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DNA polymerase stalling activates the ATR checkpoint kinase, which in turn suppresses fork collapse and breakage. Herein, we describe use of ATR inhibition (ATRi) as a means to identify genomic sites of problematic DNA replication in murine and human cells. Over 500 high-resolution ATR-dependent sites were ascertained using two distinct methods: replication protein A (RPA)-chromatin immunoprecipitation (ChIP) and breaks identified by TdT labeling (BrITL). The genomic feature most strongly associated with ATR dependence was repetitive DNA that exhibited high structure-forming potential. Repeats most reliant on ATR for stability included structure-forming microsatellites, inverted retroelement repeats, and quasi-palindromic AT-rich repeats. Notably, these distinct categories of repeats differed in the structures they formed and their ability to stimulate RPA accumulation and breakage, implying that the causes and character of replication fork collapse under ATR inhibition can vary in a DNA-structure-specific manner. Collectively, these studies identify key sources of endogenous replication stress that rely on ATR for stability.
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Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Proteínas de la Ataxia Telangiectasia Mutada/genética , Replicación del ADN/genética , Repeticiones de Microsatélite/genética , Animales , Proteínas de Ciclo Celular/genética , Cromatina/genética , Inmunoprecipitación de Cromatina/métodos , Roturas del ADN de Doble Cadena , Daño del ADN/genética , Femenino , Inestabilidad Genómica/genética , Humanos , Ratones , Proteína de Replicación A/genéticaRESUMEN
Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.
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Eliminación de Componentes Sanguíneos , Reacción a la Transfusión , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Plaquetas , Eliminación de Componentes Sanguíneos/efectos adversos , Transfusión de Plaquetas/efectos adversosRESUMEN
BACKGROUND: Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. RESULTS: Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45-74%]) and 78% (95% CI [69-86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86-10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26-83%]) and 75% (95% CI [68-82%]), and those for CRP were 67% (95% CI [35-88%]) and 73% (95% CI [69-77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93). CONCLUSION: While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.
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Neoplasias Hematológicas , Neoplasias , Adulto , Humanos , Polipéptido alfa Relacionado con Calcitonina , Neoplasias/complicaciones , Neoplasias Hematológicas/complicaciones , Proteína C-Reactiva , Oportunidad RelativaRESUMEN
Strain Lactiplantibacillus plantarum D1 with bacteriocin producing ability was found in the intestine of Gambusia affinis. The bacteriocin was found to have high inhibitory activity against multiple Streptococcus species and several other Gram-positive and Gram-negative bacteria. Bacteriocin was purified from culture supernatant by ion-exchange chromatography, Sep-Pak C18 cartridge, and reverse-phase high-performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectral analysis determined that purified bacteriocin has a molecular mass of 2,731 Da. A partial N-terminal sequence KRKKHKXQIYNNGM was obtained from the Edman analysis. The N-terminal sequence was employed to search against a translation of the draft genome of strain D1. The translated full amino acid sequence of the mature peptide is as follows: NH2- KRKKHKCQIYNNGMPTGQYRWC, which has a molecular weight of 2738 Da. A BLAST search revealed that this bacteriocin was most similar to bactofencin A but differed from it with three amino acid residues. No identical peptide or protein has been previously reported, and this peptide, termed bactofencin YH, was therefore considered to be a new bacteriocin produced by Lactiplantibacillus plantarum D1.
