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1.
BMC Gastroenterol ; 24(1): 276, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164628

RESUMEN

BACKGROUND: The association between marital status and gallbladder cancer (GBC) remains uncertain. This study aimed to verify the relationship between marital status and GBC and construct a prognostic nomogram to predict the impact of marital status on GBC patients. METHOD: GBC patients were divided into married and unmarried groups using data from the Surveillance, Epidemiology, and End Results (SEER) database. We employed competing risk analyses, propensity score matching (PSM), and Kaplan-Meier survival analyses. The relationship between marital status and GBC was then verified, and the predicted nomogram was constructed. RESULTS: A total of 3913 GBC patients were obtained from the SEER database, and an additional 76 GBC patients from Hangzhou Traditional Chinese Medicine Hospital were selected as the external validation group. The competing risk analysis revealed a significant disparity in the 5-year cumulative incidence of cancer-specific death (CSD) between the two cohorts (59.1% vs. 65.2%, p = 0.003). Furthermore, the multivariate competing hazards regression analysis identified a significant association (HR, 1.17; 95% CI, 1.04-1.31; p = 0.007) between marital status and CSD. To assess the 1-, 3-, and 5-year risks of CSD, a comprehensive competing event nomogram was constructed using factors derived from the multivariate analysis. The area under the receiver operating characteristic curve (AUC) values for the 1-, 3-, and 5-year training cohorts were 0.806, 0.785, and 0.776, respectively. In the internal validation cohort, these values were 0.798, 0.790, and 0.790, while the external validation cohort exhibited AUC values of 0.748, 0.835, and 0.883 for the corresponding time intervals. Furthermore, calibration curves demonstrated a commendable level of concordance between the observed and predicted probabilities of CSD. CONCLUSION: Marriage was a protective factor for GBC patients after taking competing risk into consideration. The proposed nomogram demonstrated exceptional predictive power.


Asunto(s)
Neoplasias de la Vesícula Biliar , Estimación de Kaplan-Meier , Estado Civil , Nomogramas , Programa de VERF , Humanos , Neoplasias de la Vesícula Biliar/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Anciano , Pronóstico , Puntaje de Propensión , Factores de Riesgo , China/epidemiología
2.
J Integr Neurosci ; 23(8): 147, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39207073

RESUMEN

BACKGROUND: Shingles can cause long-term pain and negative emotions, along with changes in brain function. In this study, Granger Causality Analysis (GCA) was used to compare herpes zoster (HZ) and postherpetic neuralgia (PHN) differences in effective connections within the "pain matrix" between patients and healthy controls to further understand patterns of interaction between brain regions and explore the relationship between changes in effective connections and clinical features. METHODS: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 55 HZ; 55 PHN; and 50 age-, sex- matched healthy controls (HCs). The brain regions associated with the pain matrix are used as the seeds of effective connectivity. GCA was used to analyze effective connections in brain regions that differed significantly between groups. Then the correlation between GCA values and clinical indicators was studied. RESULTS: Compared with HC, GCA values between the thalamus and the amygdala, between the thalamus and the precentral gyrus, from the thalamus to the postcentral gyrus, and from the parahippocampal gyrus to the amygdala, anterior cingulate gyrus were significantly reduced in HZ patients. Compared with HC, GCA values between the insular and the postcentral gyrus, from the insular to the inferior parietal lobe, and from the postcentral gyrus to the amygdala were significantly reduced in PHN patients. Compared with HZ, GCA values between the inferior parietal lobe and the parahippocampal gyrus, between the inferior parietal lobe and the anterior cingulate gyrus, and from the anterior cingulate gyrus to the amygdala were significantly increased in PHN patients. The visual analogue scale (VAS) score of PHN patients was positively correlated with the GCA value from the central posterior lobe to the insula. CONCLUSIONS: PHN and HZ patients showed a broad reduction in effective connections, mainly reflected in abnormal pain pathway regulation, pain perception, negative emotion and memory production, providing new perspectives to understand the neuroimaging mechanisms of shingles.


