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Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association framework with no requirement of a priori knowledge of gene function. After creating this tool, we used it to test associations between gene expression profiles and two biological traits in single-gene deletion budding yeast mutants, including transcription homeostasis during S phase and global protein turnover. For each trait, we discovered novel regulators without prior functional annotations. The functional effects of the novel candidates were then validated experimentally, providing solid evidence for their roles in the respective traits. Hence, we conclude that iTARGEX can reliably identify novel factors involved in given biological traits. As such, it is capable of converting genome-wide observations into causal gene function predictions. Further application of iTARGEX in other contexts is expected to facilitate the discovery of new regulators and provide observations for novel mechanistic hypotheses regarding different biological traits and phenotypes.
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Perfilación de la Expresión Génica , Genes Reguladores , Proteolisis , Fase S/genética , Programas Informáticos , Transcripción Genética , Proteínas Portadoras/genética , Biología Computacional/métodos , Replicación del ADN , Eliminación de Gen , Homeostasis , Mutación , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
BACKGROUND: Many long non-coding RNAs (lncRNAs) have been extensively identified in higher eukaryotic species. The function of lncRNAs has been reported to play important roles in diverse biological processes, including developmental regulation and behavioral plasticity. However, there are no reports of systematic characterization of long non-coding RNAs in the fire ant Solenopsis invicta. RESULTS: In this study, we performed a genome-wide analysis of lncRNAs in the brains of S. invicta from RNA-seq. In total, 1,393 novel lncRNA transcripts were identified in the fire ant. In contrast to the annotated lncRNA transcripts having at least two exons, novel lncRNAs are monoexonic transcripts with a shorter length. Besides, the transcriptome from virgin alate and dealate mated queens were analyzed and compared. The results showed 295 differentially expressed mRNA genes (DEGs) and 65 differentially expressed lncRNA genes (DELs) between virgin and mated queens, of which 17 lncRNAs were highly expressed in the virgin alates and 47 lncRNAs were highly expressed in the mated dealates. By identifying the DEL:DEG pairs with a high association in their expression (Spearman's |rho|> 0.8 and p-value < 0.01), many DELs were co-regulated with DEGs after mating. Furthermore, several remarkable lncRNAs (MSTRG.6523, MSTRG.588, and nc909) that were found to associate with particular coding genes may play important roles in the regulation of brain gene expression in reproductive transition in fire ants. CONCLUSION: This study provides the first genome-wide identification of S. invicta lncRNAs in the brains in different reproductive states. It will contribute to a fuller understanding of the transcriptional regulation underpinning reproductive changes.
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Hormigas , ARN Largo no Codificante , Animales , Hormigas/genética , Encéfalo/metabolismo , Femenino , Perfilación de la Expresión Génica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , TranscriptomaRESUMEN
OBJECTIVE: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. METHODS: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. RESULTS: Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). CONCLUSION: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.
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BACKGROUND: Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer. METHODS: This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers). RESULTS: We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05). CONCLUSION: Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk.
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Medicamentos Herbarios Chinos , Humanos , Estudios de Cohortes , Medicamentos Herbarios Chinos/uso terapéutico , Taiwán , Recurrencia Local de Neoplasia , Medicina Tradicional ChinaRESUMEN
BACKGROUND: Current tuberculosis (TB) reporting protocols are insufficient to achieve the goals established by the Stop TB partnership. Some countries have recommended implementation of active case finding program. We assessed the effect of Cough Officer Screening (an active screening system) on the rate of TB detection and health care system delays over the course of four years. METHODS: Patients who were hospitalized at the Changhua Christian Hospital (Changhua, Taiwan) were enrolled from September 2004 to July 2006 (Stage I) and August 2006 to August 2008 (Stage II). Stage II was implemented after a Plan-Do-Check-Act (PDCA) cycle analysis indicated that we should exclude ICU and paediatric patients. RESULTS: In Stage I, our COS system alerted physicians to 19,836 patients, and 7,998 were examined. 184 of these 7,998 patients (2.3%) had TB. Among these 184 patients, 142 (77.2%) were examined for TB before COS alarming and 42 were diagnosed after COS alarming. In Stage II, a total of 11,323 patients were alerted by the COS system. Among them, 6,221 patients were examined by physicians, and 125 of these patients (2.0%) had TB. Among these 125 patients, 113 (90.4%) were examined for TB before COS alarming and 12 were diagnosed after COS alarming. The median time from COS alarm to clinical action was significantly less (p = 0.041) for Stage I (1 day; range: 0-16 days) than for Stage II (2 days; range: 0-10 days). CONCLUSION: Our COS system improves detection of TB by reducing the delay from infection to diagnosis. Modifications of scope may be needed to improve cost-effectiveness.