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Secuencia de Aminoácidos , Antibacterianos , Bacteriocinas , Peso Molecular , Streptococcus , Bacteriocinas/farmacología , Bacteriocinas/química , Bacteriocinas/aislamiento & purificación , Bacteriocinas/metabolismo , Streptococcus/efectos de los fármacos , Streptococcus/genética , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Pruebas de Sensibilidad Microbiana , Animales , Cromatografía Líquida de Alta Presión , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacosRESUMEN
Background and Objectives: In patients with urolithiasis-related obstructive pyelonephritis (UROP), sepsis represents a critical and concerning complication that can substantially increase the mortality rate. This study aimed to identify the risk factors for sepsis in UROP patients and to develop a predictive nomogram model. Materials and Methods: We analyzed data from 148 patients who met the UROP criteria and were admitted to Chang Gung Memorial Hospital between 1 January 2016 and 31 December 2021. The primary outcome evaluated was the incidence of sepsis, as defined by the most recent Sepsis-3 guidelines. To identify potential risk factors for sepsis, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, we utilized multivariable logistic regression to construct the predictive model. Results: There was a total of 102 non-sepsis cases and 46 sepsis cases. Risk factors for sepsis in multivariable analysis were a history of diabetes mellitus (DM) (OR = 4.24, p = 0.007), shock index (SI) (×10-1) (OR = 1.55, p < 0.001), C-reactive protein (CRP) (mg/dL) (OR = 1.08, p = 0.005), and neutrophil to lymphocyte ratio (NLR) (×10) (OR = 1.58, p = 0.007). The nomogram exhibited an area under the receiver operating characteristic curve of 0.890 (95% CI 0.830-0.949). Conclusions: Our study demonstrated that patients with UROP who have DM, higher SI, higher NLR, and elevated CRP levels are significantly more likely to develop sepsis. These insights may aid in risk stratification, and it is imperative that clinicians promptly initiate treatment for those identified as high risk.
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Nomogramas , Pielonefritis , Sepsis , Urolitiasis , Humanos , Pielonefritis/complicaciones , Sepsis/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Urolitiasis/complicaciones , Anciano , Factores de Riesgo , Modelos Logísticos , Estudios Retrospectivos , Adulto , Taiwán/epidemiologíaRESUMEN
BACKGROUND/PURPOSE: Pulmonary alveolar proteinosis (PAP) is rare disease manifested as alveolar macrophage dysfunction and abnormal accumulation of surfactant protein in the alveoli. In this nationwide, population-based study, we investigated the epidemiology of PAP in Taiwan, and discovered the comorbidities and prognostic factors of PAP. METHODS: From the National Health Insurance Research Database (NHIRD), we obtained comprehensive information about all patients of PAP in Taiwan between 1995 and 2013. The incidence, baseline characteristics comorbidities, and prognostic factors of PAP were investigated. RESULTS: The annual incidence rate of PAP was around 0.79 (range: 0.49-1.17) patients per million people after 2000, and the prevalence rate was 7.96 patients per million people by the end of 2013. In total, 276 patients of PAP were identified, including 177 (64%) and 99 (36%) patients with primary and secondary PAP, respectively. The median age of diagnosis was 53.8 years. The median survival was 9.6 years after the initial PAP diagnosis, and the 5-year survival rate was 65.96%. Twenty (7%) patients received whole lung lavage (WLL) within three months after the diagnosis had significantly better survival compared to the others. Multivariable Cox regression analyses showed that elder age, secondary PAP, and malignancy were associated with poorer survival, while WLL within 3 months of diagnosis might greatly improve the survival. CONCLUSION: We demonstrated the epidemiology of PAP in Taiwan, showing several poor prognostic factors and the potential effectiveness of WLL. Further prospective studies based on registry are warranted to improve the diagnosis and treatment of PAP.
