Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 339
Filtrar
Más filtros

País/Región como asunto
Intervalo de año de publicación
1.
Sci Rep ; 14(1): 21101, 2024 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256540

RESUMEN

This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Humanos , Femenino , Masculino , Enfermedades Pulmonares Intersticiales/diagnóstico , Proyectos Piloto , Anciano , Persona de Mediana Edad , Frecuencia Cardíaca , Saturación de Oxígeno , Monitoreo Fisiológico/métodos , Progresión de la Enfermedad
2.
Poult Sci ; 103(12): 104296, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39305615

RESUMEN

The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.

3.
World J Clin Cases ; 12(26): 5922-5929, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39286384

RESUMEN

BACKGROUND: Real-time shear wave elastography (SWE) is a non-invasive imaging technique used to measure tissue stiffness by generating and tracking shear waves in real time. This advanced ultrasound-based method provides quantitative information regarding tissue elasticity, offering valuable insights into the mechanical properties of biological tissues. However, the application of real-time SWE in the musculoskeletal system and sports medicine has not been extensively studied. AIM: To explore the practical value of real-time SWE for assessing Achilles tendon hardness in older adults. METHODS: A total of 60 participants were enrolled in the present study, and differences in the elastic moduli of the bilateral Achilles tendons were compared among the following categories: (1) Age: 55-60, 60-65, and 65-70-years-old; (2) Sex: Male and female; (3) Laterality: Left and right sides; (4) Tendon state: Relaxed and tense state; and (5) Tendon segment: Proximal, middle, and distal. RESULTS: There were no significant differences in the elastic moduli of the bilateral Achilles tendons when comparing by age or sex (P > 0.05). There were, however, significant differences when comparing by tendon side, state, or segment (P < 0.05). CONCLUSION: Real-time SWE plays a significant role compared to other examination methods in the evaluation of Achilles tendon hardness in older adults.

4.
J Org Chem ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298438

RESUMEN

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1H)-ones to produce phosphorylated dihydroquinoxalin-2(1H)-ones has been reported. A wide variety of phosphorylated products were formed in good to excellent yields. Preliminary mechanistic studies reveal that the phosphorylation process involves an EnT process, a SET process, a HAT process, and a deprotonation process.

5.
Cell Signal ; 124: 111378, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39241901

RESUMEN

Crosstalk between cancer-associated fibroblasts (CAFs) and tumour cells plays a critical role in multiple cancers, including hepatocellular carcinoma (HCC). CAFs contribute to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. However, effect and mechanism of CAF-mediated promotion of hepatocellular carcinoma cells are still unclear. In study, we demonstrated CAFs promoted the proliferation and inhibited the apoptosis of HCC cells by secreting interleukin-6 (IL-6), which induced autocrine insulin-like growth factor-1 (IGF-1) in HCC. IGF-1 promoted the progression and chemoresistance of HCC. IGF-1 receptor (IGF-1R) inhibitor NT157 abrogated the effect of CAF-derived IL-6 and autocrine IGF-1 on HCC. Mechanistic studies revealed that NT157 decreased IL-6-induced IGF-1 expression by inhibiting STAT3 phosphorylation and led to IRS-1 degradation, which mediated the proliferation of tumour by activating AKT signalling in ERK-dependent manner. Inhibition of IGF-1R also enhanced the therapeutic effect of sorafenib on HCC, especially chemoresistant tumours. STATEMENT OF SIGNIFICANCE: Our study showed IL-6-IGF-1 axis played crucial roles in the crosstalk between HCC and CAFs, providing NT157 inhibited of STAT3 and IGF-1R as a new targeted therapy in combination with sorafenib.

