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1.
Immunity ; 57(3): 513-527.e6, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38262419

RESUMEN

Accumulation of senescent cells in organs and tissues is a hallmark of aging and known to contribute to age-related diseases. Although aging-associated immune dysfunction, or immunosenescence, is known to contribute to this process, the underlying mechanism remains elusive. Here, we report that type 2 cytokine signaling deficiency accelerated aging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophages from senescence. Mechanistically, activated STAT6 promoted the expression of genes involved in DNA repair both via homologous recombination and Fanconi anemia pathways. Conversely, STAT6 deficiency induced release of nuclear DNA into the cytoplasm to promote tissue inflammation and organismal aging. Importantly, we demonstrate that IL-4 treatment prevented macrophage senescence and improved the health span of aged mice to an extent comparable to senolytic treatment, with further additive effects when combined. Together, our findings support that type 2 cytokine signaling protects macrophages from immunosenescence and thus hold therapeutic potential for improving healthy aging.


Asunto(s)
Senescencia Celular , Interleucina-4 , Animales , Ratones , Interleucina-4/metabolismo , Envejecimiento/genética , Macrófagos , Inflamación
2.
Development ; 149(5)2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35253855

RESUMEN

During mammalian brain development, how different astrocytes are specified from progenitor cells is not well understood. In particular, whether astrocyte progenitor cells (APCs) start as a relatively homogenous population or whether there is early heterogeneity remains unclear. Here, we have dissected subpopulations of embryonic mouse forebrain progenitors using single-cell transcriptome analyses. Our sequencing data revealed two molecularly distinct APC subgroups at the start of gliogenesis from both dorsal and ventral forebrains. The two APC subgroups were marked, respectively, by specific expression of Sparc and Sparcl1, which are known to function in mature astrocytes with opposing activities for regulating synapse formation. Expression analyses showed that SPARC and SPARCL1 mark APC subgroups that display distinct temporal and spatial patterns, correlating with major waves of astrogliogenesis during development. Our results uncover an early molecular divergence of APCs in the mammalian brain and provide a useful transcriptome resource for the study of glial cell specification.


Asunto(s)
Astrocitos/fisiología , Mamíferos/fisiología , Neurogénesis/fisiología , Neuroglía/fisiología , Células Madre/fisiología , Animales , Astrocitos/metabolismo , Diferenciación Celular/fisiología , Linaje de la Célula/fisiología , Proliferación Celular/fisiología , Mamíferos/metabolismo , Ratones , Células-Madre Neurales/metabolismo , Células-Madre Neurales/fisiología , Neuroglía/metabolismo , Osteonectina/metabolismo , Prosencéfalo/metabolismo , Prosencéfalo/fisiología , Análisis de la Célula Individual/métodos , Células Madre/metabolismo , Transcriptoma/fisiología
3.
Small ; : e2402748, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898734

RESUMEN

Defect engineering is considered as a flexible and effective mean to improve the performance of Fenton-like reactions. Herein, a simple method is employed to synthesize Co3O4 catalysts with Co-O vacancy pairs (VP) for peroxymonosulfate (PMS) activation. Multi-scaled characterization, experimental, and simulation results jointly revealed that the cation vacancies-VCo contributed to enhanced conductivity and anion vacancies-VO provided a new active center for the 1O2 generation. Co3O4-VP can optimize the O 2p and Co 3d bands with the strong assistance of synergistic double vacancies to reduce the reaction energy barrier of the "PMS → Co(IV) = O → 1O2" pathway, ultimately triggering the stable transition of mechanism. Co3O4-VP catalysts with radical-nonradical collaborative mechanism achieve the synchronous improvement of activity and stability, and have good environmental robustness to favor water decontamination applications. This result highlights the possibility of utilizing anion and cation vacancy engineering strategies to rational design Co3O4-based materials widely used in catalytic reactions.

4.
BMC Cancer ; 24(1): 716, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862951

RESUMEN

BACKGROUND: To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. METHODS: Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. RESULTS: Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05). CONCLUSIONS: The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.


