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1.
Nature ; 626(8000): 864-873, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38326607

RESUMEN

Macrophage activation is controlled by a balance between activating and inhibitory receptors1-7, which protect normal tissues from excessive damage during infection8,9 but promote tumour growth and metastasis in cancer7,10. Here we report that the Kupffer cell lineage-determining factor ID3 controls this balance and selectively endows Kupffer cells with the ability to phagocytose live tumour cells and orchestrate the recruitment, proliferation and activation of natural killer and CD8 T lymphoid effector cells in the liver to restrict the growth of a variety of tumours. ID3 shifts the macrophage inhibitory/activating receptor balance to promote the phagocytic and lymphoid response, at least in part by buffering the binding of the transcription factors ELK1 and E2A at the SIRPA locus. Furthermore, loss- and gain-of-function experiments demonstrate that ID3 is sufficient to confer this potent anti-tumour activity to mouse bone-marrow-derived macrophages and human induced pluripotent stem-cell-derived macrophages. Expression of ID3 is therefore necessary and sufficient to endow macrophages with the ability to form an efficient anti-tumour niche, which could be harnessed for cell therapy in cancer.


Asunto(s)
Proteínas Inhibidoras de la Diferenciación , Macrófagos del Hígado , Neoplasias , Animales , Humanos , Ratones , Células de la Médula Ósea/citología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Linaje de la Célula , Células Madre Pluripotentes Inducidas/citología , Proteínas Inhibidoras de la Diferenciación/deficiencia , Proteínas Inhibidoras de la Diferenciación/genética , Proteínas Inhibidoras de la Diferenciación/metabolismo , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Macrófagos del Hígado/citología , Macrófagos del Hígado/inmunología , Macrófagos del Hígado/metabolismo , Hígado/inmunología , Hígado/patología , Activación de Macrófagos , Proteínas de Neoplasias , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Fagocitosis
2.
Exp Cell Res ; 436(1): 113956, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38341081

RESUMEN

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Vía de Señalización Hippo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Compuestos de Fenilurea/farmacología
3.
Cereb Cortex ; 34(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38869374

RESUMEN

The central sulcus divides the primary motor and somatosensory cortices in many anthropoid primate brains. Differences exist in the surface area and depth of the central sulcus along the dorso-ventral plane in great apes and humans compared to other primate species. Within hominid species, there are variations in the depth and aspect of their hand motor area, or knob, within the precentral gyrus. In this study, we used post-image analyses on magnetic resonance images to characterize the central sulcus shape of humans, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus and Pongo abelii). Using these data, we examined the morphological variability of central sulcus in hominids, focusing on the hand region, a significant change in human evolution. We show that the central sulcus shape differs between great ape species, but all show similar variations in the location of their hand knob. However, the prevalence of the knob location along the dorso-ventral plane and lateralization differs between species and the presence of a second ventral motor knob seems to be unique to humans. Humans and orangutans exhibit the most similar and complex central sulcus shapes. However, their similarities may reflect divergent evolutionary processes related to selection for different positional and habitual locomotor functions.


Asunto(s)
Evolución Biológica , Gorilla gorilla , Hominidae , Imagen por Resonancia Magnética , Corteza Motora , Pan troglodytes , Filogenia , Animales , Humanos , Masculino , Pan troglodytes/anatomía & histología , Pan troglodytes/fisiología , Gorilla gorilla/anatomía & histología , Gorilla gorilla/fisiología , Femenino , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Corteza Motora/diagnóstico por imagen , Hominidae/anatomía & histología , Hominidae/fisiología , Adulto , Mano/fisiología , Mano/anatomía & histología , Adulto Joven , Pongo pygmaeus/anatomía & histología , Pongo pygmaeus/fisiología , Especificidad de la Especie , Pongo abelii/anatomía & histología , Pongo abelii/fisiología
4.
J Infect Dis ; 230(1): 5-14, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052699