Asunto(s)
Herpes Zóster , Imagen por Resonancia Magnética , Neuralgia Posherpética , Humanos , Neuralgia Posherpética/diagnóstico por imagen , Neuralgia Posherpética/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Herpes Zóster/diagnóstico por imagen , Herpes Zóster/complicaciones , Herpes Zóster/fisiopatología , Anciano , Adulto , Conectoma , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología
4.
Small ; : e2401995, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818678

RESUMEN

Upgrading thermosetting polymer waste and harvesting unwanted electromagnetic energy are of great significance in solving environmental pollution and energy shortage problems. Herein, inspired by the glass-blowing art, a spontaneous, controllable, and scalable strategy is proposed to prepare hollow carbon materials by inner blowing and outside blocking. Specifically, hierarchically neuron-like hollow carbon materials (HCMSs) with various sizes are fabricated from melamine-formaldehyde sponge (MS) waste. Benefiting from the synergistic of the hollow "cell body" and the connected "protrusions" networks, HCMSs reveal superior electromagnetic absorption performance with a strong reflection loss of -54.9 dB, electromagnetic-heat conversion ability with a high conversion efficiency of 34.4%, and efficient energy storage performance in supercapacitor. Furthermore, a multifunctional device integrating electromagnetic-heat-electrical energy conversion is designed, and its feasibility is proved by experiments and theoretical calculations. The integrated device reveals an output voltage of 34.5 mV and a maximum output power of 0.89 µW with electromagnetic radiation for 60 s. This work provides a novel solution to recycle polymer waste, electromagnetic energy, and unwanted thermal energy.

5.
Oncogene ; 43(21): 1644-1653, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38594504

RESUMEN

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.


Asunto(s)
Ferroptosis , Lanosterol , Células Madre Mesenquimatosas , Mieloma Múltiple , Mieloma Múltiple/patología , Mieloma Múltiple/metabolismo , Animales , Lanosterol/farmacología , Humanos , Ratones , Células Madre Mesenquimatosas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Hierro/metabolismo , Transducción de Señal
6.
Br J Haematol ; 204(6): 2275-2286, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38639201

RESUMEN

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations. Cox regression analysis unveiled key antigens influencing the prognosis of AML patients. In terms of underlying genotypes, we observed that the antigenic profiles and outcomes of one specific group, primarily composed of CBFA2T3::GLIS2 and FUS::ERG, were analogous to the reported RAM phenotype. Overall, our data highlight the significance of immunophenotype to tailor treatment for paediatric AML.


Asunto(s)
Inmunofenotipificación , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Niño , Preescolar , Femenino , Masculino , Adolescente , Lactante , Pronóstico , Citometría de Flujo
7.
Cancer Lett ; 591: 216880, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38621457

RESUMEN

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.


Asunto(s)
Biomarcadores de Tumor , Leucemia Mieloide Aguda , ARN Circular , Pronóstico , Humanos , Niño , ARN Circular/análisis , Biomarcadores de Tumor/análisis , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Análisis de Secuencia de ARN , Conjuntos de Datos como Asunto , Análisis de Supervivencia , Células K562 , Supervivencia sin Progresión , Resultado del Tratamiento , Preescolar , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica
8.
Sci Total Environ ; 926: 171661, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38490427