Asunto(s)
Ganglios Linfáticos , Metástasis Linfática , Neoplasias del Recto , Tomografía Computarizada por Rayos X , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Masculino , Femenino , Persona de Mediana Edad , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Estudios Retrospectivos , Anciano , Tomografía Computarizada por Rayos X/métodos , Nomogramas , Adulto , Estadificación de Neoplasias , Anciano de 80 o más Años , Escisión del Ganglio Linfático
5.
J Magn Reson Imaging ; 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456745

RESUMEN

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) has recently emerged as hotspot in targeted therapy for urothelial bladder cancer (UBC). The HER2 status is mainly identified by immunohistochemistry (IHC), preoperative and noninvasive methods for determining HER2 status in UBC remain in searching. PURPOSES: To investigate whether radiomics features extracted from MRI using machine learning algorithms can noninvasively evaluate the HER2 status in UBC. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-five patients (age: 68.7 ± 10.5 years) with 14.3% females from January 2019 to May 2023 were divided into training (N = 156) and validation (N = 39) cohorts, and 43 patients (age: 67.1 ± 13.1 years) with 13.9% females from June 2023 to January 2024 constituted the test cohort (N = 43). FIELD STRENGTH/SEQUENCE: 3 T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo). ASSESSMENT: The HER2 status were assessed by IHC. Radiomics features were extracted from MRI images. Pearson correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were applied for feature selection, and six machine learning models were established with optimal features to identify the HER2 status in UBC. STATISTICAL TESTS: Mann-Whitney U-test, chi-square test, LASSO algorithm, receiver operating characteristic analysis, and DeLong test. RESULTS: Three thousand forty-five radiomics features were extracted from each lesion, and 22 features were retained for analysis. The Support Vector Machine model demonstrated the best performance, with an AUC of 0.929 (95% CI: 0.888-0.970) and accuracy of 0.859 in the training cohort, AUC of 0.886 (95% CI: 0.780-0.993) and accuracy of 0.846 in the validation cohort, and AUC of 0.712 (95% CI: 0.535-0.889) and accuracy of 0.744 in the test cohort. DATA CONCLUSION: MRI-based radiomics features combining machine learning algorithm provide a promising approach to assess HER2 status in UBC noninvasively and preoperatively. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

6.
J Magn Reson Imaging ; 59(4): 1179-1190, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37602726

RESUMEN

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. PURPOSE: To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. STUDY TYPE: Retrospective. POPULATION: A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT: Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T value = mean ADC tumor mean ADC muscle . The normalized ST value = mean ADC stalk mean ADC tumor . Three readers assessed the morphology of tumors and stalks. STATISTICAL TESTS: The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. RESULTS: In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. DATA CONCLUSION: This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Nomogramas , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Músculos/patología
7.
BJU Int ; 133(4): 442-450, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37983593

RESUMEN

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.


Asunto(s)
Verde de Indocianina , Neoplasias del Pene , Masculino , Humanos , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Estudios Prospectivos , Método Simple Ciego , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela
8.
Aging Male ; 27(1): 2363267, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38867423

RESUMEN

OBJECTIVE: To investigate the practical value of the transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH). METHODS: Consecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters. RESULTS: There were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA. CONCLUSIONS: The prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodos , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Estudios de Casos y Controles , Próstata/diagnóstico por imagen , Antígeno Prostático Específico/sangre
9.
Inorg Chem ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937959

RESUMEN

Type I photosensitizers offer an advantage in photodynamic therapy (PDT) due to their diminished reliance on oxygen levels, thus circumventing the challenge of hypoxia commonly encountered in PDT. In this study, we present the synthesis and comprehensive characterization of a novel type I photosensitizer derived from a cyclometalated Ir(III)-rhodamine complex. Remarkably, the complex exhibits a shift in absorption and fluorescence, transitioning from "off" to "on" states in aprotic and protic solvents, respectively, contrary to initial expectations. Upon exposure to light, the complex demonstrates the effective generation of O2- and ·OH radicals via the type I mechanism. Additionally, it exhibits notable photodynamic antibacterial activity against both Gram-positive and Gram-negative bacteria, demonstrated through in vitro and in vivo experiments. This research offers valuable insights for the development of novel type I photosensitizers.