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a variety of clinical manifestations, many of which originate from altered immune responses, either locally or systemically. Immune cell cross-talk occurs mainly in lymphoid organs. However, systemic cell interaction specific to coronavirus disease 2019 has not been well characterized. Here, by employing single-cell RNA sequencing and imaging flow cytometry analysis, we unraveled, in peripheral blood, a heterogeneous group of cell complexes formed by the adherence of CD14+ monocytes to different cytotoxic lymphocytes, including SARS-CoV-2-specific CD8+ T cells, γδ T cells, and natural killer T cells. These lymphocytes attached to CD14+ monocytes that showed enhanced inflammasome activation and pyroptosis-induced cell death in progression stage; in contrast, in the convalescent phase, CD14+ monocytes with elevated antigen presentation potential were targeted by cytotoxic lymphocytes, thereby restricting the excessive immune activation. Collectively, our study reports previously unrecognized cell-cell interplay in the SARS-CoV-2-specific immune response, providing new insight into the intricacy of dynamic immune cell interaction representing antiviral defense.


Asunto(s)
COVID-19 , Monocitos , SARS-CoV-2 , Linfocitos T Citotóxicos , Humanos , COVID-19/inmunología , COVID-19/virología , Monocitos/inmunología , SARS-CoV-2/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T CD8-positivos/inmunología , Receptores de Lipopolisacáridos/metabolismo , Inflamasomas/inmunología , Piroptosis/inmunología , Células T Asesinas Naturales/inmunología , Masculino , Comunicación Celular/inmunología , Análisis de la Célula Individual
5.
Neurobiol Dis ; 192: 106428, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38307367

RESUMEN

The heart and brain are the core organs of the circulation and central nervous system, respectively, and play an important role in maintaining normal physiological functions. Early neuronal and cardiac damage affects organ function. The relationship between the heart and brain is being continuously investigated. Evidence-based medicine has revealed the concept of the "heart- brain axis," which may provide new therapeutic strategies for certain diseases. Takeda protein-coupled receptor 5 (TGR5) is a metabolic regulator involved in energy homeostasis, bile acid homeostasis, and glucose and lipid metabolism. Inflammation is critical for the development and regeneration of the heart and brain during metabolic diseases. Herein, we discuss the role of TGR5 as a metabolic regulator of heart and brain development and injury to facilitate new therapeutic strategies for metabolic and ischemic diseases of the heart and brain.


Asunto(s)
Lesiones Encefálicas , Enfermedades Metabólicas , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Inflamación/metabolismo
6.
Int J Cancer ; 154(11): 1948-1954, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38323658

RESUMEN

Endometriosis has been reported in epidemiological studies to be associated with certain types of cancer. However, the presence of reverse causality and residual confounding due to common risk factors introduces uncertainty regarding the extent to which endometriosis itself contributes to the development of cancer. We performed the Mendelian randomization (MR) to investigate the causal associations between endometriosis and 34 different types of cancers. The results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for ovarian cancer (OR = 3.2913; p-value = .0320). The genetic liabilities to endometriosis had causal associations with the decreased risk for skin cancer (OR = 0.9973; p-value = .0219), hematological cancer (OR = 0.9953; p-value = .0175) and ER- breast cancer (OR = 0.6960; p-value = .0381). The causal association of the above combinations were robust by test of heterogeneity and pleiotropy. Together, our study suggests that endometriosis had causal effect on cancer risk.


Asunto(s)
Neoplasias de la Mama , Endometriosis , Femenino , Humanos , Endometriosis/complicaciones , Endometriosis/epidemiología , Endometriosis/genética , Análisis de la Aleatorización Mendeliana , Causalidad , Factores de Riesgo , Neoplasias de la Mama/etiología , Neoplasias de la Mama/genética , Estudio de Asociación del Genoma Completo
7.
BMC Plant Biol ; 24(1): 143, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38413873