6.
Heliyon ; 10(12): e32600, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975089

RESUMEN

Objective: To optimise the dosing regimen of meropenem for treating Pseudomonas aeruginosa (PA) infections in critically ill patients with augmented renal clearance (ARC) using pharmacokinetic/pharmacodynamic (PK/PD) principles and Monte Carlo simulation (MCS). Methods: This research involves an MCS based on PK data from patients with ARC and a minimum inhibitory concentration (MIC) distribution of PA. This study simplifies the methods section, focusing on the critical aspects of simulation and target values for effective treatment. Results: The study highlights key findings and emphasises that tailored dosing based on bacterial MIC values is essential for patients with ARC. It also notes that empirical treatment in patients with ARC should consider the MIC distribution, with 2 g every (q) 6 h administered to achieve the PK/PD target, while 3 g q 6 h is effective in inhibiting resistance. Conclusion: Tailored dosing based on bacterial MIC values is crucial for patients with ARC. Prolonged infusion time alone does not enhance efficacy. Empirical treatment in patients with ARC should consider MIC distribution; a dosage of 2 g q 6 h achieves the PK/PD target, while 3 g q 6 h (≥12 g daily) inhibits resistance.

7.
BMC Pulm Med ; 24(1): 352, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030536

RESUMEN

BACKGROUND: This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). METHODS: This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. RESULTS: A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18-41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02-1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%. CONCLUSIONS: This study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Tomografía Computarizada por Rayos X , Humanos , Masculino , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/fisiopatología , Anciano , Estudios Prospectivos , Femenino , Factores de Riesgo , Persona de Mediana Edad , Progresión de la Enfermedad , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Modelos Logísticos , Hipertensión Pulmonar/diagnóstico por imagen , Curva ROC
8.
Heliyon ; 10(11): e31654, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38828289

RESUMEN

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

9.
Food Sci Nutr ; 12(6): 4443-4458, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873454

RESUMEN

The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification reaction, in order to produce an edible oil with a fatty acid ratio suitable for human needs. Initially, the optimal conditions for esterification were determined using the Box-Behnken design, with the measurement criterion being the content of ALA at the sn-2 position. The results indicated that the highest content of sn-2 ALA was obtained under the conditions of using 6.8 wt% Lipozyme®RMIM as the catalyst, a reaction temperature of 57°C, a reaction time of 3.3 h, and a substrate mass ratio of 5.6:4.4 for STF and FO. This led to the rapid breaking and recombining of molecular bonds, resulting in the interesterified fat (IF) with the highest content of ALA at the sn-2 position. Comparing STF and FO, IF exhibited excellent fatty acid composition and content. Furthermore, IF had a lower melting point and crystallization temperature compared to STF, and its solid fat content decreased with increasing temperature, completely melting at temperatures above 30°C. Thus, IF is a synthesized fat with excellent properties from both animal and vegetable sources.

10.
J Org Chem ; 89(13): 9543-9550, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38874168

RESUMEN

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

11.
J Clin Immunol ; 44(7): 155, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922539

RESUMEN

PURPOSE: Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype. METHODS: Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays. RESULTS: The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21low B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls. CONCLUSIONS: The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.


Asunto(s)
Dermatomiositis , Infecciones por Virus de Epstein-Barr , Proteínas de Microfilamentos , Mutación , Humanos , Masculino , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Dermatomiositis/genética , Dermatomiositis/diagnóstico , Dermatomiositis/inmunología , Niño , Proteínas de Microfilamentos/genética , Mutación/genética , Herpesvirus Humano 4 , Secuenciación del Exoma , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/diagnóstico , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Fenotipo , Linfocitos T/inmunología
12.
Artif Intell Med ; 153: 102888, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781870