10.
BMC Pregnancy Childbirth ; 24(1): 462, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965475

RESUMEN

BACKGROUND: The present work aimed to assess the value of mid-upper arm circumference (MUAC) at 8 to 12 weeks in predicting the occurrence of gestational diabetes mellitus (GDM). METHODS: According to eligibility criteria, 328 women with singleton pregnancies who underwent routine antenatal check-ups at Qinhuangdao Maternal and Child Health Hospital from September 2017 to September 2020 were included. The patients were divided into the gestational diabetes mellitus (GDM) and non-GDM groups according to oral glucose tolerance test (OGTT) data from gestation weeks 24 to 28. Clinical data were compared between the two groups. Logistic regression analysis was performed to determine factors independently predicting GDM. Receiver operating characteristic (ROC) curve analysis was employed to analyze the value of MUAC in predicting the occurrence of GDM. The optimal cut-off points were calculated. RESULTS: In logistic regression analysis, pre-pregnancy weight, waist circumference, MUAC, UA, TG, and HDL-C independently predicted the occurrence of GDM (P < 0.05). MUAC retained statistical significance upon adjustment for various confounders (OR = 8.851, 95%CI: 3.907-20.048; P < 0.001). ROC curve analysis revealed good diagnostic potential for MUAC in GDM (AUC = 0.742, 95%CI: 0.684-0.800, P < 0.001), with a cut-off of 28.5 cm, sensitivity and specificity were 61% and 77%, respectively. CONCLUSION: Pregnant women with MUAC >28.5 cm are prone to develop GDM during pregnancy, indicating that MUAC as an important predictive factor of GDM in early pregnancy.


Asunto(s)
Brazo , Diabetes Gestacional , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Femenino , Embarazo , Brazo/anatomía & histología , Adulto , Factores de Riesgo , Prueba de Tolerancia a la Glucosa , Valor Predictivo de las Pruebas , Curva ROC , Primer Trimestre del Embarazo , Modelos Logísticos
11.
Neurol Sci ; 45(7): 3411-3419, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38342839

RESUMEN

OBJECTIVE: To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C). METHOD: Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis. RESULT: Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy. CONCLUSION: Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.


Asunto(s)
Claustro , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Adolescente , Adulto Joven , Claustro/diagnóstico por imagen , Imagen por Resonancia Magnética , Niño , Síndromes Epilépticos , Encefalitis/diagnóstico por imagen , Encefalitis/diagnóstico , Encefalitis/complicaciones , Preescolar , Persona de Mediana Edad
12.
J Med Genet ; 60(8): 784-790, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36604176

RESUMEN

OBJECTIVES: To analyse the prevalence of pathogenic variants in DEPDC5, NPRL2 and NPRL3 that encode the GATOR1 (GTPase-activating protein towards the Rags 1) complex, a modulator in the mammalian target of rapamycin (mTOR) pathway, and to define the characteristics of GATOR1-associated epilepsy. METHODS: Clinical details and whole-exome sequencing data of 170 novel probands with lesional or non-lesional epilepsy were retrieved. Candidate variants in GATOR1 genes were verified by Sanger sequencing, and cosegregate analysis was performed. The pathogenicity of variants and their effect on mTOR signalling were investigated. RESULTS: Two novel frameshift variants and one recurrent nonsense variant were detected in DEPDC5, with a prevalence of 1.8% (3 out of 170) in the whole cohort and 3.1% (3 out of 97) in focal epilepsies. These variants cosegregated in pedigrees with epilepsy, respectively. Rare missense variants in NPRL2 and NPRL3 did not segregate with epilepsy in families, respectively. Epileptic phenotypes of 21 patients with DEPDC5 variants showed focal seizures with non-lesional variable foci that were predominantly sleep-related, with a median onset age of 10 years (range 1-30). Seizure outcome was variable. About 24% of patients were drug-resistant, and seizure attacks were absent in 33% of variant carriers. Of 13 patients who experienced seizures, 54% tended to resolve spontaneously. Functional assessments showed that the three variants affected DEPDC5 expression. These loss-of-function (LoF) variants affected the DEPDC5-dependent inhibition of mTOR. CONCLUSIONS: Patients carrying DEPDC5-LoF variants might show a high prevalence of focal seizures with a dynamic phenotype, indicating reduced penetrance and self-resolving features. The associated epilepsy was caused by loss of inhibition of the mTOR pathway. The pathogenicity of missense variants in GATOR1 genes should be cautiously evaluated.


Asunto(s)
Epilepsias Parciales , Epilepsia , Humanos , Epilepsias Parciales/genética , Epilepsia/epidemiología , Epilepsia/genética , Proteínas Activadoras de GTPasa/genética , Mutación/genética , Convulsiones/genética , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo
13.
Biomed Chromatogr ; 38(2): e5788, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081587

RESUMEN

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats. Plasma was prepared using a simple protein precipitation method by acetonitrile. Chromatographic separation of the analytes was achieved on a BEH C18 analytical column with a rapid 3.0 min run time and a flow rate of 0.5 ml/min. The calibration curves for plasma samples exhibited excellent linearity over a wide concentration range of 1.0-1,000 ng/ml for GFH009. Intra- and inter-day accuracies were within 92.7-105.7%, and precisions were no more than 6.7%. Furthermore, the analyte demonstrated stability under four different storage conditions, with variations of <15.0%. This study pioneers a methodological innovation by introducing a highly reliable, specific and sensitive analytical method for GFH009 in rat plasma. The successful application of this method in toxicokinetic studies further underscores its significance, offering valuable insights for the methodology of clinical pharmacokinetic research.