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Tos/etiología , Tamizaje Masivo/normas , Garantía de la Calidad de Atención de Salud , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico , Anciano , Anciano de 80 o más Años , Hospitales Públicos/estadística & datos numéricos , Humanos , Pacientes Internos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Modelos Organizacionales , Estudios Retrospectivos , Esputo/citología , Esputo/microbiología , Taiwán , Factores de TiempoRESUMEN
The purpose of the study was to examine the moderating effect of business role model and fear of failure on the relationship between entrepreneurial intention and behavior. The participants were sampled from 1865 college students who graduated from universities in China from 2012 to 2018. The experimental instrument was comprised of four scales concerning entrepreneurial intention, entrepreneurial behavior, fear of failure, and business role model. The data were analyzed using hierarchical regression. The results showed that: (1) Entrepreneurial intention was positively influenced the entrepreneurial behavior; (2) Fear of failure weakened the relationship between entrepreneurial intention and action; (3) The moderating effect of business role model on entrepreneurial intention and behavior was confirmed. We concluded that entrepreneurial intention was positively related to the entrepreneurial behavior, fear of failure hindered college students from taking entrepreneurial behavior, and business role model will enhance their entrepreneurial intention. The paper suggest that some measures should be taken to overcome college students' fear of failure, and to improve the education system of entrepreneurship in order to cultivate talents with creativity.
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Intellectual capital (IC) and corporate social responsibility (CSR) provide a strong link between the enterprise and stakeholders. These strategic approaches are responsible in value formation for better financial performance. This study investigates the mediating effects of corporate financial performance on the relationship between IC components (ICs) and CSR of firms from the food industry in Asia. We analyzed 308 firm-year observations of 44 listed firms from 2011 to 2017. The results of this study provided mixed findings regarding the effects of ICs and CSR. In addition, results vary from the disaggregated effects of each IC component on environmental, social, and governance pillars. The results also indicate that the combination of accounting and market-based estimates of financial performance was found to be significant mediating factor to explain the phenomenon which varies per ICs and dimensions of CSR. Lastly, the implications for sustainable business practices and investments in knowledge-based resources in the food industry are elaborated.
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Industria de Alimentos/organización & administración , Responsabilidad Social , Asia , Comercio , Humanos , Inversiones en SaludRESUMEN
BACKGROUND: The current Western medicine treatment options for benign prostatic hyperplasia (BPH) have various degrees of documented effectiveness. However, the uses of these interventions are limited to specific patient populations or have certain side effects that interfere with patient quality of life. This study evaluated the clinical effects of a Chinese herbal medicine (CHM) on patients with BPH. METHODS: This was a single-arm pilot study. Twenty BPH patients were enrolled, and they were required to take the investigated CHM three times a day for 8 weeks, along with their Western medicine. Patients returned to clinics as scheduled and completing international prostate symptoms scores (IPSS), aging male symptoms score, international index of erectile function, and body constitution questionnaire of traditional Chinese medicine. Uroflowmetry and sonography were also applied to evaluate the changes in urinary velocity and post-voiding residual urine volume from the baseline to the end of the study. RESULTS: The mean IPSS total score was significantly decreased by 2.5 points after 8 weeks of treatment with the CHM (from 17.5 to 15.0, p = 0.03). The mean IPSS voiding subscore was decreased by 1.7 points (from 10.1 to 8.4, p = 0.02), and the mean incomplete emptying subscore was decreased by 0.8 points (from 2.9 to 2.1, p = 0.02), with both decreases being statistically significant. A descending trend in the post-voiding residual urine volume was also observed (from 52.9 to 30.8 mL, p = 0.07). CONCLUSION: This trial indicated that the add-on CHM treatment (VGHBPH0) might be a potential treatment for improving the lower urinary tract symptoms of BPH patients.
