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INTRODUCTION: Recessive mutations in the CAPN3 gene can lead to limb-girdle muscular dystrophy recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. METHODS: We performed targeted next-generation sequencing of all exons of the CAPN3 gene in 4 patients with sporadic limb-girdle muscular dystrophy (LGMD) and further analyzed the effects of the novel identified variant using various software tools. RESULTS: We found 5 variants in CAPN3 gene in 4 patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. DISCUSSION: Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.
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Pueblo Asiatico , Calpaína , Proteínas Musculares , Distrofia Muscular de Cinturas , Humanos , Calpaína/genética , Distrofia Muscular de Cinturas/genética , Proteínas Musculares/genética , Masculino , Femenino , Pueblo Asiatico/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Adulto , Mutación/genética , China , Adolescente , Exones/genética , Adulto Joven , Pueblos del Este de AsiaRESUMEN
PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.
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Densidad Ósea , Hueso Esponjoso , Húmero , Tomografía Computarizada por Rayos X , Humanos , Densidad Ósea/fisiología , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Reproducibilidad de los Resultados , Húmero/diagnóstico por imagen , Húmero/fisiología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiopatología , Hueso Esponjoso/fisiología , Algoritmos , Fantasmas de Imagen , Adulto , Osteoporosis/fisiopatología , Osteoporosis/diagnóstico por imagen , Anciano de 80 o más AñosRESUMEN
White-light emission with a single activator is an attractive function of phosphors. In this work, we investigated the photoluminescence properties of Ca5.7Y1.3Si7O16.7N3.3, which is a compound denoted as Ca4+xY3-xSi7O15+xN5-x discovered by our group, with Ce-activation using optical measurements and density functional theory (DFT) calculation. Samples showed a tunable emission from purple to white under ultraviolet (UV) light. In this compound, Ca and Y as well as anions are distributed disorderly, and Ca/Y ions occupy two crystallographically distinct sites; those sites are possible sites for Ce substitution. DFT calculation and structural refinement revealed that the tunable emission was generated by Ce at the crystallographically equivalent site but with distinct local structures caused by the disordering of cations and anions. As far as we know, this is the first report about a white-light-emitting phosphor with only Ce activation.
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Up-frameshift protein 1 (UPF1) is essential for nonsense-mediated messenger RNA decay (NMD). It is best known for its cytoprotective role in degrading aberrant and specific RNAs. UPF1 is dysregulated in multiple tumors, which correlates with poor prognosis and low overall survival.However,the role of UPF1 in lung cancer remains unclear.Current study shows that UPF1 could be a potential target for oncology therapies. The results also demonstrated the potential efficiency of UPF1 in regulating the proliferation and metastasis of lung cancer. Our findings suggest that those functions can be attributed to the inhibition of the stability of FOXO1 protein. In addition, PBK participates in the regulation of FOXO1 by UPF1.This result provides a new therapeutic strategy for lung cancer patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Transactivadores/genética , Transactivadores/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Neoplasias Pulmonares/genética , Degradación de ARNm Mediada por Codón sin Sentido , ARN Helicasas/genética , ARN Helicasas/metabolismoRESUMEN
BACKGROUND: Alternative splicing (AS) is a co-transcriptional regulatory mechanism of plants in response to environmental stress. However, the role of AS in biotic and abiotic stress responses remains largely unknown. To speed up our understanding of plant AS patterns under different stress responses, development of informative and comprehensive plant AS databases is highly demanded. DESCRIPTION: In this study, we first collected 3,255 RNA-seq data under biotic and abiotic stresses from two important model plants (Arabidopsis and rice). Then, we conducted AS event detection and gene expression analysis, and established a user-friendly plant AS database termed PlaASDB. By using representative samples from this highly integrated database resource, we compared AS patterns between Arabidopsis and rice under abiotic and biotic stresses, and further investigated the corresponding difference between AS and gene expression. Specifically, we found that differentially spliced genes (DSGs) and differentially expressed genes (DEG) share very limited overlapping under all kinds of stresses, suggesting that gene expression regulation and AS seemed to play independent roles in response to stresses. Compared with gene expression, Arabidopsis and rice were more inclined to have conserved AS patterns under stress conditions. CONCLUSION: PlaASDB is a comprehensive plant-specific AS database that mainly integrates the AS and gene expression data of Arabidopsis and rice in stress response. Through large-scale comparative analyses, the global landscape of AS events in Arabidopsis and rice was observed. We believe that PlaASDB could help researchers understand the regulatory mechanisms of AS in plants under stresses more conveniently. PlaASDB is freely accessible at http://zzdlab.com/PlaASDB/ASDB/index.html .