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Proteinosis Alveolar Pulmonar , Humanos , Anciano , Persona de Mediana Edad , Lactante , Proteinosis Alveolar Pulmonar/epidemiología , Proteinosis Alveolar Pulmonar/terapia , Proteinosis Alveolar Pulmonar/diagnóstico , Taiwán/epidemiología , Estudios Prospectivos , Lavado Broncoalveolar , Pulmón/patologíaRESUMEN
Secreted exosomal microRNAs (miRNAs) mediate interorgan/tissue communications by modulating target gene expression, thereby regulating developmental and physiological functions. However, the source, route, and function in target cells have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell-autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas the precursor form of miR-274 is expressed in glia, the mature form of miR-274 distributes broadly, including in synaptic boutons, muscle cells, and tracheal cells. Mature miR-274 is secreted from glia to the circulating hemolymph as an exosomal cargo, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. We further show that miR-274 can function in the neurons or tracheal cells to modulate the growth of synaptic boutons and tracheal branches, respectively. Also, miR-274 uptake into the target cells by AP-2-dependent mechanisms modulates target cell growth. In the target cells, miR-274 down-regulates Sprouty (Sty) through a targeting sequence at the sty 3' untranslated region, thereby enhancing MAPK signaling and promoting cell growth. miR-274 expressed in glia of an mir-274 null mutant is released as an exosomal cargo in the circulating hemolymph, and such glial-specific expression resets normal levels of Sty and MAPK signaling and modulates target cell growth. mir-274 mutant larvae are hypersensitive to hypoxia, which is suppressed by miR-274 expression in glia or by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.
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Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de la Membrana/genética , MicroARNs/metabolismo , Neuroglía/metabolismo , Regiones no Traducidas 3'/genética , Animales , Animales Modificados Genéticamente , Hipoxia de la Célula/genética , Regulación hacia Abajo , Exosomas/metabolismo , Femenino , Hemolinfa/metabolismo , Larva/crecimiento & desarrollo , Larva/metabolismo , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/genética , Mutación , Terminales Presinápticos/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Tráquea/crecimiento & desarrollo , Tráquea/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND/PURPOSE: This study aimed to analyze the long-term outcomes of hypofractionated whole-breast irradiation (WBI) (HF-WBI) compared with those of conventionally fractionated WBI (CF-WBI) for early breast cancer treated with breast-conservation surgery (BCS) and adjuvant WBI in Taiwan. METHODS: This study included patients treated at our institution between 2012 and 2016. All patients with early breast cancer received BCS (pT1-2, pN0, M0) and adjuvant WBI through one of two treatment schemes. Propensity score matching analysis was conducted to create comparable cohorts. The major result is ipsilateral breast tumor recurrence (IBTR) rates and overall survival rates. RESULTS: A total of 869 patients with early-stage breast cancer received adjuvant HF-WBI or CF-WBI were included. After matching, 718 patients were separated into two groups of the same number. With a median follow-up of 66 months, seven cases of IBTR were noted (three for CF, four for HF). There were no significant differences between the HF-WBI and CF-WBI groups in 5-year IBTR rates (0.9% vs 0.6%, P = 0.3887, 95% CI [0.25-7.79]) and 5-year overall survival rates (98.1% vs 98.9%, P = 0.4702, 95% CI [0.32-3.49]). In our institution, the use of HF-WBI increased significantly from 5% before 2012 (Q3) to 92% in 2016 (Q4). There was no significant difference in grade 1-2 toxicity between the two treatment groups. Fewer cases of grade 3 skin toxicity noted in the HF-WBI group (zero vs four events). CONCLUSION: HF-WBI had similar IBTR, OS and toxicity to CF-WBI.
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Neoplasias de la Mama , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/etiología , Radioterapia Adyuvante/efectos adversos , Taiwán/epidemiologíaRESUMEN
In this study, nanostructured gold was successfully prepared on a bare Au electrode using the electrochemical deposition method. Nanostructured gold provided more exposed active sites to facilitate the ion and electron transfer during the electrocatalytic reaction of organophosphorus pesticide (methyl parathion). The morphological and structural characterization of nanostructured gold was conducted using field-emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), which was further carried out to evaluate the electrocatalytic activity towards methyl parathion sensing. The electrochemical performance of nanostructured gold was investigated by electrochemical measurements (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)). The proposed nanostructured gold-modified electrode exhibited prominent electrochemical methyl parathion sensing performance (including two linear concentration ranges from 0.01 to 0.5 ppm (R2 = 0.993) and from 0.5 to 4 ppm (R2 = 0.996), limit of detection of 5.9 ppb, excellent selectivity and stability), and excellent capability in determination of pesticide residue in real fruit and vegetable samples (bok choy and strawberry). The study demonstrated that the presented approach to fabricate a nanostructured gold-modified electrode could be practically applied to detect pesticide residue in agricultural products via integrating the electrochemical and gas chromatography coupled with mass spectrometry (GC/MS-MS) analysis.