RESUMEN

BACKGROUND: When treating patients with coronary artery disease and concurrent renal concerns, we often encounter a conundrum: how to achieve a clearer view of vascular details while minimizing the contrast and radiation doses during percutaneous coronary intervention (PCI). Our goal is to use deep learning (DL) to create a real-time roadmap for guiding PCI. To this end, segmentation, a critical first step, paves the way for detailed vascular analysis. Unlike traditional supervised learning, which demands extensive labeling time and manpower, our strategy leans toward semi-supervised learning. This method not only economizes on labeling efforts but also aims at reducing contrast and radiation exposure. METHODS AND RESULTS: CAG data sourced from eight tertiary centers in Taiwan, comprising 500 labeled and 8952 unlabeled images. Employing 400 labels for training and reserving 100 for validation, we built a U-Net based network within a teacher-student architecture. The initial teacher model was updated with 8952 unlabeled images inputted, employing a quality control strategy involving consistency regularization and RandAugment. The optimized teacher model produced pseudo-labels for label expansion, which were then utilized to train the final student model. We attained an average dice similarity coefficient of 0.9003 for segmentation, outperforming supervised learning methods with the same label count. Even with only 5 % labels for semi-supervised training, the results surpassed a supervised method with 100 % labels inputted. This semi-supervised approach's advantage extends beyond single-frame prediction, yielding consistently superior results in continuous angiography films. CONCLUSIONS: High labeling cost hinders DL training. Semi-supervised learning, quality control, and pseudo-label expansion can overcome this. DL-assisted segmentation potentially provides a real-time PCI roadmap and further diminishes radiation and contrast doses.


Asunto(s)
Vasos Coronarios , Aprendizaje Profundo , Aprendizaje Automático Supervisado , Humanos , Vasos Coronarios/diagnóstico por imagen , Intervención Coronaria Percutánea/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria/métodos , Procesamiento de Imagen Asistido por Computador/métodos
13.
Nat Prod Res ; : 1-5, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38813681

RESUMEN

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR (1H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.

14.
Exp Gerontol ; 191: 112434, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38636571

RESUMEN

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.


Asunto(s)
Densidad Ósea , Diabetes Mellitus Tipo 1 , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoporosis , Polimorfismo de Nucleótido Simple , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicaciones , Osteoporosis/genética , Densidad Ósea/genética , Factores de Riesgo , Femenino , Masculino , Cuello Femoral/diagnóstico por imagen , Predisposición Genética a la Enfermedad , Vértebras Lumbares , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Antebrazo
15.
J Clin Immunol ; 44(4): 102, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634985

RESUMEN

PURPOSE: Autoimmunity is a significant feature of APDS1 patients. We aimed to explore the pathogenic immune phenotype and possible mechanisms of autoimmunity in APDS1 patients. METHODS: The clinical records and laboratory data of 42 APDS1 patients were reviewed. Immunophenotypes were evaluated by multiparametric flow cytometry. Autoantibodies were detected via antigen microarray analysis. RESULTS: A total of 42 children with PIK3CD gene mutations were enrolled. Immunological tests revealed increased proportions of effector memory cells (86%) and central memory cells (59%) among CD4+ T cells; increased proportions of effector memory cells (83%) and terminally differentiated effector memory T cells (38%) among CD8+ T cells. Fewer CD3+ T cells and B cells and higher IgG levels were reported in patients with autoimmunity. The proportion of Tregs was decreased, and the proportions of Th9, Tfh, and Tfr cells were increased in APDS1 patients. Among APDS1 patients, higher proportion of Th2 and Tfr cells were found in those with autoimmunity. The proportions of CD11c+ B and CD21lo B cells in patients with autoimmunity were significantly increased. Antigen microarray analysis revealed a wide range of IgG/IgM autoantibodies in patients with APDS1. In patients with autoimmunity, the proportion of Tfr might be positively correlated with autoantibodies. CONCLUSIONS: The pathogenic immune phenotype of APDS1 patients included (1) deceased CD3+ T-cell and B-cell counts and increased IgG levels in patients with autoimmunity, (2) an imbalanced T helper cell subset, (3) increased proportions of autoreactive B cells, and (4) distinct autoantibody reactivities in patients with autoimmunity.