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Arabidopsis , Oryza , Empalme Alternativo , Arabidopsis/metabolismo , Plantas/genética , Perfilación de la Expresión Génica , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Oryza/metabolismo , Proteínas de Plantas/genéticaRESUMEN
Bioinformatics analysis of a whole genome sequence coupled with HPLC-DAD analysis revealed that Streptomyces sp. Hu103 has the capacity to produce skyllamycin analogues. A subsequent chemical investigation of this strain yielded four new cinnamoyl-containing cyclopeptides, anulamycins A-D (1-4), two new cinnamoyl-containing linear peptides, anulamycins E and F (5 and 6), and two known cyclopeptides, skyllamycins A (7) and B (8). Their structures including absolute configurations were elucidated by detailed analysis of NMR and HRESIMS/MS spectroscopic data and the advanced Marfey's method. Compounds 1-4 exhibited antibacterial activity comparable to those of skyllamycins A and B.
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Streptomyces , Streptomyces/química , Lagos , Péptidos Cíclicos/química , Espectroscopía de Resonancia Magnética , Antibacterianos/química , Estructura MolecularRESUMEN
Antibodies play essential roles in both diagnostics and therapeutics. Epitope mapping is essential to understand how an antibody works and to protect intellectual property. Given the millions of antibodies for which epitope information is lacking, there is a need for high-throughput epitope mapping. To address this, we developed a strategy, Antibody binding epitope Mapping (AbMap), by combining a phage displayed peptide library with next-generation sequencing. Using AbMap, profiles of the peptides bound by 202 antibodies were determined in a single test, and linear epitopes were identified for >50% of the antibodies. Using spike protein (S1 and S2)-enriched antibodies from the convalescent serum of one COVID-19 patient as the input, both linear and potentially conformational epitopes of spike protein specific antibodies were identified. We defined peptide-binding profile of an antibody as the binding capacity (BiC). Conceptually, the BiC could serve as a systematic and functional descriptor of any antibody. Requiring at least one order of magnitude less time and money to map linear epitopes than traditional technologies, AbMap allows for high-throughput epitope mapping and creates many possibilities.
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COVID-19/inmunología , Mapeo Epitopo/métodos , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Epítopos/metabolismo , Proteínas de Escherichia coli/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Sueros Inmunes/sangre , Sueros Inmunes/inmunología , Biblioteca de PéptidosRESUMEN
Breast cancer is the most common malignancy diagnosed in women worldwide. The prevalence and incidence of breast cancer is increasing every year; therefore, early diagnosis along with suitable relapse detection is an important strategy for prognosis improvement. This study aimed to compare different machine algorithms to select the best model for predicting breast cancer recurrence. The prediction model was developed by using eleven different machine learning (ML) algorithms, including logistic regression (LR), random forest (RF), support vector classification (SVC), extreme gradient boosting (XGBoost), gradient boosting decision tree (GBDT), decision tree, multilayer perceptron (MLP), linear discriminant analysis (LDA), adaptive boosting (AdaBoost), Gaussian naive Bayes (GaussianNB), and light gradient boosting machine (LightGBM), to predict breast cancer recurrence. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score were used to evaluate the performance of the prognostic model. Based on performance, the optimal ML was selected, and feature importance was ranked by Shapley Additive Explanation (SHAP) values. Compared to the other 10 algorithms, the results showed that the AdaBoost algorithm had the best prediction performance for successfully predicting breast cancer recurrence and was adopted in the establishment of the prediction model. Moreover, CA125, CEA, Fbg, and tumor diameter were found to be the most important features in our dataset to predict breast cancer recurrence. More importantly, our study is the first to use the SHAP method to improve the interpretability of clinicians to predict the recurrence model of breast cancer based on the AdaBoost algorithm. The AdaBoost algorithm offers a clinical decision support model and successfully identifies the recurrence of breast cancer.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Teorema de Bayes , Mama , Algoritmos , Aprendizaje AutomáticoRESUMEN
Two previously undescribed pyrrolizine alkaloids, named phenopyrrolizins A and B (1 and 2), were obtained from the fermentation broth of marine-derived Micromonospora sp. HU138. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR spectra as well as HRESIMS data. The structure of 1 was confirmed by single-crystal diffraction analysis and its racemization mechanism was proposed. The antifungal activity assay showed that 2 could inhibit the mycelial growth of Botrytis cinerea with the inhibitory rates of 18.9% and 35.9% at 20 µg/disc and 40 µg/disc, respectively.