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Nanopartículas del Metal , Metil Paratión , Nanocompuestos , Residuos de Plaguicidas , Plaguicidas , Metil Paratión/análisis , Plaguicidas/análisis , Compuestos Organofosforados/análisis , Oro/química , Residuos de Plaguicidas/análisis , Nanocompuestos/química , Electrodos , Técnicas Electroquímicas/métodos , Límite de Detección , Nanopartículas del Metal/químicaRESUMEN
Morphologically tunable copper oxide-based nanomaterials on Cu wire have been synthesized through a one-step alkali-assisted surface oxidation process for non-enzymatic glucose sensing. Subsequently, copper oxide-based nanomaterials on Cu wire as a supporting matrix to deposit manganese oxide for the construction of heterostructured Mn-Cu bimetallic oxide architectures through spontaneous redox reaction in the KMnO4 solution for supercapacitors. Field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) confirmed that morphological and phase transformation from Cu(OH)2 to CuO occurred in copper oxide-based nanomaterials on Cu wire with different degrees of growth reaction. In non-enzymatic glucose sensing, morphologically tunable copper oxide-based nanomaterials owned the high tunability of electrocatalytically active sites and intrinsic catalytic activity to meet efficient glucose electrooxidation for obtaining promoted non-enzymatic glucose sensing performances (sensitivity of 2331 µA mM-1 cm-2 and the limit of detection of 0.02 mM). In the supercapacitor, heterostructured Mn-Cu bimetallic oxide-based nanomaterials delivered abundant redox-active sites and continuous conductive network to optimize the synergistic effect of Mn and Cu redox species for boosting the pseudo-capacitance performance (areal capacitance value of 79.4 mF cm-2 at 0.2 mA cm-2 current density and capacitance retention of 74.9% after 1000 cycles). It concluded that morphologically tunable copper oxide-based nanomaterials on Cu wire with/without deposition of manganese oxide could be good candidates for the future design of synergistic multifunctional materials in electrochemical techniques.
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Técnicas Biosensibles , Nanoestructuras , Cobre/química , Electrodos , Glucosa/química , Compuestos de Manganeso , ÓxidosRESUMEN
Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.
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Quinasa 1 de Adhesión Focal/fisiología , Neoplasias , Animales , Antineoplásicos/farmacología , Humanos , Neoplasias/metabolismo , Neoplasias/terapia , Microambiente TumoralRESUMEN
Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-ß/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.
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Infecciones Bacterianas/metabolismo , Drosophila/genética , Drosophila/microbiología , Transducción de Señal , Animales , Infecciones Bacterianas/genética , Proliferación Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Enterocitos/metabolismo , Femenino , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Intestinos/citología , Intestinos/microbiología , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Pectobacterium carotovorum/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Pseudomonas/metabolismo , Células Madre/microbiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Zn-Co-S ball-in-ball hollow sphere (BHS) was successfully prepared by solvothermal sulfurization method. An efficient strategy to synthesize Zn-Co-S BHS consisted of multilevel structures by controlling the ionic exchange reaction was applied to obtain great performance electrode material. Carbon nanotubes (CNTs) as a conductive agent were uniformly introduced with Zn-Co-S BHS to form Zn-Co-S BHS/CNTs and expedited the considerable electrocatalytic behavior toward glucose electro-oxidation in alkaline medium. In this study, characterization with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) was used for investigating the morphological and physical/chemical properties and further evaluating the feasibility of Zn-Co-S BHS/CNTs in non-enzymatic glucose sensing. Electrochemical methods (cyclic voltammetry (CV) and chronoamperometry (CA)) were performed to investigate the glucose sensing performance of Zn-Co-S BHS/CNTs. The synergistic effect of Faradaic redox couple species of Zn-Co-S BHS and unique conductive network of CNTs exhibited excellent electrochemical catalytic ability towards the glucose electro-oxidation, which revealed linear range from 5 to 100 µM with high sensitivity of 2734.4 µA mM-1 cm-2, excellent detection limit of 2.98 µM, and great selectivity in the presence of dopamine, uric acid, ascorbic acid, and fructose. Thus, Zn-Co-S BHS/CNTs would be expected to be a promising material for non-enzymatic glucose sensing.