RESUMEN

BACKGROUND: Solar radiation is primarily composed of ultraviolet radiation (UVR, 200 - 400 nm) and photosynthetically active radiation (PAR, 400 - 700 nm). Ultraviolet-B (UVB) radiation accounts for only a small proportion of sunlight, and it is the primary cause of plant photodamage. The use of chlorofluorocarbons (CFCs) as refrigerants caused serious ozone depletion in the 1980s, and this had led to an increase in UVB. Although CFC emissions have significantly decreased in recent years, UVB radiation still remains at a high intensity. UVB radiation increase is an important factor that influences plant physiological processes. Ulva prolifera, a type of macroalga found in the intertidal zone, is intermittently exposed to UVB. Alternative oxidase (AOX) plays an important role in plants under stresses. This research examines the changes in AOX activity and the relationships among AOX, photosynthesis, and reactive oxygen species (ROS) homeostasis in U. prolifera under changes in UVB and photosynthetically active radiation (PAR). RESULTS: UVB was the main component of solar radiation impacting the typical intertidal green macroalgae U. prolifera. AOX was found to be important during the process of photosynthesis optimization of U. prolifera due to a synergistic effect with non-photochemical quenching (NPQ) under UVB radiation. AOX and glycolate oxidase (GO) worked together to achieve NADPH homeostasis to achieve photosynthesis optimization under changes in PAR + UVB. The synergism of AOX with superoxide dismutase (SOD) and catalase (CAT) was important during the process of ROS homeostasis under PAR + UVB. CONCLUSIONS: AOX plays an important role in the process of photosynthesis optimization and ROS homeostasis in U. prolifera under UVB radiation. This study provides further insights into the response of intertidal macroalgae to solar light changes.


Asunto(s)
Algas Comestibles , Proteínas Mitocondriales , Oxidorreductasas , Proteínas de Plantas , Algas Marinas , Rayos Ultravioleta , Ulva , Especies Reactivas de Oxígeno , Fotosíntesis/fisiología , Aclimatación
8.
BMC Plant Biol ; 24(1): 729, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080585

RESUMEN

BACKGROUND: Straw incorporation serves as an effective strategy to enhance soil fertility and soil microbial biomass carbon (SMBC), which in turn improves maize yield and agricultural sustainability. However, our understanding of nitrogen (N) fertilization and straw incorporation into soil microenvironment is still evolving. This study explored the impact of six N fertilization rates (N0, N100, N150, N200, N250, and N300) with and without straw incorporation on soil fertility, SMBC, enzyme activities, and maize yield. RESULTS: Results showed that both straw management and N fertilization significantly affected soil organic carbon (SOC), total N, SMBC, soil enzyme activities, and maize yield. Specifically, the N250 treatment combined with straw incorporation significantly increased SOC, total N, and SMBC compared to lower fertilization rates. Additionally, enzyme activities such as urease, cellulase, sucrose, catalase, and acid phosphatase reached their peak during the V6 growth stage in the N200 treatment under for both straw management conditions. Compared to N250 and N300 treatments of traditional planting, the N200 treatment with residue incorporation significantly increased yield by 8.30 and 4.22%, respectively. All measured parameters, except for cellulase activity, were significantly higher in spring than in the autumn across both study years, with notable increases observed in 2021. CONCLUSIONS: These findings suggest that optimal levels of SOC, soil total N (STN), and SMBC, along with increased soil enzyme activities, is crucial for sustaining soil fertility and enhancing maize grain yield under straw incorporation and N200 treatments.