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Medicamentos Herbarios Chinos/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Transcription-replication conflicts (TRCs) occur when intensive transcriptional activity compromises replication fork stability, potentially leading to gene mutations. Transcription-deposited H3K4 methylation (H3K4me) is associated with regions that are susceptible to TRCs; however, the interplay between H3K4me and TRCs is unknown. Here we show that H3K4me aggravates TRC-induced replication failure in checkpoint-defective cells, and the presence of methylated H3K4 slows down ongoing replication. Both S-phase checkpoint activity and H3K4me are crucial for faithful DNA synthesis under replication stress, especially in highly transcribed regions where the presence of H3K4me is highest and TRCs most often occur. H3K4me mitigates TRCs by decelerating ongoing replication, analogous to how speed bumps slow down cars. These findings establish the concept that H3K4me defines the transcriptional status of a genomic region and defends the genome from TRC-mediated replication stress and instability.
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Replicación del ADN , Histonas/metabolismo , Transcripción Genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quinasa de Punto de Control 2/genética , Quinasa de Punto de Control 2/metabolismo , Cromatina/metabolismo , ADN Polimerasa II/metabolismo , Genoma Fúngico/genética , Inestabilidad Genómica , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/genética , Metilación , Modelos Genéticos , Mutación , Puntos de Control de la Fase S del Ciclo Celular/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
New-generation farmers have become a vital force for entrepreneurship in their hometowns. To better promote farmers to start businesses, it's important to know about their quality of work life. Based on a survey of the quality of work life and entrepreneurship will of farmers from three cities and eight counties in Shandong province of China, this paper analyzed the effects of farmers' quality of work life on their entrepreneurship will in their hometowns using a Logistic regression model. Our findings show that farmers have a relatively low cognition level of their quality of work life, and their interpersonal relationship, work characteristics, material security, and family demands have significant effects on their entrepreneurship will. According to the findings, this paper proposed some suggestions for promoting farmers' entrepreneurship will in their hometowns from the perspectives of organizational management, extrinsic entrepreneurship stimulus, and internal demand.
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Entrepreneurship research has been focusing on intangible capitals of an entrepreneur or entrepreneurial teams. Intellectual capital has been a useful framework for researching entrepreneurship, though the inclusion of intangible capital has not been comprehensive enough. We followed and extended this stream to add psychological capital into the discussion of the relationship between intellectual capital and new venture performance. We argue that psychological capital, human capital, and relational capital are representative capitals of entrepreneurs at intra-personal, personal, and interpersonal levels, respectively, none of them can be neglected for new venture success. Based on the analyses of documentary materials of famous entrepreneurs' interviews from trustable websites/media, this conceptual analyses with case examples found different constructs to serve as important entrepreneurial intellectual capital, which consists of human (i.e., age and education, graduate work experiences, non-graduate work experiences, role models), relational (i.e., trustworthiness and co-founder relations) capitals, and psychological capital (optimism, self-efficacy, hope, and strength). This study contributes by formalizing psychological capital as a theoretical element of intellectual capital and its effectiveness with other forms of intellectual capital on entrepreneurial performance and growth.
