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Here, Molecular Cell talks to first and co-corresponding author Lizhen Chen and co-corresponding authors Shasha Chong and Zhijie "Jason" Liu about their paper, ''Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions'' (in this issue of Molecular Cell) and their scientific journeys until now.
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Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates through multivalent interactions mediated by its N-terminal intrinsically disordered region (IDR) to orchestrate enhancer assembly in response to androgen signaling. AR IDR can be substituted by IDRs from selective proteins for AR condensation capacity and its function on enhancers. Expansion of the poly(Q) track within AR IDR results in a higher AR condensation propensity as measured by multiple methods, including live-cell single-molecule microscopy. Either weakening or strengthening AR condensation propensity impairs its heterotypic multivalent interactions with other enhancer components and diminishes its transcriptional activity. Our work reveals the requirement of an optimal level of AR condensation in mediating enhancer assembly and suggests that alteration of the fine-tuned multivalent IDR-IDR interactions might underlie AR-related human pathologies.
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Elementos de Facilitación Genéticos , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hormonas , Transducción de SeñalRESUMEN
YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2/ERα target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ERα cofactors in regulating cancer growth, highlighting the potential of YAP/TEAD as possible actionable drug targets for ERα+ breast cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/metabolismo , Proteínas de Unión al ADN/metabolismo , Elementos de Facilitación Genéticos , Estrógenos/farmacología , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas de Unión al ADN/genética , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Células MCF-7 , Subunidad 1 del Complejo Mediador/genética , Subunidad 1 del Complejo Mediador/metabolismo , Ratones , Ratones Desnudos , Proteínas Musculares/genética , Proteínas de Neoplasias/genética , Factores de Transcripción de Dominio TEA , Factores de Transcripción/genética , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.
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Resección Endoscópica de la Mucosa , Inhibidores de la Bomba de Protones , Pirroles , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Gástrica , Sulfonamidas , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Sulfonamidas/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Pirroles/uso terapéutico , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres. METHODS: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups. RESULTS: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects. CONCLUSION: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Lactante , Humanos , Recién Nacido , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Tamizaje Neonatal , Estudios de Seguimiento , Terapia de Reemplazo Enzimático , EcocardiografíaRESUMEN
BACKGROUND: Adelphocoris suturalis (Hemiptera: Miridae) is a notorious agricultural pest, which causes serious economic losses to a diverse range of agricultural crops around the world. The poor understanding of its genomic characteristics has seriously hindered the establishment of sustainable and environment-friendly agricultural pest management through biotechnology and biological insecticides. RESULTS: Here, we report a chromosome-level assembled genome of A. suturalis by integrating Illumina short reads, PacBio, 10x Chromium, and Hi-C mapping technologies. The resulting 1.29 Gb assembly contains twelve chromosomal pseudomolecules with an N50 of 1.4 and 120.6 Mb for the contigs and scaffolds, respectively, and carries 20,010 protein-coding genes. The considerable size of the A. suturalis genome is predominantly attributed to a high amount of retrotransposons, especially long interspersed nuclear elements (LINEs). Transcriptomic and phylogenetic analyses suggest that A. suturalis-specific candidate effectors, and expansion and expression of gene families associated with omnivory, insecticide resistance and reproductive characteristics, such as digestion, detoxification, chemosensory receptors and long-distance migration likely contribute to its strong environmental adaptability and ability to damage crops. Additionally, 19 highly credible effector candidates were identified and transiently overexpressed in Nicotiana benthamiana for functional assays and potential targeting for insect resistance genetic engineering. CONCLUSIONS: The high-quality genome of A. suturalis provides an important genomic landscape for further investigations into the mechanisms of omnivory, insecticide resistance and survival adaptation, and for the development of integrated management strategies.