Asunto(s)
Autoanticuerpos , Autoinmunidad , Niño , Humanos , Linfocitos B , Fenotipo , Síndrome , Inmunoglobulina G
16.
Biochem Biophys Res Commun ; 714: 149964, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38669753

RESUMEN

Human DDX3X, an important member of the DEAD-box family RNA helicases, plays a crucial role in RNA metabolism and is involved in cancer development, viral infection, and neurodegenerative disease. Although there have been many studies on the physiological functions of human DDX3X, issues regarding its exact targets and mechanisms of action remain unclear. In this study, we systematically characterized the biochemical activities and substrate specificity of DDX3X. The results demonstrate that DDX3X is a bidirectional RNA helicase to unwind RNA duplex and RNA-DNA hybrid driven by ATP. DDX3X also has nucleic acid annealing activity, especially for DNA. More importantly, it can function as a typical nucleic acid chaperone which destabilizes highly structured DNA and RNA in an ATP-independent manner and promotes their annealing to form a more stable structure. Further truncation mutations confirmed that the highly disordered N-tail and C-tail are critical for the biochemical activities of DDX3X. They are functionally complementary, with the N-tail being crucial. These results will shed new light on our understanding of the molecular mechanism of DDX3X in RNA metabolism and DNA repair, and have potential significance for the development of antiviral/anticancer drugs targeting DDX3X.


Asunto(s)
Adenosina Trifosfato , ARN Helicasas DEAD-box , Chaperonas Moleculares , Humanos , Adenosina Trifosfato/metabolismo , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/genética , ADN/metabolismo , ADN/química , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , ARN/metabolismo , ARN/química , ARN/genética , Especificidad por Sustrato
17.
Acta Biochim Biophys Sin (Shanghai) ; 56(7): 986-996, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38655616

RESUMEN

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Biología Computacional , Epítopos de Linfocito T , Antígeno HLA-A2 , SARS-CoV-2 , Vacunas de ADN , Epítopos de Linfocito T/inmunología , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Animales , Vacunas de ADN/inmunología , Vacunas de ADN/genética , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/genética , Ratones , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Femenino , Ratones Endogámicos BALB C , Inmunoinformática
18.
J Org Chem ; 89(9): 6117-6125, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38654588

RESUMEN

The first paired electrolysis-enabled arylation of quinoxalin-2(1H)-ones was achieved using cyanoarenes as the arylation reagents. A variety of 3-arylquinoxalin-2(1H)-ones with various important functional groups were obtained in moderate to good yields under metal- and chemical oxidant-free conditions. With a pair of reductive and oxidative processes occurring among the substrates and reaction intermediates, the power consumption can be dramatically reduced.

19.
Opt Express ; 32(5): 7426-7447, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38439423

RESUMEN

A near-infrared single-photon lidar system, equipped with a 64×64 resolution array and a Risley prism scanner, has been engineered for daytime long-range and high-resolution 3D imaging. The system's detector, leveraging Geiger-mode InGaAs/InP avalanche photodiode technology, attains a single-photon detection efficiency of over 15% at the lidar's 1064 nm wavelength. This efficiency, in tandem with a narrow pulsed laser that boasts a single-pulse energy of 0.5 mJ, facilitates 3D imaging capabilities for distances reaching approximately 6 kilometers. The Risley scanner, composing two counter-rotating wedge prisms, is designed to perform scanning measurements across a 6-degree circular field-of-view. Precision calibration of the scanning angle and the beam's absolute direction was achieved using a precision dual-axis turntable and a collimator, culminating in 3D imaging with an exceptional scanning resolution of 28 arcseconds. Additionally, this work has developed a novel spatial domain local statistical filtering framework, specifically designed to separate daytime background noise photons from the signal photons, enhancing the system's imaging efficacy in varied lighting conditions. This paper showcases the advantages of array-based single-photon lidar image-side scanning technology in simultaneously achieving high resolution, a wide field-of-view, and extended detection range.

20.
Medicine (Baltimore) ; 103(6): e37033, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38335397

RESUMEN

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.


Asunto(s)
Carcinoma de Células Acinares , Neoplasias de la Tráquea , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Tráquea/cirugía , Neoplasias de la Tráquea/patología , Carcinoma de Células Acinares/cirugía , Carcinoma de Células Acinares/patología , Tráquea/cirugía , Tráquea/patología , Broncoscopía/métodos , Tomografía Computarizada por Rayos X
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA