examples. Two approaches are presented. The first is an extension of existing work (Liu et al., 2002 [1]) and the second a novel approach that exploits information in the UMLS that has not been used for this purpose. The automatically generated examples are evaluated by comparing them against the manually labeled ones in the NLM-WSD data set and are found to outperform the baseline. The examples generated using the novel approach produce an improvement in WSD performance when combined with manually labeled examples.
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Bases de Datos Factuales , Informática Médica/métodos , Procesamiento de Lenguaje Natural , Terminología como Asunto , Unified Medical Language System , Medical Subject Headings , Reproducibilidad de los ResultadosRESUMEN
GH secretagogue receptor (ghrelin receptor, GHSR) is known to be involved in the control of GH release by mediating the strong stimulatory effect of the endogenous ligand, ghrelin, on GH secretion. Associations between the GHSR gene polymorphism and the growth traits were revealed in Nanyang cattle. The mutations at nt456(G > A) and nt667(C > T) were complete linkage and located in exon 1 of the coding region of the GHSR gene. Least squares analysis revealed a significant statistical effect (P < 0.05) of the GHSR gene different genotypes on body weight and average daily gain at 6 months of age in Nanyang cattle. Individuals with GHSR-MM genotype showed higher body weight and average daily gain than individuals with GHSR-MN genotype.
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Bovinos/genética , Receptores de Ghrelina/genética , Animales , Peso Corporal , Cruzamiento , Bovinos/crecimiento & desarrollo , China , Estudios de Asociación Genética/métodos , Análisis de los Mínimos Cuadrados , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
In this paper, we describe the construction of a semantically annotated corpus of clinical texts for use in the development and evaluation of systems for automatically extracting clinically significant information from the textual component of patient records. The paper details the sampling of textual material from a collection of 20,000 cancer patient records, the development of a semantic annotation scheme, the annotation methodology, the distribution of annotations in the final corpus, and the use of the corpus for development of an adaptive information extraction system. The resulting corpus is the most richly semantically annotated resource for clinical text processing built to date, whose value has been demonstrated through its use in developing an effective information extraction system. The detailed presentation of our corpus construction and annotation methodology will be of value to others seeking to build high-quality semantically annotated corpora in biomedical domains.
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Almacenamiento y Recuperación de la Información/métodos , Registros Médicos , Procesamiento de Lenguaje Natural , Semántica , Indización y Redacción de Resúmenes , Investigación Biomédica , Guías como Asunto , Humanos , Internet , Modelos Estadísticos , Neoplasias , Terminología como Asunto , Interfaz Usuario-ComputadorRESUMEN
Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.
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Factor Neurotrófico Derivado del Encéfalo/genética , Disfunción Cognitiva/genética , Enfermedad de Parkinson/genética , Enfermedad de Alzheimer/complicaciones , Estudios de Casos y Controles , Disfunción Cognitiva/complicaciones , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Oportunidad Relativa , Enfermedad de Parkinson/complicaciones , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Población BlancaRESUMEN
Partial flattening of the spatially extended molecular scaffold has been employed as an effective tactic to improve the device performance of a perylenediimide (PDI)-based small-molecule acceptor because the less twisted yet not completely planar molecular geometry is anticipated to improve the molecular packing and thereby attain a more suitable balance between the carrier transport ability and phase domain size. A small-molecule acceptor BF-PDI comprising four α-substituted PDI units attached around a 9,9'-bifluorenylidene (BF) central moiety is designed and studied in polymer solar cells. The BF group is deemed a ring-fused analogue of the tetraphenylethylene (TPE) unit. Due to the less twisted and better conjugated BF skeleton, BF-PDI displays more delocalized lowest unoccupied molecular orbital. By virtue of both the electronic and steric effects, BF-PDI is suggested to bring about superior intermolecular stacking and donor-acceptor phase separation morphology in blend films. Indeed, the experimental results show that BF-PDI displays improved charge transport ability and a higher power-conversion efficiency of 8.05% than that of TPE-PDI. Grazing-incidence wide-angle X-ray diffraction and resonant soft X-ray scattering confirm the more compact and ordered molecular packing as well as smaller domain sizes in the P3TEA/BF-PDI blend.