RESUMEN

Human bioaerosols contribute significantly to indoor air quality. This study used a Wideband Integrated Bioaerosol Sensor (WIBS-4A) instrument for real-time measurement of particle size distribution and count to differentiate fluorescent bioaerosols from non-fluorescent aerosols. Through an experiment involving 12 subjects (six men and six women) wearing standard cotton clothing in a 2 m × 2 m × 2 m environmental chamber, we established a quantitative method to obtain the bioaerosol emission rate of a single subject, aiming to explore the effects of masks and sex on bioaerosol emissions from different individuals. The mean emission rates of fluorescent bioaerosols in the particle size ranges of 0.5-2.5 µm and 2.5-10 µm were 3.192±2.11×104 counts/(person·h) and 13.98±9.34×104 counts/(person·h), respectively. A comparison between those wearing and not wearing masks revealed no significant differences in the emissions of fluorescent bioaerosols. This suggests respiratory sources may not significantly impact the emissions of fluorescent bioaerosols from individuals under seated breathing conditions. Significant disparities in the fluorescent bioaerosol emission rates of different biological sexes were observed through independent sample analysis. Males exhibited 41 % and 15 % higher emission rates than females for particle size ranges of 0.5-2.5 µm and 2.5-10 µm, respectively, possibly because of different metabolic rates. A significant correlation between metabolic rates and fluorescent bioaerosols (sig = 0.044 < 0.05) was observed in all the subjects. These findings underscore the individual variations that affect bioaerosol emission rates. The data provided by this study will facilitate further analysis of the on-site measured data and source analysis.


Asunto(s)
Contaminación del Aire Interior , Monitoreo del Ambiente , Humanos , Femenino , Monitoreo del Ambiente/métodos , Contaminación del Aire Interior/análisis , Tamaño de la Partícula , Aerosoles/análisis , Microbiología del Aire
9.
Br J Haematol ; 204(4): 1354-1366, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38432257

RESUMEN

This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high-dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady-state MTX concentrations (<56 µmol/L) and poorer outcomes in intermediate-/high-risk (IR/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with MLL rearrangements. In contrast, such an association did not emerge within the low-risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation-based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200 mg/kg dosage for infants under 1 year. The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower-risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady-state concentrations within the optimal range.


Asunto(s)
Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Lactante , Humanos , Antimetabolitos Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Pronóstico , Factores de Riesgo
10.
Plants (Basel) ; 13(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38337939

RESUMEN

Sugars act as the main energy sources in many fruit and vegetable crops. The biosynthesis and transportation of sugars are crucial and especially contribute to growth and development. SWEET is an important gene family that plays a vital role in plants' growth, development, and adaptation to various types of stresses (biotic and abiotic). Although SWEET genes have been identified in numerous plant species, there is no information on SWEETs in Potentilla anserina. In the present study, we performed a comprehensive genome-wide bioinformatics analysis and identified a total of 23 candidate PaSWEETs genes in the Potentilla anserina genome, which were randomly distributed on ten different chromosomes. The phylogenetic analysis, chromosomal location, gene structure, specific cis-elements, protein interaction network, and physiological characteristics of these genes were systematically examined. The identified results of the phylogenetic relationship with Arabidopsis thaliana revealed that these PaSWEET genes were divided into four clades (I, II, III, and IV). Moreover, tissue-specific gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) validation exposed that the identified PaSWEETs were differentially expressed in various tissues (roots, stems, leaves, and flowers). Mainly, the relative fold gene expression in swollen and unswollen tubers effectively revealed that PaSWEETs (7, 9, and 12) were highly expressed (300-, 120-, and 100-fold) in swollen tubers. To further elucidate the function of PaSWEETs (7, 9, and 12), their subcellular location was confirmed by inserting them into tobacco leaves, and it was noted that these genes were present on the cell membrane. On the basis of the overall results, it is suggested that PaSWEETs (7, 9, and 12) are the candidate genes involved in swollen tuber formation in P. anserina. In crux, we speculated that our study provides a valuable theoretical base for further in-depth function analysis of the PaSWEET gene family and their role in tuber development and further enhancing the molecular breeding of Potentilla anserina.