Asunto(s)
Fertilizantes , Nitrógeno , Suelo , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Suelo/química , Nitrógeno/metabolismo , Producción de Cultivos/métodos , Carbono/metabolismo , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Biomasa , Microbiología del Suelo , Agricultura/métodos
9.
Small ; 20(29): e2310868, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38368273

RESUMEN

Inverted flexible perovskite solar cells (fPSCs) are promising for commercialization due to their low cost, lightweight, and excellent stability. However, enhancing fPSCs' power conversion efficiency and stability remains challenging. Here, an unprecedented triple cross-linking engineering strategy is innovatively exhibit for efficient and stable inverted fPSCs. First, a carefully designed cross-linker, 4-fluorophenyl 5-(1,2-dithiolan-3-yl) pentanoate (FB-TA), is added to the perovskite precursor solution. During the perovskite film's crystallization at a low temperature, the cross-linking product of FB-TA can passivate the grain boundaries and reduce the film's residual strain and Young's module. Then, FB-TA is also introduced for the bottom- and top-interface modification of the perovskite film. The interfacial treating strategy protects the perovskite from water invasion and strengthens the interfaces. The combination of triple strategies affords highly efficient inverted fPSCs with a champion efficiency of 21.42% among the state-of-the-art inverted fPSCs based on nickel oxides. More importantly, the flexible devices also exhibit superior stabilities with T90 >4000 bending cycles, photostability with T90 >568 h, and ambient stability with T90 >2000 h, especially the stability with T80 >1120 h under harsh damp-heat conditions (i.e., 85 °C and 85% RH). The strategy provides new insights into the industrialization of high-performance and stable fPSCs.

10.
Small ; : e2402402, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949051

RESUMEN

Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.

11.
Reproduction ; 168(3)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38941177

RESUMEN

In brief: The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas. Abstract: There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.


Asunto(s)
Aminoácidos , Biomarcadores , Metabolómica , Resultado del Embarazo , Ursidae , Femenino , Embarazo , Animales , Ursidae/sangre , Ursidae/fisiología , Aminoácidos/sangre , Aminoácidos/metabolismo , Biomarcadores/sangre , Preñez/sangre , Preñez/metabolismo , Arginina/sangre , Arginina/metabolismo , Metaboloma , Histidina/sangre , Histidina/metabolismo
12.
Phys Rev Lett ; 132(13): 138401, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38613297

RESUMEN

Chirality is an essential nature of biological systems. However, it remains obscure how the handedness at the microscale is translated into chiral morphogenesis at the tissue level. Here, we investigate three-dimensional (3D) tissue morphogenesis using an active fluid theory invoking chirality. We show that the coordination of achiral and chiral stresses, arising from microscopic interactions and energy input of individual cells, can engender the self-organization of 3D papillary and helical structures. The achiral active stress drives the nucleation of asterlike topological defects, which initiate 3D out-of-plane budding, followed by rodlike elongation. The chiral active stress excites vortexlike topological defects, which favor the tip spheroidization and twisting of the elongated rod. These results unravel the chiral morphogenesis observed in our experiments of 3D organoids generated by human embryonic stem cells.


Asunto(s)
División Celular , Humanos , Morfogénesis
13.
Eur J Nucl Med Mol Imaging ; 51(6): 1530-1543, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38189910

RESUMEN

PURPOSE: Noninvasive quantifying activated hepatic stellate cells (aHSCs) by molecular imaging is helpful for assessing disease progression and therapeutic responses of liver fibrosis. Our purpose is to develop platelet-derived growth factor receptor ß (PDGFRß)-targeted radioactive tracer for assessing liver fibrosis by positron emission tomography (PET) imaging of aHSCs. METHODS: Comparative transcriptomics, immunofluorescence staining and flow cytometry were used to evaluate PDGFRß as biomarker for human aHSCs and determine the correlation of PDGFRß with the severity of liver fibrosis. The high affinity affibody for PDGFRß (ZPDGFRß) was labeled with gallium-68 (68Ga) for PET imaging of mice with carbon tetrachloride (CCl4)-induced liver fibrosis. Binding of the [68Ga]Ga-labeled ZPDGFRß ([68Ga]Ga-DOTA-ZPDGFRß) for aHSCs in human liver tissues was measured by autoradiography. RESULTS: PDGFRß overexpressed in aHSCs was highly correlated with the severity of liver fibrosis in patients and CCl4-treated mice. The 68Ga-labeled ZPDGFRß affibody ([68Ga]Ga-DOTA-ZPDGFRß) showed PDGFRß-dependent binding to aHSCs. According to the PET imaging, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß increased with the accumulation of aHSCs and collagens in the fibrotic livers of mice. In contrast, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß decreased with spontaneous recovery or treatment of liver fibrosis, indicating that the progression and therapeutic responses of liver fibrosis in mice could be visualized by PDGFRß-targeted PET imaging. [68Ga]Ga-DOTA-ZPDGFRß also bound human aHSCs and visualized fibrosis in patient-derived liver tissues. CONCLUSIONS: PDGFRß is a reliable biomarker for both human and mouse aHSCs. PDGFRß-targeted PET imaging could be used for noninvasive monitoring of liver fibrosis in mice and has great potential for clinical translation.