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Genómica , Resistencia a los Insecticidas , Resistencia a los Insecticidas/genética , Filogenia , Agricultura , Productos Agrícolas , CromosomasRESUMEN
To explore the impact of shade treatment on grape berries, 'Marselan' grape berries were bagged under different light transmission rates (100% (CK), 75% (A), 50% (B), 25% (C), 0% (D)). It was observed that this treatment delayed the ripening of the grape berries. The individual weight of the grape berries, as well as the content of fructose, glucose, soluble sugars, and organic acids in the berries, was measured at 90, 100, and 125 days after flowering (DAF90, DAF100, DAF125). The results revealed that shading treatment reduced the sugar content in grape berries; the levels of fructose and glucose were higher in the CK treatment compared to the other treatments, and they increased with the duration of the shading treatment. Conversely, the sucrose content exhibited the opposite trend. Additionally, as the weight of the grape berries increased, the content of soluble solids and soluble sugars in the berries also increased, while the titratable acidity decreased. Furthermore, 16 differentially expressed genes (DEGs) were identified in the photosynthesis-antenna protein pathway from the transcriptome sequencing data. Correlation analysis revealed that the expression levels of genes VIT_08s0007g02190 (Lhcb4) and VIT_15s0024g00040 (Lhca3) were positively correlated with sugar content in the berries at DAF100, but negatively correlated at DAF125. qRT-PCR results confirmed the correlation analysis. This indicates that shading grape clusters inhibits the expression of genes in the photosynthesis-antenna protein pathway in the grape berries, leading to a decrease in sugar content. This finding contributes to a deeper understanding of the impact mechanisms of grape cluster shading on berry quality, providing important scientific grounds for improving grape berry quality.
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Frutas , Regulación de la Expresión Génica de las Plantas , Fotosíntesis , Proteínas de Plantas , Azúcares , Vitis , Vitis/genética , Vitis/metabolismo , Vitis/efectos de la radiación , Frutas/genética , Frutas/metabolismo , Frutas/efectos de la radiación , Fotosíntesis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Azúcares/metabolismo , LuzRESUMEN
The development of electrochemical DNA biosensors has been limited by their reliability and reproducibility due to many interfering factors such as electrode properties, DNA surface densities, and complex biological samples. In this work, we developed a nanobalance polyA hairpin probe (polyA-HP), which was effectively assembled onto the gold electrode surface through the affinity between the central polyA fragment and the Au surface. One flanking probe of the polyA-HP captured the target sequence together with a MB-labeled signal probe, and the other flanking probe captured a reference probe simultaneously. The MB signal related to the amount of target was normalized by the reference Fc signal; thus, the signal-to-noise (S/N) was as high as 2000, and the reproducibility was remarkably improved to 2.77%, even facing deliberately changed experiment conditions. By designing a hairpin structure at the terminal of the polyA-HP, the selectivity and specificity were dramatically improved for the analysis of mismatched sequences. The analysis performance of biological samples was dramatically improved after normalization, which is critical for its practicability. Our novel biosensor is a universal single-molecule platform for ratiometric biosensors with excellent performance in real samples, indicating great potential for next-generation high-precision electrochemical sensors.
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Técnicas Biosensibles , Técnicas Electroquímicas , Reproducibilidad de los Resultados , ADN/análisis , Oro/química , Límite de DetecciónRESUMEN
Carbon dots (CDs), a new type of carbon-based fluorescent nanomaterial, have attracted widespread attention because of their numerous excellent properties. Lignocellulosic biomass is the most abundant renewable natural resource and possesses broad potential to manufacture different composite and smart materials. Numerous studies have explored the potential of using the components (such as cellulose, hemicellulose, and lignin) in lignocellulosic biomass to produce CDs. There are few papers systemically aiming in the review of the state-of-the-art works related to lignocellulosic biomass-derived CDs. In this review, the significant advances in synthesis processes, formation mechanisms, structural characteristics, optical properties, and applications of lignocellulosic biomass-based CDs such as cellulose-based CDs, hemicellulose-based CDs and lignin-based CDs in latest research are reviewed. In addition, future research directions on the improvement of the synthesis technology of CDs using lignocellulosic biomass as raw materials to enhance the properties of CDs are proposed. This review will serve as a road map for scientists engaged in research and exploring more applications of CDs in different science fields to achieve the highest material performance goals of CDs.
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Adhesive gels derived from biobased sustainable materials have extremely broad application prospects, such as in flexible smart materials and biomedicine fields. Combining high toughness and strong, persisting repeatable adhesion has always been a daunting challenge for adhesive gels. However, bulk gels based on polysaccharides as the most abundant bio-based compounds usually possess a high toughness but weak interfacial adhesion due to the strong hydration potential. Herein, a novel kind of highly tough microgel membranes with rough surfaces is fabricated using loosely chemically cross-linked dihydroxypropyl cellulose (cDHPC) microgels (average size = 1.25 ± 0.03 µm). Such microgel membranes exhibit strong, instant, and persisting adhesion to various substrates with different surface roughness. Slight chemical cross-linking and multiple physical interactions within microgels and resulting microgel membranes lead to high tensile strength and toughness of 0.23 ± 0.03 MPa and 73.8 ± 9.3 KJ m-3 , respectively. The maximum adhesive strength and debonding work exceed 320 ± 0.50 KPa and 160.97 ± 0.20 J m-2 , respectively. After five cycles (re-lap after detaching), the adhesive strength still remains above 200 KPa. Their adhesive properties outperform most bio-based adhesive gels and even petroleum-based gels, which are based on synergistic molecular and microscaled topological interactions.