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Técnicas Biosensibles , Técnicas Electroquímicas , Glucosa/análisis , Nanotubos de Carbono , Electrodos , ZincRESUMEN
AIM AND OBJECTIVES: This study aimed to explore the effects of person-centred care on their job productivity, job satisfaction and organisational commitment among employees in long-term care facilities. BACKGROUND: Person-centred care has been regarded as the best caregiving model for long-term care facilities. Few studies tested the impact of person-centred care on employee performance. DESIGN: A cross-sectional study was employed. METHODS: This study sent 373 samples with self-report questionnaires to the employees of sixteen long-term care facilities in Taiwan. A total of 366 valid samples were collected. A 33-item person-centred care questionnaire with Likert-scale responses was developed to assess the extent of person-centred care. We adopted hierarchical multiple regression analysis to test the impact of person-centred care on employee performance. We adopted the STROBE guidelines. RESULTS: Friendly environment level and personalised care, respectively, scored the highest with a mean of 4.19 among five dimensions of person-centred care. Personalised care, residents' self-realisation and relationships, and organisational support had significant positive correlations with job productivity. Friendly environment level and organisational support had significant correlations with job satisfaction. Friendly environment level, residents' self-realisation and relationships, and organisational support had significant correlations with organisational commitment. CONCLUSION: Person-centred care has beneficial impact on job satisfaction, job productivity and organisational commitment of employees in long-term care facilities. RELEVANCE TO CLINICAL PRACTICE: Person-centred care appears to be a crucial factor of employee performance in long-term care facilities. The five-dimensional person-centred care questionnaire in this study can serve as an important management tool for improving the effectiveness of person-centred care.
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Satisfacción en el Trabajo , Cuidados a Largo Plazo/normas , Atención Dirigida al Paciente/normas , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Instituciones de Cuidados Especializados de Enfermería/organización & administración , Encuestas y Cuestionarios , TaiwánRESUMEN
To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression) and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM)-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.
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Ciclo Celular/genética , Diferenciación Celular/genética , Proteínas de Drosophila/genética , Proteínas del Grupo Polycomb/genética , Factores de Transcripción/genética , Animales , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Cromatina/genética , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/biosíntesis , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Ojo/crecimiento & desarrollo , Ojo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Chaperonas de Histonas/biosíntesis , Chaperonas de Histonas/genética , Histonas/genética , Discos Imaginales/crecimiento & desarrollo , Discos Imaginales/metabolismo , Mutación , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Proteínas del Grupo Polycomb/biosíntesis , Factores de Transcripción/biosíntesisRESUMEN
Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway inflammatory diseases that share some common features, although these diseases are somewhat different in etiologies, clinical features, and treatment policies. The aim of this study is to investigate the common microRNA-mediated changes in bronchial epithelial cells of asthma and COPD. The microRNA profiles in primary bronchial epithelial cells from asthma (AHBE) and COPD (CHBE) patients and healthy subjects (NHBE) were analyzed with next-generation sequencing (NGS) and the significant microRNA changes common in AHBE and CHBE were extracted. The upregulation of hsa-miR-10a-5p and hsa-miR-146a-5p in both AHBE and CHBE was confirmed with quantitative polymerase chain reaction (qPCR). Using bioinformatic methods, we further identified putative targets of these microRNAs, which were downregulated in both AHBE and CHBE: miR-10a-5p might suppress BCL2, FGFR3, FOXO3, PDE4A, PDE4C, and PDE7A; miR-146a-5p might suppress BCL2, INSR, PDE4D, PDE7A, PDE7B, and PDE11A. We further validated significantly decreased expression levels of FOXO3 and PDE7A in AHBE and CHBE than in NHBE with qPCR. Increased serum miR-146a-5p level was also noted in patients with asthma and COPD as compared with normal control subjects. In summary, our study revealed possible mechanisms mediated by miR-10a-5p and miR-146a-5p in the pathogenesis of both asthma and COPD. The findings might provide a scientific basis for developing novel diagnostic and therapeutic strategies.