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BACKGROUND: Since Taiwan's national health insurance system provides residents with easy and affordable access to clinical acupuncture treatment, this study sought to analyze trends in the publication of acupuncture-related research in Taiwan from 1988 to 2017, using a bibliometric method. METHODS: Data on the scholarly literature from 1988 to 2017 were retrieved through Web of Science searches for the keywords acupunct*, acupoint*, electroacupunct*, electro-acupunct*, acupre*, auricular acupunc*, and auricular needle* in study titles. RESULTS: A total of 539 acupuncture-related articles published from 1988 to 2017 were identified and analyzed. The articles had an h-index of 38 and were cited in subsequent studies 7250 times, meaning that Taiwan ranked sixth in the production of such publications among countries/regions globally. Among those articles, 99 (18.4%) had no subsequent citations, six (1.1%) were highly cited (over 100 citations), and 141 (26.1%) were cited 4 to 10 times. The highly cited articles discussed the possible pathways of acupuncture stimulation and efficacy, and received 1103 (15.2%) of the citations. CONCLUSION: The China Medical University in Taichung, Taiwan, was the most active educational institution in Taiwan in terms of acupuncture-related research. Professor Lin Jaung-Geng was the leading acupuncture-related researcher, having the most publications, citations, and the highest h-index value. These results provided a context for analyzing the strengths of the existing research and informing prospective strategies for further studies.
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Terapia por Acupuntura , Bibliometría , Investigación Biomédica , Humanos , Medicina Tradicional China , Publicaciones , Taiwán , Factores de TiempoRESUMEN
For decades, professional divisions have been represented as the main structural divisions in Western medicine throughout the world. In Taiwan, medical policymakers are also interested in designing professional divisions of traditional Chinese medicine (TCM). Therefore, this study evaluated the current status and potentiality of professional divisions of TCM in Taiwan using data from the year 2012 obtained from the National Health Insurance Research Database; the database provides information regarding age and gender of TCM physicians (TCMPs); total visit counts; contracted medical institution codes; groupings of diseases classified under International Classification of Diseases, Ninth Revision, Clinical Modification codes; numbers of children and female patients seeking treatment; and claim disposition codes used by each TCMP. The results indicated that there were 5522 TCMPs in 2012, and 4876 (90.3%) TCMPs practiced in primary clinics. The proportions of pediatric visits to these TCMPs were mostly below 0.2, and acupuncture or traumatology-related visit proportions were below 0.5. Only a few of the studied Taiwan-based TCMPs practiced gynecology and pediatrics, but most of them performed "internal medicine", or "acupuncture" or "traumatology" treatments. Thus, the number of TCM specialists practicing gynecology or pediatrics is insufficient, indicating that a policy that forms professional divisions of TCM practitioners in Taiwan should be reconsidered.
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Medicina Tradicional China , Médicos , Terapia por Acupuntura , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Ginecología , Humanos , Medicina Interna , Masculino , Registros Médicos , Persona de Mediana Edad , Programas Nacionales de Salud , Pediatría , TaiwánRESUMEN
In this article, we present a new paradigm for organometallic hybrid perovskite solar cell using NiO inorganic metal oxide nanocrystalline as p-type electrode material and realized the first mesoscopic NiO/perovskite/[6,6]-phenyl C61-butyric acid methyl ester (PC61BM) heterojunction photovoltaic device. The photo-induced transient absorption spectroscopy results verified that the architecture is an effective p-type sensitized junction, which is the first inorganic p-type, metal oxide contact material for perovskite-based solar cell. Power conversion efficiency of 9.51% was achieved under AM 1.5 G illumination, which significantly surpassed the reported conventional p-type dye-sensitized solar cells. The replacement of the organic hole transport materials by a p-type metal oxide has the advantages to provide robust device architecture for further development of all-inorganic perovskite-based thin-film solar cells and tandem photovoltaics.