Asunto(s)
Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Ratas Sprague-Dawley , Cromatografía Liquida , Toxicocinética , Cromatografía Líquida de Alta Presión/métodos , Inhibidores de Proteínas Quinasas , Reproducibilidad de los Resultados
14.
J Integr Neurosci ; 23(5): 96, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38812382

RESUMEN

BACKGROUND: The states of the central nervous system (CNS) can be classified into subcritical, critical, and supercritical states that endow the system with information capacity, transmission capabilities, and dynamic range. A further investigation of the relationship between the CNS and the central pattern generators (CPG) is warranted to provide insight into the mechanisms that govern the locomotion system. METHODS: In this study, we established a fractional-order CPG model based on an extended Hindmarsh-Rose model with time delay. A CNS model was further established using a recurrent excitation-inhibition neuronal network. Coupling between these CNS and CPG models was then explored, demonstrating a potential means by which oscillations generated by a neural network respond to periodic stimuli. RESULTS AND CONCLUSIONS: These simulations yielded two key sets of findings. First, frequency sliding was observed when the CPG was sent to the CNS in the subcritical, critical, and supercritical states with different external stimulus and fractional-order index values, indicating that frequency sliding regulates brain function on multiple spatiotemporal scales when the CPG and CNS are coupled together. The main frequency range for these simulations was observed in the gamma band. Second, with increasing external inputs the coherence index for the CNS decreases, demonstrating that strong external inputs introduce neuronal stochasticity. Neural network synchronization is then reduced, triggering irregular neuronal firing. Together these results provide novel insight into the potential mechanisms that may underlie the locomotion system.


Asunto(s)
Encéfalo , Generadores de Patrones Centrales , Modelos Neurológicos , Generadores de Patrones Centrales/fisiología , Encéfalo/fisiología , Humanos , Animales , Redes Neurales de la Computación , Neuronas/fisiología , Simulación por Computador , Red Nerviosa/fisiología
15.
Genomics ; 115(5): 110692, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37532090

RESUMEN

Accumulating evidence has proven that circRNAs play vital roles in tumor progression. Nevertheless, the mechanisms underlying circRNAs in bladder cancer (BCa) remain largely unknown. The purpose of this study was to identify the role and investigate the potential molecular mechanisms of hsa_circ_0003098 in BCa. We confirmed that hsa_circ_0003098 expression was significantly upregulated in BCa tissues, of which expression was remarkably associated with poor prognosis. Functionally, overexpression of hsa_circ_0003098 promoted BCa cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. Mechanistically, hsa_circ_0003098 promoted upregulation of ACAT2 expression and induced cholesteryl ester accumulation via acting as a sponge for miR-377-5p. Thus, hsa_circ_0003098 plays an oncogenic role in BCa and may serve as a potential biomarker and therapeutic target for BCa.

16.
Sensors (Basel) ; 24(6)2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38544033

RESUMEN

In order to mitigate the risk of roof-dominated coal burst in underground coal mining, horizontal long borehole staged hydraulic fracturing technology has been prevailingly employed to facilitate the weakening treatment of the hard roof in advance. Such weakening effect, however, can hardly be evaluated, which leads to a lack of a basis in which to design the schemes and parameters of hydraulic fracturing. In this study, a combined underground-ground integrated microseismic monitoring and transient electromagnetic detection method was utilized to carry out simultaneous evaluations of the seismic responses to each staged fracturing and the apparent resistivity changes before and after all finished fracturing. On this basis, the comparable and applicable fracturing effects on coal burst prevention were evaluated and validated by the distribution of microseismic events and their energy magnitude during the mining process. Results show that the observed mining-induced seismic events are consistent with the evaluation results obtained from the combined seismic-electromagnetic detection method. However, there is a limited reduction effect on resistivity near the fractured section that induces far-field seismic events. Mining-induced seismic events are concentrated primarily within specific areas, while microseismic events in the fractured area exhibit high frequency but low energy overall. This study validates the rationality of combined seismic-electromagnetic detection results and provides valuable insights for optimizing fracturing construction schemes as well as comprehensively evaluating outcomes associated with underground directional long borehole staged hydraulic fracturing.