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BACKGROUND: The Clinical E-Science Framework (CLEF) project has built a system to extract clinically significant information from the textual component of medical records in order to support clinical research, evidence-based healthcare and genotype-meets-phenotype informatics. One part of this system is the identification of relationships between clinically important entities in the text. Typical approaches to relationship extraction in this domain have used full parses, domain-specific grammars, and large knowledge bases encoding domain knowledge. In other areas of biomedical NLP, statistical machine learning (ML) approaches are now routinely applied to relationship extraction. We report on the novel application of these statistical techniques to the extraction of clinical relationships. RESULTS: We have designed and implemented an ML-based system for relation extraction, using support vector machines, and trained and tested it on a corpus of oncology narratives hand-annotated with clinically important relationships. Over a class of seven relation types, the system achieves an average F1 score of 72%, only slightly behind an indicative measure of human inter annotator agreement on the same task. We investigate the effectiveness of different features for this task, how extraction performance varies between inter- and intra-sentential relationships, and examine the amount of training data needed to learn various relationships. CONCLUSION: We have shown that it is possible to extract important clinical relationships from text, using supervised statistical ML techniques, at levels of accuracy approaching those of human annotators. Given the importance of relation extraction as an enabling technology for text mining and given also the ready adaptability of systems based on our supervised learning approach to other clinical relationship extraction tasks, this result has significance for clinical text mining more generally, though further work to confirm our encouraging results should be carried out on a larger sample of narratives and relationship types.
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Almacenamiento y Recuperación de la Información/métodos , Procesamiento de Lenguaje Natural , Algoritmos , Humanos , Sistemas de Registros Médicos ComputarizadosRESUMEN
BACKGROUND: Like text in other domains, biomedical documents contain a range of terms with more than one possible meaning. These ambiguities form a significant obstacle to the automatic processing of biomedical texts. Previous approaches to resolving this problem have made use of various sources of information including linguistic features of the context in which the ambiguous term is used and domain-specific resources, such as UMLS. MATERIALS AND METHODS: We compare various sources of information including ones which have been previously used and a novel one: MeSH terms. Evaluation is carried out using a standard test set (the NLM-WSD corpus). RESULTS: The best performance is obtained using a combination of linguistic features and MeSH terms. Performance of our system exceeds previously published results for systems evaluated using the same data set. CONCLUSION: Disambiguation of biomedical terms benefits from the use of information from a variety of sources. In particular, MeSH terms have proved to be useful and should be used if available.
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Documentación/métodos , Almacenamiento y Recuperación de la Información , Medical Subject Headings , Reconocimiento de Normas Patrones Automatizadas/métodos , Terminología como Asunto , Algoritmos , Inteligencia Artificial , Bases de Datos Bibliográficas , Lingüística , MEDLINE , Procesamiento de Lenguaje Natural , Unified Medical Language SystemRESUMEN
In this study, polymorphism in the bovine LEPR gene exon 4 was detected by PCR-SSCP and DNA sequencing methods in 653 individuals from five Chinese cattle breeds. Two haplotypes (M and N), three observed genotypes (MM, MN, and NN), and five single nucleotide polymorphisms (SNPs) (NC_007301:g.26767T>C, NC_007301:g.26805C>T, NC_007301:g.27050A>G, NC_007301:g.27063G>A, NC_007301:g.27079G>A) were detected. The frequencies of haplotypes M and N in the five breeds were 0.661-0.747 and 0.253-0.339, respectively. The SNP locus was in Hardy-Weinberg equilibrium in Nanyang, Jiaxian red, Angus, and Jinnan cattle (P > 0.05) and was in Hardy-Weinberg disequilibrium in Qinchuan cattle (P < 0.05). Polymorphism of the LEPR gene was shown to be associated with growth traits in the Nanyang breed. The SNP in the bovine LEPR gene had significant effects on body height, body length, body weight, heart girth, and average daily gain at 6 and 12 months old (P < 0.01 or P < 0.05). Therefore, these results suggest that the LEPR gene is a strong candidate gene that affects growth traits in cattle.