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Asma/genética , Bronquios/patología , Biología Computacional/métodos , Células Epiteliales/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , MicroARNs/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Anciano , Asma/sangre , Asma/patología , Femenino , Ontología de Genes , Humanos , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/patología , Regulación hacia Arriba/genéticaRESUMEN
AIMS: Develop the patient-centred innovation questionnaire for hospital nurses and establish its validity and reliability. BACKGROUND: Patient-centred care has been adopted by health care managers in their efforts to improve health care quality. It is regarded as a core concept for developing innovation. METHODS: A cross-sectional study was employed to collect data from hospital nurses in Taiwan. This study was divided into two stages: pilot study and main study. In the main study, 596 valid responses were collected. This study adopted reliability analysis, exploratory factor analysis, confirmatory factor analysis and selected nurse innovation scale as a criterion to test criterion-related validity. RESULTS: Five-dimension patient-centred innovation questionnaire was proposed: access and practicability, co-ordination and communication, sharing power and responsibility, care continuity, family and person focus. Each dimension demonstrated a reliability of 0.89-0.98. All dimensions had acceptable convergent and discriminate validity. The patient-centred innovation questionnaire and nurse innovation scale exhibited a significantly positive correlation. CONCLUSIONS: Patient-centred innovation questionnaire not only had a good theoretical basis but also had sufficient reliability and construct validity, and criterion-related validity. IMPLICATIONS FOR NURSING MANAGEMENT: Patient-centred innovation questionnaire could give a measure for evaluating the implementation of patient-centred care and could be used as a management tool during the process of nurse innovation.
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Enfermeras y Enfermeros/psicología , Atención Dirigida al Paciente/métodos , Psicometría/instrumentación , Psicometría/normas , Adulto , Estudios Transversales , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros/estadística & datos numéricos , Innovación Organizacional , Atención Dirigida al Paciente/normas , Atención Dirigida al Paciente/estadística & datos numéricos , Proyectos Piloto , Psicometría/estadística & datos numéricos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , TaiwánRESUMEN
Electrochemical and in situ X-ray absorption spectroscopy (XAS) measurements of various MnO2-coated carbon materials (MnO2/acid-functionalized carbon nanotubes (C-CNT), MnO2/reduced graphene oxide (RGO), and MnO2/RGO-Au electrodes) were conducted to evaluate the supercapacitive performances and electronic structures. MnO2 was deposited on the surface of C-CNT, RGO, and RGO-Au via a spontaneous redox reaction to facilitate the growth of the bulk form of MnO2/C-CNT and the surface forms of MnO2/RGO-based materials. Various forms of MnO2 on the carbon materials exhibited different charge/discharge behaviors. The specific capacitances of the MnO2/RGO and MnO2/RGO-Au electrodes at a current density of 1 A g(-1) were about 433 and 469 F g(-1), respectively; these values are about 1.5 times that of the MnO2/C-CNT (259 F g(-1)) electrode. Specific capacitances of 220 and 281 F g(-1) with retention rates of about 50-60% were obtained from MnO2/RGO and MnO2/RGO-Au, respectively, even at a high current density of 80 A g(-1). Experimental results revealed that the long-term electrochemical stability of the MnO2/RGO-based electrodes (with â¼90% retention) exceeded that of the MnO2/C-CNT electrode (with â¼60% retention) after 1000 cycles at a