17.
J Clin Ultrasound ; 52(2): 105-111, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37930057

RESUMEN

OBJECTIVES: Ultrasound medical reports are an important means of diagnosing diseases and assessing treatment effectiveness. However, their professional terms and complex sentences often make it difficult for ordinary people to understand. Therefore, this study explores the clinical value of using artificial intelligence systems based on ChatGPT to interpret ultrasound medical reports. METHODS: In this study, a combination of online and offline questionnaires were used to survey both physicians and non-medical individuals. The questionnaires evaluated ChatGPT's interpretation of ultrasound reports from both professional and comprehensibility perspectives, and the results were analyzed using Excel spreadsheets. Additionally, a portion of the research content was evaluated using the Likert Scale 5-point method in the questionnaire. RESULTS: According to survey results, 67.4% of surveyed doctors believe that using ChatGPT for interpreting ultrasound medical reports can help improve work efficiency. At the same time, 69.72% of non-medical professionals believe it is necessary to enhance their understanding of medical ultrasound reports through ChatGPT interpretation, and 62.58% support the application of ChatGPT to ultrasound medical reports. The non-medical group's understanding of ultrasound medical reports significantly improved (p < 0.01) after implementing ChatGPT, However, 67.49% of the general public are concerned about ChatGPT's imperfect functionality, which may cause misleading information. This reflects that the public's trust in new technology is not high enough, and they are also worried about possible privacy leaks and security issues with ChatGPT technology. CONCLUSIONS: The higher acceptance and support of non-medical individuals for the interpretation of medical reports by ChatGPT might be due to the system's natural language processing abilities that allow them to better understand and evaluate report contents. However, the expertise and experience of physicians are still irreplaceable. This suggests that the ChatGPT-based ultrasound medical report interpretation system has certain clinical value and application prospects, but further optimization is necessary to address its shortcomings in data quality and professionalism. This study provides a reference and inspiration for promoting the application and development of ultrasound technology and artificial intelligence systems in the medical field.


Asunto(s)
Inteligencia Artificial , Médicos , Humanos , Ultrasonido , Exactitud de los Datos
18.
Int J Mol Sci ; 25(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38791209

RESUMEN

Nanoparticles (NPs) are extremely important tools to overcome the limitations imposed by therapeutic agents and effectively overcome biological barriers. Smart designed/tuned nanostructures can be extremely effective for cancer treatment. The selection and design of nanostructures and the adjustment of size and surface properties are extremely important, especially for some precision treatments and drug delivery (DD). By designing specific methods, an important era can be opened in the biomedical field for personalized and precise treatment. Here, we focus on advances in the selection and design of nanostructures, as well as on how the structure and shape, size, charge, and surface properties of nanostructures in biological fluids (BFs) can be affected. We discussed the applications of specialized nanostructures in the therapy of head and neck cancer (HNC), which is a difficult and aggressive type of cancer to treat, to give an impetus for novel treatment approaches in this field. We also comprehensively touched on the shortcomings, current trends, and future perspectives when using nanostructures in the treatment of cancer.


Asunto(s)
Nanoestructuras , Humanos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Nanopartículas/química , Nanopartículas/uso terapéutico , Animales
19.
Adv Funct Mater ; 33(33)2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37601745

RESUMEN

Different tissues have complex anisotropic structures to support biological functions. Mimicking these complex structures in vitro remains a challenge in biomaterials designs in support of tissue regeneration. Here, inspired by different types of silk nanofibers, a composite materials strategy was pursued towards this challenge. A combination of fabrication methods was utilized to achieve separate control of amorphous and beta-sheet rich silk nanofibers in the same solution. Aqueous solutions containing these two structural types of silk nanofibers were then simultaneously treated with an electric field and with ethylene glycol diglycidyl ether (EGDE). Under these conditions, the beta-sheet rich silk nanofibers in the mixture responded to the electric field while the amorphous nanofibers were active in the crosslinking process with the EGDE. As a result, cryogels with anisotropic structures were prepared, including mimics for cortical- and cancellous-like bone biomaterials as a complex osteoinductive niche. In vitro studies revealed that mechanical cues of the cryogels induced osteodifferentiation of stem cells while the anisotropy inside the cryogels influenced immune reactions of macrophages. These bioactive cryogels also stimulated improved bone regeneration in vivo through modulation of inflammation, angiogenesis and osteogenesis responses, suggesting an effective strategy to develop bioactive matrices with complex anisotropic structures beneficial to tissue regeneration.

20.
Small ; 19(42): e2302744, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37322373

RESUMEN

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.


Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Neoplasias Hepáticas , Humanos , Especies Reactivas de Oxígeno , Hipoxia , Oxígeno , Neoplasias Hepáticas/terapia , Catálisis , Línea Celular Tumoral , Microambiente Tumoral
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