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Next-Generation-Sequencing is advantageous because of its much higher data throughput and much lower cost compared with the traditional Sanger method. However, NGS reads are shorter than Sanger reads, making de novo genome assembly very challenging. Because genome assembly is essential for all downstream biological studies, great efforts have been made to enhance the completeness of genome assembly, which requires the presence of long reads or long distance information. To improve de novo genome assembly, we develop a computational program, ARF-PE, to increase the length of Illumina reads. ARF-PE takes as input Illumina paired-end (PE) reads and recovers the original DNA fragments from which two ends the paired reads are obtained. On the PE data of four bacteria, ARF-PE recovered >87% of the DNA fragments and achieved >98% of perfect DNA fragment recovery. Using Velvet, SOAPdenovo, Newbler, and CABOG, we evaluated the benefits of recovered DNA fragments to genome assembly. For all four bacteria, the recovered DNA fragments increased the assembly contiguity. For example, the N50 lengths of the P. brasiliensis contigs assembled by SOAPdenovo and Newbler increased from 80,524 bp to 166,573 bp and from 80,655 bp to 193,388 bp, respectively. ARF-PE also increased assembly accuracy in many cases. On the PE data of two fungi and a human chromosome, ARF-PE doubled and tripled the N50 length. However, the assembly accuracies dropped, but still remained >91%. In general, ARF-PE can increase both assembly contiguity and accuracy for bacterial genomes. For complex eukaryotic genomes, ARF-PE is promising because it raises assembly contiguity. But future error correction is needed for ARF-PE to also increase the assembly accuracy. ARF-PE is freely available at http://140.116.235.124/~tliu/arf-pe/.
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Genoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Animales , Bacterias/genética , Hongos/genética , Genoma Bacteriano/genética , HumanosRESUMEN
BACKGROUND: The radiological manifestations of lower lung field (LLF) tuberculosis (LLFTB) are similar to those of LLF pneumonia (LLFP), making diagnosis challenging. The aim of this study was to determine if there are differences in the clinical manifestations of LLFTB and LLFP in patients with unilateral LLF opacities. METHODS: We performed a retrospective review of patient records to identify those with unilateral LLF opacities who were subsequently diagnosed with LLFTB or LLFP. We compared demographics, clinical manifestations, hematological data, and radiographic findings between the groups of patients. RESULTS: We identified 22 and 72 patients diagnosed with LLFTB and LLFP, respectively. Multivariate analysis revealed that age (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.99-1.11, P=0.072), lack of fever>38°C (OR=9.04, 95% CI=1.69-48.40, P=0.001), duration of symptoms≥7 days (OR=4.57, 95% CI=1.09-19.26, P=0.038), and the lack of air bronchograms upon radiography (OR=12.08, 95% CI=1.98-73.64, P=0.007) were significant predictors of LLFTB in patients with LLF opacities. We used these predictors to construct a mathematical model for predicting LLFTB in patients with LLF opacities. CONCLUSIONS: Our findings suggest that older age, prolonged duration of symptoms, lack of fever>38°C, and the absence of air bronchograms are more common in patients with LLFTB than patients with LLFP. These findings may help clinicians differentiate between LLFTB and LLFP and thus initiate timely and appropriate treatment.
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Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Neumonía/epidemiología , Radiografía Torácica/estadística & datos numéricos , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/epidemiología , Anciano , China/epidemiología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Neumonía/terapia , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Factores de Riesgo , Sensibilidad y Especificidad , Tuberculosis Pulmonar/terapiaRESUMEN
To understand the effect of photosensitizer (PS) release from graft copolymer based micelles in photodynamic therapy (PDT), the two pH-sensitive and non-pH-sensitive graft copolymers, (poly(N-vinyly caprolactam)-g-poly(D,L-lactide) and poly(N-vinyly caprolactam-co-N-vinyl imidazole)-g-poly(D,L-lactide)), were synthesized and utilized for the encapsulation of protoporphyrin IX (PPIX) for in vitro and in vivo PDT studies. Photochemical internalization (PCI) was utilized to study the localization of pH- and non-pH-sensitive micelles uptake in the lysosome. After non-toxic light treatment, PPIX was found in the nucleus with pH-sensitive micelles, while PPIX was still localized in the lysosomal organism with the non-pH-sensitive micelles, as observed by confocal microscopy. Because the formation of singlet oxygen was observed for the block and graft micelles, dramatic differences in the cell viability could be ascribed to the damage occurring at the region where the PPIX was located. An in vivo study revealed that PPIX-loaded graft and diblock micelles presented prolonged blood circulation and enhanced tumor targeting ability. The PPIX released from g-CIM micelles on tumor site was further proved by ex vivo confocal image. In addition, non-pH-sensitive micelle-treated mice showed a better repression of tumor growth than PPIX-treated mice, which was likely due to the larger amount of PS localized in the tumor region still exhibiting therapeutic effects. Finally, effective PDT-induced inhibition of tumor growth was found in pH-sensitive micelle-treated mice. This work provides insight into PS-loaded graft and diblock micelles for the PDT of tumors.
