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1.
Environ Sci Pollut Res Int ; 30(21): 59719-59736, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37014598

RESUMEN

PM2.5 is an important air pollution index, which has been widely concerned. An excellent PM2.5 prediction system can effectively help people protect their respiratory tract from injury. However, due to the strong uncertainty of PM2.5 data, the accuracy of traditional point prediction and interval prediction method is not satisfactory, especially for interval prediction, which is usually difficult to achieve the expected interval coverage (PINC). In order to solve the above problems, a new hybrid PM2.5 prediction system is proposed, which can quantify the certainty and uncertainty of future PM2.5 at the same time. For point prediction, a multi-strategy improved multi-objective crystal algorithm (IMOCRY) is proposed; the chaotic mapping and screening operator are added to make the algorithm more suitable for practical application. At the same time, the combined neural network based on unconstrained weighting method further improves the point prediction accuracy. For interval prediction, a new strategy is proposed, which uses the combination of fuzzy information granulation and variational mode decomposition to process the data. The high-frequency components are extracted by the VMD method, and then quantified by FIG method. By this way, the fuzzy interval prediction results with high coverage and low interval width are obtained. Through 4 groups of experiments and 2 groups of discussions, the advanced nature, accuracy, generalization, and fuzzy prediction ability of the prediction system are all satisfactory, which verified the effect of the system in practical application.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Algoritmos , Material Particulado/análisis
2.
J Clin Immunol ; 42(6): 1280-1292, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35596857

RESUMEN

Ras-related C3 botulinum toxin substrate 2 (RAC2) is a GTPase exclusively expressed in hematopoietic cells that acts as a pivotal regulator of several aspects of cell behavior via various cellular processes. RAC2 undergoes a tightly regulated GTP-binding/GTP-hydrolysis cycle, enabling it to function as a molecular switch. Mutations in RAC2 have been identified in 18 patients with different forms of primary immunodeficiency, ranging from phagocyte defects caused by dominant negative mutations to common variable immunodeficiency resulting from autosomal recessive loss-of-function mutations, or severe combined immunodeficiency due to dominant activating gain-of-function mutations. Here, we describe an 11-year-old girl with combined immunodeficiency presenting with recurrent respiratory infections and bronchiectasis. Immunological investigations revealed low T-cell receptor excision circle/K-deleting recombination excision circles numbers, lymphopenia, and low serum immunoglobulin G. Targeted next-generation sequencing identified a novel heterozygous mutation in RAC2, c.86C > G (p.P29R), located in the highly conserved Switch I domain. The mutation resulted in enhanced reactive oxygen species production, elevated F-actin content, and increased RAC2 protein expression in neutrophils, as well as increased cytokine production and a dysregulated phenotype in T lymphocytes. Furthermore, the dominant activating RAC2 mutation led to accelerated apoptosis with augmented intracellular active caspase 3, impaired actin polarization in lymphocytes and neutrophils, and diminished RAC2 polarization in neutrophils. We present a novel RAC2 gain-of-function mutation with implications for immunodeficiency and linked to functional dysregulation, including abnormal apoptosis and cell polarization arising from altered RAC2 expression. Thus, our findings broaden the spectrum of known RAC2 mutations and their underlying mechanisms.


Asunto(s)
Toxinas Botulínicas , Enfermedades de Inmunodeficiencia Primaria , Actinas/genética , Actinas/metabolismo , Toxinas Botulínicas/genética , Toxinas Botulínicas/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Citocinas/metabolismo , Mutación con Ganancia de Función , Guanosina Trifosfato/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Mutación/genética , Enfermedades de Inmunodeficiencia Primaria/genética , Especies Reactivas de Oxígeno/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Proteínas de Unión al GTP rac/genética , Proteínas de Unión al GTP rac/metabolismo
3.
Front Immunol ; 12: 699743, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34305938

RESUMEN

Background: SCN4 is an autosomal recessive disease caused by mutations in the G6PC3 gene. The clinical, molecular, and immunological features; function of neutrophils; and prognosis of patients with SCN4 have not been fully elucidated. Methods: Two Chinese pediatric patients with G6PC3 mutations were enrolled in this study. Clinical data, genetic and immunologic characteristics, and neutrophil function were evaluated in patients and controls before and after granulocyte colony-stimulating factor (G-CSF) treatment. Results: Both patients had histories of pneumonia, inguinal hernia, cryptorchidism, and recurrent oral ulcers. Patient 1 also had asthma and otitis media, and patient 2 presented with prominent ectatic superficial veins and inflammatory bowel disease. DNA sequencing demonstrated that both patients harbored heterozygous G6PC3 gene mutations. Spontaneous and FAS-induced neutrophil apoptosis were significantly increased in patients, and improved only slightly after G-CSF treatment, while neutrophil respiratory burst and neutrophil extracellular traps production remained impaired in patients after G-CSF treatment. Conclusion: G-CSF treatment is insufficient for patients with SCN4 patients, who remain at risk of infection. Where possible, regular G-CSF treatment, long-term prevention of infection, are the optimal methods for cure of SCN4 patients. It is important to monitor closely for signs of leukemia in SCN4 patients. Once leukemia occurs in SCN4 patients, hematopoietic stem cell transplantation is the most important choice of treatment.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Síndromes Congénitos de Insuficiencia de la Médula Ósea/inmunología , Glucosa-6-Fosfatasa/genética , Neutropenia/congénito , Neutrófilos/inmunología , Pueblo Asiatico/genética , Niño , Humanos , Masculino , Mutación Missense , Neutropenia/genética , Neutropenia/inmunología
4.
Cell Mol Immunol ; 18(7): 1783-1797, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-32099075

RESUMEN

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal-dominant combined immunodeficiency disorder resulting from pathogenic gain-of-function (GOF) mutations in the PIK3CD gene. Patients with APDS display abnormal T cell homeostasis. However, the mechanisms by which PIK3CD GOF contributes to this feature remain unknown. Here, with a cohort of children with PIK3CD GOF mutations from multiple regions of China and a corresponding CRISPR/Cas9 gene-edited mouse model, we reported that hyperactive PI3Kδ disrupted TNaive cell homeostasis in the periphery by intrinsically promoting the growth, proliferation, and activation of TNaive cells. Our results showed that PIK3CD GOF resulted in loss of the quiescence-associated gene expression profile in naive T cells and promoted naive T cells to overgrow, hyperproliferate and acquire an activated functional status. Naive PIK3CD GOF T cells exhibited an enhanced glycolytic capacity and reduced mitochondrial respiration in the resting or activated state. Blocking glycolysis abrogated the abnormal splenic T cell pool and reversed the overactivated phenotype induced by PIK3CD GOF in vivo and in vitro. These results suggest that enhanced aerobic glycolysis is required for PIK3CD GOF-induced overactivation of naive T cells and provide a potential therapeutic approach for targeting glycolysis to treat patients with APDS as well as other immune disorders.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Enfermedades de Inmunodeficiencia Primaria , Animales , Fosfatidilinositol 3-Quinasa Clase I/genética , Glucólisis , Humanos , Ratones , Linfocitos T
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