11.
Curr Med Chem ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38362683

RESUMEN

AIMS: The aims of this study were to determine hub genes in glaucoma through multiple machine learning algorithms. BACKGROUND: Glaucoma has afflicted many patients for many years, with excessive pressure in the eye continuously damaging the nervous system and leading to severe blindness. An effective molecular diagnostic method is currently lacking. OBJECTIVE: The present study attempted to reveal the molecular mechanism and gene regulatory network of hub genes in glaucoma, followed by an attempt to reveal the drug-gene-disease network regulated by hub genes. METHODS: A microarray sequencing dataset (GSE9944) was obtained through the Gene Expression Omnibus database. The differentially expressed genes in Glaucoma were identified. Based on these genes, we constructed three machine learning models for feature training, Random Forest model (RF), Least absolute shrinkage and selection operator regression model (LASSO), and Support Vector Machines model (SVM). Meanwhile, Weighted Gene Co-Expression Network Analysis (WGCNA) was performed for GSE9944 expression profiles to identify Glaucoma-related genes. The overlapping genes in the four groups were considered as hub genes of Glaucoma. Based on these genes, we also constructed a molecular diagnostic model of Glaucoma. In this study, we also performed molecular docking analysis to explore the gene-drug network targeting hub genes. In addition, we evaluated the immune cell infiltration landscape in Glaucoma samples and normal samples by applying CIBERSORT method. RESULTS: 8 hub genes were determined: ATP6V0D1, PLEC, SLC25A1, HRSP12, PKN1, RHOD, TMEM158 and GSN. The diagnostic model showed excellent diagnostic performance (area under the curve=1). GSN might positively regulate T cell CD4 naïve as well as negatively regulate T cell regulation (Tregs). In addition, we constructed gene-drug networks in an attempt to explore novel therapeutic agents for Glaucoma. CONCLUSION: Our results systematically determined 8 hub genes and established a molecular diagnostic model that allowed the diagnosis of Glaucoma. Our study provided a basis for future systematic studies of Glaucoma pathogenesis.

12.
PLoS One ; 19(1): e0292895, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38266030

RESUMEN

BACKGROUND: The research aimed to construct a novel predictive nomogram to identify specific metastatic gastric adenocarcinoma (mGAC) populations who could benefit from primary tumor resection (PTR). METHOD: Patients with mGAC were included in the SEER database and divided into PTR and non-PTR groups. The Kaplan-Meier analysis, propensity score matching (PSM), least absolute shrink and selection operator (LASSO) regression, multivariable logistic regression, and multivariate Cox regression methods were then used. Finally, the prediction nomograms were built and tested. RESULTS: 3185 patients with mGAC were enrolled. Among the patients, 679 cases underwent PTR while the other 2506 patients didn't receive PTR. After PSM, the patients in the PTR group presented longer median overall survival (15.0 vs. 7.0 months, p < 0.001). Among the PTR group, 307 (72.9%) patients obtained longer overall survival than seven months (beneficial group). Then the LASSO logistic regression was performed, and gender, grade, T stage, N stage, pathology, and chemotherapy were included to construct the nomogram. In both the training and validation cohorts, the nomogram exhibited good discrimination (AUC: 0.761 and 0.753, respectively). Furthermore, the other nomogram was constructed to predict 3-, 6-, and 12-month cancer-specific survival based on the variables from the multivariate Cox analysis. The 3-, 6-, and 12-month AUC values were 0.794, 0.739, and 0.698 in the training cohort, and 0.805, 0.759, and 0.695 in the validation cohorts. The calibration curves demonstrated relatively good consistency between the predicted and observed probabilities of survival in two nomograms. The models' clinical utility was revealed through decision curve analysis. CONCLUSION: The benefit nomogram could guide surgeons in decision-making and selecting optimal candidates for PTR among mGAC patients. And the prognostic nomogram presented great prediction ability for these patients.


Asunto(s)
Adenocarcinoma , Cirujanos , Humanos , Investigación , Adenocarcinoma/cirugía , Calibración , Puntaje de Propensión
13.
Endocrine ; 83(1): 118-126, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37542676