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Micelas , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Animales , Línea Celular Tumoral , Núcleo Celular/metabolismo , Femenino , Humanos , Concentración de Iones de Hidrógeno , Luz , Lisosomas/química , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión/métodos , Modelos Químicos , Trasplante de Neoplasias , Oxígeno/química , Fotoquímica/métodos , Polímeros/química , Protoporfirinas/química , Factores de TiempoRESUMEN
A cerebellar model articulation controller (CMAC) control system, which contains only one single-input controller implemented by a differentiable CMAC, is proposed in this paper. In the proposed scheme, the CMAC controller is solely used to control the plant, and no conventional controller is needed. Without a preliminary offline learning, the single-input CMAC controller can provide the control effort to the plant at each online learning step. To train the differentiable CMAC online, the gradient descent algorithm is employed to derive the learning rules. The sensitivity of the plant, with respect to the input, is approximated by a simple formula so that the learning rules can be applied to unknown plants. Moreover, based on a discrete-type Lyapunov function, conditions on the learning rates guaranteeing the convergence of the output error are derived in this paper. Finally, simulations on controlling three different plants are given to demonstrate the effectiveness of the proposed controller.
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Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g-PLA and diblock copolymer PEG-PLA with functional moiety was developed in this study. The mixed micelles had well defined core shell structure which was evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA exhibited pH stimulate to enable intracellular drug delivery and outer shell of PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate for cancer specific targeting were synthesized at the end of the polymer chain. The graft and diblock copolymer self assembled to nanospheres against water with an average diameter below 120 nm without doxorubicin, and an average diameter of around 200 nm when loaded with drug. From drug released study, a change in pH destroy the inner core to lead a significant doxorubicin(Dox) release from mixed micelles. Cellular uptake of folate-micelles was found to be higher than that of non-folate-micelles due to the folate-binding effect on the cell membrane, thereby providing a similar cytotoxic effect to drug only against the HeLa cell line. In vivo study revealed that specific targeting of folate-micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate-PEG-PLA have great potential in cancer chemotherapy and diagnosis.
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Micelas , Neoplasias/tratamiento farmacológico , Polímeros , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapéutico , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Ácido Fólico/química , Ácido Fólico/metabolismo , Células HeLa , Humanos , Ratones , Estructura Molecular , Trasplante de Neoplasias , Polímeros/química , Polímeros/uso terapéutico , Distribución TisularRESUMEN
Mixed micelles formed by critical micelle concentration (Cmc) character's diblock copolymer, and temperature-sensitive character's diblock copolymer were studied for their capabilities in improving stability with and without drug. Experimental results showed that this type of mixed micellar systems possessed complementary effects in adjusting external temperature shift (storage vs. body temperature) and concentration change (dilution after intravenous injection). Therefore, they provided excellent stability as drug carriers. Further results obtained from physicochemical property and drug release kinetics studies demonstrated such systems could also be applied to physiological conditions, in compliance with varied pH environments. We concluded that the newly developed mixed micelles can serve as a potential injectable drug delivery system for anticancer drugs, such as doxorubicin and many others.