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Nanozymes are nanomaterials with biocatalytic properties under physiological conditions and are one class of artificial enzymes to overcome the high cost and low stability of natural enzymes. However, surface ligands on nanomaterials will decrease the catalytic activity of the nanozymes by blocking the active sites. To address this limitation, ligand-free PtAg nanoclusters (NCs) are synthesized and applied as nanozymes for various enzyme-mimicking reactions. By taking advantage of the mutual interaction of zeolitic imidazolate frameworks (ZIF-8) and Pt precursors, a good dispersion of PtAg bimetal NCs with a diameter of 1.78 ± 0.1 nm is achieved with ZIF-8 as a template. The incorporation of PtAgNCs in the voids of ZIF-8 is confirmed with structural analysis using the atomic pair-distribution function and powder X-ray diffraction. Importantly, the PtAgNCs present good catalytic activity for various enzyme-mimicking reactions, including peroxidase-/catalase- and oxidase-like reactions. Further, this work compares the catalytic activity between PtAg NCs and PtAg nanoparticles with different compositions and finds that these two nanozymes present a converse dependency of Ag-loading on their activity. This study contributes to the field of nanozymes and presents a potential option to prepare ligand-free bimetal biocatalysts with sizes in the nanocluster regime.
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Nanopartículas del Metal , Imitación Molecular , Peroxidasa/química , Peroxidasa/metabolismo , Nanopartículas del Metal/química , Platino (Metal)/química , Plata/química , Aleaciones/químicaRESUMEN
A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (â¼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.
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Técnicas Biosensibles , Diabetes Gestacional , Óxido de Aluminio , Aminas , Diabetes Gestacional/diagnóstico , Enzimas Inmovilizadas/metabolismo , Femenino , Glucosa , Glucosa Oxidasa/metabolismo , Humanos , Embarazo , Dióxido de SilicioRESUMEN
The peptide hormone insulin has essential roles in regulating insect metabolism, growth, and reproduction. There are, however, few studies assessing the effects of insulin signaling on reproduction in Miridae (Hemiptera). Here, we used RNA interference (RNAi)-mediated knockdown to examine the role of three critical insulin signaling pathway components (insulin receptor, InR; insulin receptor substrate 1, IRS1; and forkhead box O, FOXO) on reproductive capacity in the mirid Adelphocoris suturalis. Knockdown of AsIRS1 led to a significant reduction in egg maturation in unmated females. To further verify the role of AsIRS1, we examined several reproductive parameters following knockdown. Suppression of AsIRS1 transcript levels throughout the reproductive period resulted in reduced lifetime fecundity, egg hatch rate, and oviposition capacity as well as statistically significant reductions in female survival rate and longevity. These findings demonstrate that the insulin signaling pathway plays a key role in the reproductive development of A. suturalis, and that IRS1 is a key regulatory factor. These findings provide an important theoretical basis for the regulation of insect reproduction by insulin and introduce a new target for potential development is A. suturalis control.
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Heterópteros , Receptor de Insulina , Animales , Femenino , Insulina , Proteínas Sustrato del Receptor de Insulina/genética , Receptor de Insulina/genética , Reproducción , Transducción de SeñalRESUMEN
Plant bugs (Miridae species) have become major agricultural pests that cause increasing and severe economic damage. Plant-mediated RNA interference (RNAi) is emerging as an eco-friendly, efficient, and reliable strategy for pest management. In this study, we isolated and characterized a lethal gene of Apolygus lucorum and named it Apolygus lucorum LIM (AlLIM), which produced A. lucorum mortality rates ranging from 38% to 81%. Downregulation of the AlLIM gene expression in A. lucorum by injection of a double-stranded RNA (dsRNA) led to muscle structural disorganization that resulted in metamorphosis deficiency and increased mortality. Then we constructed a plant expression vector that enabled transgenic cotton to highly and stably express dsRNA of AlLIM (dsAlLIM) by Agrobacterium-mediated genetic transformation. In the field bioassay, dsAlLIM transgenic cotton was protected from A. lucorum damage with high efficiency, with almost no detectable yield loss. Therefore, our study successfully provides a promising genetically modified strategy to overpower A. lucorum attack.