high scan rate of 80 A g(-1). This finding indicates that MnO2/RGO-based electrodes feature excellent cycling stability and rate capacity retention performance. To elucidate the atomic/electronic structures of the MnO2/C-CNT, MnO2/RGO, and MnO2/RGO-Au electrodes during the charge/discharge process, in situ XAS of the Mn K-edge was performed. The MnO2/RGO-based electrodes exhibited the least variations in the pre-peak intensity of the Mn K-edge during the charge/discharge process because a nano-network of MnO2 is homogeneously decorated on the outer surfaces of RGO-based electrodes to facilitate the growth of surface forms of MnO2/RGO and MnO2/RGO-Au. Analytical results further revealed suppression of changes in tunnel size and promotion of insertion/extraction behavior. This work, particularly the combination of cyclic voltammetry with in situ XAS measurements, will be of general value in the fields of nanomaterials and nanotechnology, and in their use in energy storage.
RESUMEN
The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is involved in the regulation of intestinal stem cell (ISC) activity to ensure a continuous renewal of the adult Drosophila midgut. Three ligands, Unpaired 1, Unpaired 2 and Unpaired 3 (Upd1, Upd2 and Upd3, respectively) are known to activate the JAK/STAT pathway in Drosophila. Using newly generated upd mutants and cell-specific RNAi, we showed that Upd1 is required throughout the fly life to maintain basal turnover of the midgut epithelium by controlling ISC maintenance in an autocrine manner. A role of Upd2 and Upd3 in basal conditions is discernible only in old gut, where they contribute to increased ISC abnormal division. Finally, upon an acute stress such as oral bacterial infection, we showed that Upd3 is released from enterocytes and has an additive effect with Upd2 to promote rapid epithelial regeneration. Taken together, our results show that Upd ligands are required to maintain the midgut homeostasis under both normal and pathological states.
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Drosophila/citología , Intestinos/citología , Células Madre/citología , Animales , Comunicación Autocrina , Diferenciación Celular/fisiología , División Celular , Procesos de Crecimiento Celular/fisiología , Drosophila/genética , Drosophila/metabolismo , Drosophila/microbiología , Proteínas de Drosophila/biosíntesis , Proteínas de Drosophila/genética , Femenino , Mucosa Intestinal/metabolismo , Intestinos/microbiología , Quinasas Janus/metabolismo , Comunicación Paracrina , Pectobacterium carotovorum/fisiología , Factores de Transcripción STAT/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/genéticaRESUMEN
In this study, the successful synthesis of bimetallic nickel/cobalt phosphide nanosheets (Ni-Co-P NSs) via the hydrothermal method and the subsequent high-temperature phosphorization process were both confirmed. Ni-Co-P NSs exhibited excellent electrocatalytic activity for the electrochemical non-enzymatic DA sensing. The surface morphologies and physicochemical properties of Ni-Co-P NSs were characterized by atomic force microscopy (AFM), field-emission scanning (FESEM), field-emission transmission electron microscopy (FETEM), and X-ray diffraction (XRD). Further, the electrochemical performance was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The metallic nature of phosphide and the synergistic effect of Ni/Co atoms in Ni-Co-P NSs provided abundant catalytic active sites for the electrochemical redox reaction of DA, which exhibited a remarkable consequence with a wide linear range from 0.3~50 µM, a high sensitivity of 2.033 µA µM-1 cm-2, a low limit of detection of 0.016 µM, and anti-interference ability. As a result, the proposed Ni-Co-P NSs can be considered an ideal electrode material for the electrochemical non-enzymatic DA sensing.