Asunto(s)
Radioisótopos de Galio , Cirrosis Hepática , Tomografía de Emisión de Positrones , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/metabolismo , Animales , Tomografía de Emisión de Positrones/métodos , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratones , Masculino , Células Estrelladas Hepáticas/metabolismo , Compuestos Heterocíclicos con 1 Anillo/química
14.
Chemistry ; 30(35): e202401150, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38639722

RESUMEN

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state.

15.
BMC Cancer ; 24(1): 418, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580939

RESUMEN

BACKGROUND: This study aimed to develop and validate a machine learning (ML)-based fusion model to preoperatively predict Ki-67 expression levels in patients with head and neck squamous cell carcinoma (HNSCC) using multiparametric magnetic resonance imaging (MRI). METHODS: A total of 351 patients with pathologically proven HNSCC from two medical centers were retrospectively enrolled in the study and divided into training (n = 196), internal validation (n = 84), and external validation (n = 71) cohorts. Radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images and screened. Seven ML classifiers, including k-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forest (RF), linear discriminant analysis (LDA), naive Bayes (NB), and eXtreme Gradient Boosting (XGBoost) were trained. The best classifier was used to calculate radiomics (Rad)-scores and combine clinical factors to construct a fusion model. Performance was evaluated based on calibration, discrimination, reclassification, and clinical utility. RESULTS: Thirteen features combining multiparametric MRI were finally selected. The SVM classifier showed the best performance, with the highest average area under the curve (AUC) of 0.851 in the validation cohorts. The fusion model incorporating SVM-based Rad-scores with clinical T stage and MR-reported lymph node status achieved encouraging predictive performance in the training (AUC = 0.916), internal validation (AUC = 0.903), and external validation (AUC = 0.885) cohorts. Furthermore, the fusion model showed better clinical benefit and higher classification accuracy than the clinical model. CONCLUSIONS: The ML-based fusion model based on multiparametric MRI exhibited promise for predicting Ki-67 expression levels in HNSCC patients, which might be helpful for prognosis evaluation and clinical decision-making.


Asunto(s)
Neoplasias de Cabeza y Cuello , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Teorema de Bayes , Antígeno Ki-67/genética , Radiómica , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Aprendizaje Automático , Neoplasias de Cabeza y Cuello/diagnóstico por imagen
16.
Muscle Nerve ; 70(1): 60-70, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38482981

RESUMEN

INTRODUCTION/AIMS: Eteplirsen, approved in the US for patients with Duchenne muscular dystrophy (DMD) with exon 51 skip-amenable variants, is associated with attenuated ambulatory/pulmonary decline versus DMD natural history (NH). We report overall survival in a US cohort receiving eteplirsen and contextualize these outcomes versus DMD NH. METHODS: US patients with DMD receiving eteplirsen were followed through a patient support program, with data collected on ages at eteplirsen initiation and death/end of follow-up. Individual DMD NH data were extracted by digitizing Kaplan-Meier (KM) curves from published systematic and targeted literature reviews. Overall survival age was analyzed using KM curves and contextualized with DMD NH survival curves; subanalyses considered age groups and duration of eteplirsen exposure. Overall survival time from treatment initiation was also evaluated. RESULTS: A total of 579 eteplirsen-treated patients were included. During a total follow-up of 2119 person-years, median survival age was 32.8 years. DMD NH survival curves extracted from four publications (follow-up for 1224 DMD NH controls) showed overall pooled median survival age of 27.4 years. Eteplirsen-treated patients had significantly longer survival from treatment initiation versus age-matched controls (age-adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.98; p < .05). Longer treatment exposure was associated with improved survival (HR, 0.15; 95% CI, 0.05-0.41; p < .001). Comparisons using different DMD NH cohorts to address common risks of bias yielded consistent findings. DISCUSSION: Data suggest eteplirsen may prolong survival in patients with DMD across a wide age range. As more data become available, the impact of eteplirsen on survival will be further elucidated.