RESUMEN

OBJECTIVE: To investigate the application of machine learning (ML) model-based thyroid ultrasound radiomics in the evaluation of malignancy in partially cystic thyroid nodules (PCTNs). METHODS: One hundred and ninety-two patients with 197 nodules PCTNs from January 2020 to December 2020 were retrospectively analyzed. Radiomics features were extracted based on hand-crafted features from the ultrasound images, and machine learning methods were used to build a classification model by radiomics features. The least absolute shrinkage and selection operator regression was applied to select the features of nonzero coefficients from radiomics features. The prediction performance of the established model was mainly evaluated by the area under the curve (AUC) and accuracy, sensitivity, and specificity. RESULTS: Nineteen radiomics features were extracted from the original images for each nodule. Eight ML classifiers were able to differentiate malignancy in PCTNs. The AUC, accuracy, sensitivity, and specificity of k-Nearest Neighbor (KNN) model were 0.909, 82.95%, 83.33%, and 89.90%, respectively, on the test cohort. The comparative result showed statistically equivalent performance for thyroid nodule diagnosis based on image fusion and single image. In addition, the ML-Based ultrasound radiomics system showed a better AUC as compared with ACR TI-RADS model and the ultrasound features model. CONCLUSION: The novel ultrasonic-based ML model has an important clinical value for predicting malignancy in PCTNs. It can provide clinicians with a preoperative non-invasive primary screening method for PCTN diagnosis to avoid unnecessary medical investment and improve treatment outcomes.


Asunto(s)
Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Estudios Retrospectivos , Radiómica , Ultrasonografía/métodos , Aprendizaje Automático
14.
Small ; 20(12): e2307408, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37940624

RESUMEN

Nitrogen-doped titanium carbides (MXene) films exhibit extraordinary volumetric capacitance when high-concentration sulfuric acid electrolyte is utilized owing to the enhancement of pseudocapacitance. However, the energy storage mechanism of nitrogen-doped MXene is unclear due to the complex electrode structure and electrolyte ions' behavior. Here, based on pristine MXene (Ti3C2O2), three different MXene structures are constructed by introducing metal vacancy sites and doped nitrogen atoms, namely, defective MXene (Ti2.9C2O2), nitrogen-doped MXene (Ti3C2O1.9N0.1), and nitrogen-doped MXene with metal vacancy sites (Ti2.9C2O1.9N0.1). Then, the density functional theory (DFT)-based calculations coupled with the effective screening medium reference interaction site method (ESM-RISM) are applied to reveal the electrochemical behavior at the electrode/electrolyte interfacial area. Through analyzing the electronic structure, electrical double-layer capacitance (EDLC), and equilibrium potential of the pseudocapacitance reaction, the specific effect of structural changes on their performance can be clarified: metal vacancy sites can reduce the potential difference of gap layer (Outer Helmholtz plane) at charged state and increase the electronic capacity of Ti, which can be used to explain the high pseudocapacitance, low charge transfer resistance and high-rate capacity properties of nitrogen-doped MXene observed in experiments.

16.
Nat Commun ; 14(1): 6792, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880218

RESUMEN

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Cromatina/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Recurrencia , Transformación Celular Neoplásica
17.
ACS Nano ; 17(19): 19323-19337, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37769163

RESUMEN

Insulating thermally conductive polymer composites are in great demand in integrated-circuit packages, for efficient heat dissipation and to alleviative short-circuit risk. Herein, the continuous oriented hexagonal boron nitride (h-BN) frameworks (o-BN@SiC) were prepared via self-assembly and in situ chemical vapor infiltration (CVI) interface welding. The insulating o-BN@SiC/epoxy (o-BN@SiC/EP) composites exhibited enhanced thermal conductivity benefited from the CVI-SiC-welded BN-BN interface. Further, multiscale simulation, combining first-principles calculation, Monte Carlo simulation, and finite-element simulation, was performed to quantitatively reveal the effect of the welded BN-BN interface on the heat transfer of o-BN@SiC/EP composites. Phonon transmission in solders and phonon-phonon coupling of filler-solder interfaces enhanced the interfacial heat transfer between adjacent h-BN microplatelets, and the interfacial thermal resistance of the dominant BN-BN interface was decreased to only 3.83 nK·m2/W from 400 nK·m2/W, plunging by over 99%. This highly weakened interfacial thermal resistance greatly improved the heat transfer along thermal pathways and resulted in a 26% thermal conductivity enhancement of o-BN@SiC/EP composites, compared with physically contacted oriented h-BN/EP composites, at 15 vol % h-BN. This systematic multiscale simulation broke through the barrier of revealing the heat transfer mechanism of polymer composites from the nanoscale to the macroscale, which provided rational cognition about the effect of the interfacial thermal resistance between fillers on the thermal conductivity of polymer composites.