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Actinobacteria , Alcaloides , Micromonospora , Actinomyces , Micromonospora/química , Alcaloides/farmacología , Alcaloides/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade â ¢ or â £, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS: There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
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Cardiomiopatía Dilatada , Función Ventricular Izquierda , Masculino , Femenino , Humanos , Niño , Volumen Sistólico , Estudios Retrospectivos , Fenotipo , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/diagnóstico , Mutación , ATPasas Asociadas con Actividades Celulares Diversas/genética , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genéticaRESUMEN
A chemical investigation of Streptomyces sp. Hu186 afforded two known quinone antibiotics, sarubicin A (1) and sarubicin B (2), together with three unusual variants, sarubicinols A-C (3-5), and two new 1,4-naphthoquinone metabolites, sarubicin B1 (6) and sarubicin B2 (7). Compounds 3-5 possess a rare 2-oxabicyclo [2.2.2] substructure and a benzoxazole ring system. Their structures were elucidated using 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The absolute configurations of the side-chain moieties in 4 and 5 were solved by electronic circular dichroism calculations. Compounds 1-7 showed moderate cytotoxic activity against four tumor cell lines.
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Antineoplásicos , Streptomyces , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Benzoxazoles/farmacología , Línea Celular Tumoral , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray , Streptomyces/químicaRESUMEN
Age has been found to be one of the main risk factors for the severity and outcome of COVID-19. However, differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown. In this study, we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups. By antibody response landscape maps, we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age. The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence, disease severity and age of the COVID-19 patients. Furthermore, the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged <50 and high S1 IgG responses are enriched in mild COVID-19 patients aged >60. In addition, high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged >70. These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age, which may facilitate a deeper understanding of the immune responses in COVID-19 patients.
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Factores de Edad , Formación de Anticuerpos , COVID-19 , Anciano , Anticuerpos Antivirales/sangre , COVID-19/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Persona de Mediana Edad , Péptidos , SARS-CoV-2 , Glicoproteína de la Espiga del CoronavirusRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the ability of a novel artificial intelligence (AI) model in identifying optimized transpedicular screw trajectories with higher bone mineral density (BMD) as well as higher pull-out force (POF) in osteoporotic patients. METHODS: An innovative pedicle screw trajectory planning system called Bone's Trajectory was developed using a 3D graphic search and an AI-based finite element analysis model. The preoperative CT scans of 21 elderly osteoporotic patients were analyzed retrospectively. The AI model automatically calculated the number of alternative transpedicular trajectories, the trajectory BMD, and the estimated POF of L3-5. The highest BMD and highest POF of optimized trajectories were recorded and compared with AO standard trajectories. RESULTS: The average patient age and average BMD of the vertebral bodies were 69.6 ± 7.8 years and 55.9 ± 17.1 mg/ml, respectively. On both sides of L3-5, the optimized trajectories showed significantly higher BMD and POF than the AO standard trajectories (p < 0.05). On average, the POF of optimized trajectory screws showed at least a 2.0-fold increase compared with AO trajectory screws. CONCLUSIONS: The novel AI model performs well in enabling the selection of optimized transpedicular trajectories with higher BMD and POF than the AO standard trajectories.
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Tornillos Pediculares , Fusión Vertebral , Anciano , Inteligencia Artificial , Densidad Ósea , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients. METHODS: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias. RESULTS: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, I2 = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, I2 = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, I2 = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant. CONCLUSIONS: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.
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Disfunción Cognitiva , Enfermedad de Parkinson , Cognición , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Magnética Transcraneal , Resultado del TratamientoRESUMEN
Two previously undescribed cyclopentenone metabolites, (S)-2-(3-acetylamino-2-methyl)propyl-3-butyl-2-cyclopenten-1-one (1) and (S)-2-(3-acetylamino-2-ethyl)propyl-3-butyl-2-cyclopenten-1-one (2), were isolated from the fermentation broth of the strain Streptomyces sp. HU119. The structures of 1 and 2 were determined by the comprehensive spectroscopic analysis, including 1 D, 2 D NMR, MS spectral analysis and the comparison with data from the literature. The absolute configurations were elucidated by experimental and calculated optical rotations (OR). Compounds 1 and 2 displayed weak cytotoxic activity.