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Bovinos/crecimiento & desarrollo , Bovinos/genética , Polimorfismo de Nucleótido Simple , Receptores de Leptina/genética , Animales , Secuencia de Bases , Composición Corporal/genética , Cruzamiento , Exones , Haplotipos , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
The main function of ZAG gene is to enable the decomposition of fat, and reduced fat content. In this study, polymorphisms of four loci (Z1, Z2, Z3, Z4) at the coding region of the bovine ZAG gene were detected in 145 Jiaxian red cattle, and polymorphisms were found on Z1, Z3, Z4 loci. The fragments showing different SSCP patterns were sequenced, nd a total of six SNPs (C115T, A3257G, A4013G, T4027C, C4032T, and T4120C) were found. The Z3 locus of ZAG gene was at Hardy-Weinberg equilibrium, while Z1 and Z4 loci of ZAG gene were not at Hardy-Weinberg disequilibrium. The association analysis of different genotypes with some of the growth and development traits showed that the individuals with genotype AC had a larger body length, heart girth, circumference of cannon bone, body weight than the individuals with genotypes AA and AB (P<0.05 or P<0.01, respectively) in Z4 locus. It is suggest that Z4 locus may be one of the marker-assisted selection used as growth traits in Jiaxian red cattle.
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Bovinos/crecimiento & desarrollo , Bovinos/genética , Polimorfismo Genético , Proteínas de Plasma Seminal/genética , Animales , Pesos y Medidas Corporales , Cruzamiento , Bovinos/anatomía & histología , Exones/genética , Marcadores Genéticos/genética , Variación Genética , Genotipo , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Zn-alfa-2-GlicoproteínaRESUMEN
Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor growth and relapse in colorectal cancer (CRC), and therefore, they are promising targets for cancer therapy. Epidemiological evidence has suggested that the daily use of aspirin reduces overall mortality of CRC and the risk of distant metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC. Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell model and patient samples. Chemically modified aspirin and immunoprecipitation were adopted to detect the target proteins of aspirin. A locus-specific light-inducible epigenetic modification system based on CRISPR technology was constructed to verify the causal relationship in these molecular events. In vivo characterization was performed in a xenograft model. Results: We found that aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor progression, and enhances the anti-neoplastic effects of chemotherapeutic agents. Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9 acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs. Notably, these effects of aspirin are absent in non-CSCs since H3K9 is hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant therapy. Conclusions: Taken together, we revealed a unique epigenetic and cox-independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates colorectal CSCs. These findings establish an innovative framework of the therapeutic significance of aspirin.
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Antineoplásicos/metabolismo , Apoptosis , Aspirina/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Proteína Ligando Fas/metabolismo , Histonas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Acetilación , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Modelos Teóricos , Procesamiento Proteico-PostraduccionalRESUMEN
A new polymer acceptor, naphthodiperylenetetraimide-vinylene (NDP-V), featuring a backbone of altenating naphthodiperylenetetraimide and vinylene units is designed and applied in all-polymer solar cells (all-PSCs). With this polymer acceptor, a new record power-conversion efficiencies (PCE) of 8.59% has been achieved for all-PSCs. The design principle of NDP-V is to reduce the conformational disorder in the backbone of a previously developed high-performance acceptor, PDI-V, a perylenediimide-vinylene polymer. The chemical modifications result in favorable changes to the molecular packing behaviors of the acceptor and improved morphology of the donor-acceptor (PTB7-Th:NDP-V) blend, which is evidenced by the enhanced hole and electron transport abilities of the active layer. Moreover, the stronger absorption of NDP-V in the shorter-wavelength range offers a better complement to the donor. All these factors contribute to a short-circuit current density (J sc ) of 17.07 mA cm-2 . With a fill factor (FF) of 0.67, an average PCE of 8.48% is obtained, representing the highest value thus far reported for all-PSCs.