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Gossypium/parasitología , Heterópteros/genética , Insectos/genética , Interferencia de ARN/inmunología , Animales , Plantas/parasitologíaRESUMEN
The development of electrochemiluminescence (ECL) emitters remains a great research interest in ECL analysis. Herein, luminol-doped polymer dots (L-Pdots) and diethylamine-coupled Pdots (N-Pdots) were synthesized to design a both potential- and color-resolved ECL strategy. L-Pdots showed the maximum ECL emission at 450 nm in the presence of hydrogen peroxide at +0.6 V, while the maximum emission of N-Pdots was at 675 nm under +1.0 V. This strategy was conveniently used to construct a novel ECL array imaging method for high-throughput detection of two microRNAs (miRNAs). The array was prepared with the mixture of L-Pdots and N-Pdots that were covalently modified with quencher-labeled DNAs, respectively, to recognize the corresponding miRNAs. Upon the addition of duplex-specific nuclease, the DNAs hybridized with miRNAs were digested to release the quenchers and miRNAs, which led to the ECL recovery of Pdots and target-cyclic signal amplification. By imaging the array at +0.6 and +1.0 V and using miRNA-21 and miRNA-205 as the analytes, the blue and red channel images could be extracted to quantify these miRNAs with detection limits of 2.5 and 3.1 pM, respectively. This work provides a new family member of potential- or color-resolved ECL emitters and successfully realizes the simultaneous and high-throughput sensing of multiplex miRNAs.
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Técnicas Biosensibles , MicroARNs , Puntos Cuánticos , Técnicas Electroquímicas , Mediciones Luminiscentes , PolímerosRESUMEN
Depressive symptoms are common in patients with first-episode psychosis. However, the neural mechanisms underlying the comorbid depression in schizophrenia are still unknown. The main purpose of this study was to characterize the structural abnormalities of first-episodes drug-naïve (FEDN) schizophrenia comorbid with depression by utilizing both volume-based and surface-based morphometric measurements. Forty-two patients with FEDN schizophrenia and 29 healthy controls were recruited. The 24-item Hamilton Depression Rating Scale (HAMD-24) was administrated to divide all patients into depressive patients (DP) and non-depressive patients (NDP). Compared with NDP, DP had a significantly larger volume and surface area in the left isthmus cingulate cortex and also had a greater volume in the left posterior cingulate cortex. Correlation analysis showed that HAMD total score was positively correlated with the surface area of the left isthmus cingulate and gray matter volume of the left isthmus cingulate cortex. In addition, gray matter volume of the left isthmus cingulate was also correlated with the PANSS general psychopathology or total score. The findings suggest that prominent structural abnormalities of gray matter are mainly concentrated on the cingulate cortex in FEDN schizophrenia patients comorbid with depression, which may contribute to depressive symptoms and psychopathological symptoms.
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Depresión/patología , Trastorno Depresivo/patología , Giro del Cíngulo/patología , Esquizofrenia/patología , Adolescente , Adulto , Comorbilidad , Depresión/diagnóstico por imagen , Depresión/epidemiología , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/epidemiología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/epidemiología , Adulto JovenRESUMEN
Millions of people were infected with the coronavirus disease 2019 (COVID-19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID-19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS-CoV-2 infection which were published from 1st January to 21st April 2020. Studies with more than five pediatric inpatients were included in our meta-analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS-CoV-2 infection and the other clinical characters, such as diarrhea, vomiting, nasal congestion, and fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95% confidence interval [CI]: 0.27-0.59) and severe cases was 0.03 (95% CI: 0.01-0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase (19%), lymphopenia (16%), high alanine aminotransferase (15%), high C-reactive protein (17%), leukocytosis (13%), high D-dimer (12%) and high creatine kinase-MB (5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS-CoV-2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS-CoV-2 infection in other countries should be conducted.