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Streptomyces , Streptomyces/química , Estructura Molecular , Ciclopentanos/farmacología , FermentaciónRESUMEN
Alternative splicing (AS) is an essential co-transcriptional regulatory mechanism in eukaryotes. The accumulation of plant RNA-Seq data provides an unprecedented opportunity to investigate the global landscape of plant AS events. However, most existing AS identification tools were originally designed for animals, and their performance in plants was not rigorously benchmarked. In this work, we developed a simple and easy-to-use bioinformatics tool named ASTool for detecting AS events from plant RNA-Seq data. As an exon-based method, ASTool can detect 4 major AS types, including intron retention (IR), exon skipping (ES), alternative 5' splice sites (A5SS), and alternative 3' splice sites (A3SS). Compared with existing tools, ASTool revealed a favorable performance when tested in simulated RNA-Seq data, with both recall and precision values exceeding 95% in most cases. Moreover, ASTool also showed a competitive computational speed and consistent detection results with existing tools when tested in simulated or real plant RNA-Seq data. Considering that IR is the most predominant AS type in plants, ASTool allowed the detection and visualization of novel IR events based on known splice sites. To fully present the functionality of ASTool, we also provided an application example of ASTool in processing real RNA-Seq data of Arabidopsis in response to heat stress.
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Empalme Alternativo , Arabidopsis , Animales , Arabidopsis/genética , Biología Computacional/métodos , Sitios de Empalme de ARN , ARN de Planta/genética , RNA-Seq , Análisis de Secuencia de ARN/métodosRESUMEN
Poly(cyclopentene carbonate) (PCPC) produced by copolymerization of CO2 and cyclopentene oxide (CPO) is a promising but challenging chemical recyclable polymer that has high potential in minimizing plastic pollution and maximizing CO2 utilization. Currently, problems remain to be solved, include low reactivity of toxic metal catalysts, inevitable byproducts, and especially the ambiguous mechanism understanding. Herein, we present the first metal-free access to PCPC by using a series of modular dinuclear organoboron catalysts. PCPC was afforded in an unprecedented catalytic efficiency of 1.0â kg of PCPC/g of catalyst; while the depolymerization of PCPC abides by a combination pathway of random chain scission and chain unzipping, returning CPO in near-quantitative yield (>99 %). The preparation and depolymerization of PCPC along with in depth understanding of related mechanisms would be helpful for further development of advanced catalysts and recyclable plastics.
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It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In the current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H2 O2 ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H2 O2 in LUAD cells and that the AQP3-dependent transport of H2 O2 accelerated cell growth and inhibited rapamycin-induced autophagy. Mechanistically, AQP3-mediated H2 O2 uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway to subsequently inhibit autophagy and promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.
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Adenocarcinoma del Pulmón/patología , Acuaporina 3/genética , Acuaporina 3/metabolismo , Peróxido de Hidrógeno/metabolismo , Neoplasias Pulmonares/patología , Fosfohidrolasa PTEN/metabolismo , Células A549 , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Animales , Autofagia , Línea Celular Tumoral , Proliferación Celular , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Trasplante de Neoplasias , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Sirolimus/farmacologíaRESUMEN
BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Portador Sano/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/diagnóstico , Prueba de COVID-19/métodos , Portador Sano/sangre , Portador Sano/diagnóstico , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana EdadRESUMEN
A simple colorimetric sensing strategy for Hg2+ ions was developed using silver/copper nanoclusters (Ag/Cu NCs) with excellent selectivity and sensitivity. Bimetallic Ag/Cu NCs were synthesized by using glutathione (GSH) as a template and sodium borohydride as a reducing agent. It was found that the peroxidase-like activity of Ag/Cu NCs was significantly enhanced in the presence of Hg2+. Therefore, a colorimetric method based on catalysis was developed to detect Hg2+ with a linear concentration range of 0.1-700 nM and a detection limit of 0.05 nM (S/N = 3). The common species have no effect on Hg2+ ion detection. Furthermore, this method is applicable to accurately detect Hg2+ in real aqueous samples and is reproducible. Therefore, owing to the merits of sensitivity, selectivity, rapid response and visual read-out, it can be promising in the development of a portable Hg2+ analyzer for on-site detection.