18.
Cancer Immunol Res ; 11(10): 1384-1399, 2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37586075

RESUMEN

In multiple myeloma (MM), bone marrow stromal cells (BMSC) shape a unique niche within the bone marrow, promoting T-cell dysfunction and driving MM progression; however, the precise underlying mechanisms remain elusive. Here, we show that BMSC-mediated reprogramming of MM cells led to heightened production of CXCL10. CXCL10 orchestrated the recruitment of γδ T cells into the bone marrow, and this was observed in both the Vk*MYC and 5TGM1 mouse models of MM, as well as in patients experiencing refractory or relapsed MM. Furthermore, the dysfunctional γδ T cells in the MM bone marrow niche exhibited increased PD-1 expression and IL17 production. In the Vk*MYC mouse model, MM-associated bone lesions and mortality were markedly alleviated in Tcrd-/- mice, and MM disease progression could be rescued in these mice upon transplantation of γδ T cells expanded from wild-type mice, but not from Il17-/- mice. Mechanistically, the hypoxic microenvironment prevailing in the MM bone marrow niche stimulated the expression of steroid receptor coactivator 3 (SRC-3) in γδ T cells, which in turn interacted with the transcriptional factor RORγt, promoting Il17 transcription. Pharmacologic inhibition of SRC-3 utilizing SI-2 effectively suppressed Il17A expression in γδ T cells, leading to alleviation of MM progression in the murine models and enhancing the anti-multiple myeloma efficacy of bortezomib. Our results illuminated the bone marrow microenvironment's involvement in provoking γδ T-cell dysfunction throughout MM progression and suggest SRC-3 inhibition as a promising strategy to enhance the effectiveness of immunotherapies targeting γδ T cells.


Asunto(s)
Mieloma Múltiple , Humanos , Ratones , Animales , Mieloma Múltiple/patología , Médula Ósea/patología , Bortezomib , Receptores de Antígenos de Linfocitos T gamma-delta , Modelos Animales de Enfermedad , Linfocitos T/metabolismo , Microambiente Tumoral , Quimiocina CXCL10
19.
BMC Gastroenterol ; 23(1): 238, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452300

RESUMEN

BACKGROUND: Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients. METHODS: Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P < 0.001), respectively. In 1-, 3-, and 5-year CSS prediction using DCA curves, the nomogram outperformed the AJCC staging system. The nomogram performed well in both the internal and external validation cohorts. CONCLUSION: We developed and validated a nomogram to predict 1-, 3-, and 5-year CSS for GNEC patients after surgical resection. This well-performing model could help doctors enhance the treatment plan.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias Gástricas , Humanos , Nomogramas , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Carcinoma Neuroendocrino/cirugía , Medición de Riesgo , Pronóstico
20.
Sensors (Basel) ; 23(10)2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37430832

RESUMEN

Acoustic vector sensor (AVS) is a kind of sensor widely used in underwater detection. Traditional methods use the covariance matrix of the received signal to estimate the direction-of-arrival (DOA), which not only loses the timing structure of the signal but also has the problem of weak anti-noise ability. Therefore, this paper proposes two DOA estimation methods for underwater AVS arrays, one based on a long short-term memory network and attention mechanism (LSTM-ATT), and the other based on Transformer. These two methods can capture the contextual information of sequence signals and extract features with important semantic information. The simulation results show that the two proposed methods perform much better than the multiple signal classification (MUSIC) method, especially in the case of low signal-to-noise ratio (SNR), the DOA estimation accuracy has been greatly improved. The accuracy of the DOA estimation method based on Transformer is comparable to that of the DOA estimation method based on LSTM-ATT, but the computational efficiency is obviously better than that of the DOA estimation method based on LSTM-ATT. Therefore, the DOA estimation method based on Transformer proposed in this paper can provide a reference for fast and effective DOA estimation under low SNR.

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