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COVID-19/diagnóstico , COVID-19/fisiopatología , COVID-19/sangre , Niño , Tos/virología , Fiebre/virología , Humanos , Pacientes Internos , Estudios Observacionales como Asunto , Tórax/diagnóstico por imagen , Tórax/virología , Tomografía Computarizada por Rayos XRESUMEN
Circular RNAs (circRNAs) may serve as potential biomarkers for patients with lung cancer. The aim of this meta-analysis was to analyse the diagnostic, prognostic and clinicopathological values of circRNAs in lung cancer patients. A systematic search of PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases was performed for relevant articles from inception to 29 January 2020. Pooled parameters including sensitivity, specificity and area under the curve (AUC) were used to assess the diagnostic performance, HRs and 95% CIs were used to evaluate overall survival (OS) and ORs were used to estimate clinicopathological parameters. 52 studies from 45 articles were enrolled in this study, including 17 on diagnosis and 35 on prognosis. For diagnostic values, circRNAs could discriminate lung cancer patients from the controls, with AUC of 0.83 (95% CI: 0.79 to 0.86), a relatively high sensitivity of 0.77 (95% CI: 0.73 to 0.81) and speciï¬city of 0.75 (95% CI: 0.71 to 0.79). For prognostic significances, overexpression of 23 upregulated circRNAs was relevant to a poor prognosis (OS: HR=2.21, 95% CI: 1.96 to 2.49, p<0.001), and overexpression of 9 downregulated circRNAs was correlated with a favourable prognosis (OS: HR=0.62, 95% CI: 0.53 to 0.73, p<0.001). As for clinicopathological parameters, high expression of 23 upregulated circRNAs was associated with unfavourable clinicopathological features while 9 downregulated circRNAs proved the contrary. In conclusion, this study confirmed that circRNAs might serve as important biomarkers for diagnostic and prognostic values of lung cancer.
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Técnicas Genéticas , Neoplasias Pulmonares , ARN Circular , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Valor Predictivo de las Pruebas , Pronóstico , ARN Circular/análisis , ARN Circular/genética , Análisis de SupervivenciaRESUMEN
A competitive strategy for glycan determination on cell surface with organic electrochemical transistors (OECTs) has been developed. The carboxylic multi-wall carbon nanotubes were firstly immobilized on the gate interface to cross-link the specific monose with adipic dihydrazide as the linker, which could then competitively recognize horseradish peroxidase (HRP)-labeled lectin with the target monose on the cell surface. The HRP captured on the gate interface through the affinity of lectin to monose finally catalyzed the reduction of hydrogen peroxide to produce the output current signal for detection of cell surface monose under the optimal gate voltage of 0.9 V. Using mannose and galactose groups as the target models, HRP-labeled concanavalin A and peanut agglutinin were used to competitively recognize these groups on both cell surface and gate interface, respectively. The amounts of mannose and galactose on HeLa cells were measured to be 3.41 × 108 and 2.92 × 108 molecules per cell, respectively. The changes of the mannose and galactose expressions upon external stimulation were also observed with the proposed biosensors, which showed consistent results with flow cytometric analysis, indicating that the OECT-based biosensor is suitable for analysis of different glycan expressions on cell surface. Graphical abstract.
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Membrana Celular/química , Peroxidasa de Rábano Silvestre/química , Lectinas/química , Nanotubos de Carbono/química , Polisacáridos/análisis , Técnicas Biosensibles , Concanavalina A/química , Técnicas Electroquímicas , Galactosa/análisis , Células HeLa , Humanos , Peróxido de Hidrógeno/química , Manosa/análisis , Oxidación-Reducción , Polisacáridos/genéticaRESUMEN
The controllable growth of metal nanoparticles on nanomaterials is becoming a useful strategy for developing nanocomposites with designated performance. Here, a DNA-controlled strategy for growth of Pt nanoparticles on graphene oxide (GO-PtNPs) to regulate the nanozyme activity and a triplex-hybridization chain reaction (tHCR) for triggering the assembly of DNA probes to amplify the target-induced nanozyme catalytic signal were designed. The tHCR with one linear and two hairpin probes could be specially triggered by a tHCR trigger to form a long double-stranded DNA structure in the presence of target nucleic acid, which hindered the adsorption of these probes on a GO surface, and thus accelerated the growth of PtNPs. The formed GO-PtNPs showed strong catalytic activity toward the oxidation of 3,3,5,5-tetramethylbenzidine, thereby producing an amplified "turn-on" detection signal. The proposed method showed very high sensitivity with the detection limits down to 14.6 pM for mutant KRAS DNA and 21.7 pM for let-7a microRNA. This method was validated with better analytical performance than a general HCR system and could be effectively used for the identification of single-nucleotide polymorphisms, thus providing a novel approach for simple and sensitive detection of nucleic acids.