Asunto(s)
Distrofia Muscular de Duchenne , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/mortalidad , Humanos , Masculino , Niño , Adolescente , Adulto , Preescolar , Adulto Joven , Morfolinos/uso terapéutico , Femenino , Estudios de Cohortes , Estudios de Seguimiento , Estimación de Kaplan-Meier
17.
Pediatr Res ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745029

RESUMEN

BACKGROUND: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial. METHODS: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed. RESULTS: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI. CONCLUSIONS: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor. IMPACT: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators.

18.
J Org Chem ; 89(4): 2588-2598, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38270667

RESUMEN

An efficient O-H insertion of hydrogenphosphate derivatives and α-diazo compounds has been developed to construct α-phosphoryloxy scaffolds. Diverse α-phosphoryloxy skeletons could be obtained under mild and catalyst-free conditions in good yields. The control experiments suggest a protonation and nucleophilic addition process of α-diazo compounds via a diazonium ion pair for this transformation.

19.
Phys Chem Chem Phys ; 26(32): 21677-21687, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39091182

RESUMEN

In recent years, great progress has been made on the study of nanozymes with enzyme-like properties. Here, bimetallic Fe and Ni nanoclusters were anchored on the nanosheets of nitrogen-rich layered graphitic carbon nitride by one-step pyrolysis at high temperature (Fe/Ni-CN). The loading content of Fe and Ni on Fe/Ni-CN is as high as 8.0%, and Fe/Ni-CN has a high specific surface area of 121.86 m2 g-1. The Fe/Ni-CN can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and exhibits efficient peroxidase-like activity, leading to a 17.2-fold increase compared to pure graphitic carbon nitride (CN). Similar to the natural horseradish peroxidase (HRP), the Fe/Ni-CN nanozyme follows catalytic kinetics. The Michaelis-Menten constant (Km) value of the Fe/Ni-CN nanozyme for TMB is about 8.3-fold lower than that for HRP, which means that the Fe/Ni-CN nanozyme has better affinity for TMB. In addition, the catalytic mechanism was investigated by combination of free radical quenching experiments and density-functional theory (DFT) calculations. The results show that the high peroxidase-like activity is due to the easy adsorption of H2O2 after bimetal loading, which is conducive to the production of hydroxyl radicals. Based on the extraordinary peroxidase-like activity, the colorimetric detection of p-phenylenediamine (PPD) was constructed with a wide linear range of 0.2-30 µM and a low detection limit of 0.02 µM. The sensor system has been successfully applied to the detection of residual PPD in real dyed hair samples. The results show that the colorimetric method is sensitive, highly selective and accurate. This study provides a new idea for the efficient enhancement of nanozyme activity and effective detection of PPD by a bimetallic synergistic strategy.


Asunto(s)
Colorimetría , Grafito , Hierro , Níquel , Compuestos de Nitrógeno , Fenilendiaminas , Grafito/química , Fenilendiaminas/química , Colorimetría/métodos , Compuestos de Nitrógeno/química , Níquel/química , Hierro/química , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Nitrilos/química , Límite de Detección , Catálisis , Bencidinas/química
20.
BMC Cardiovasc Disord ; 24(1): 189, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561664

RESUMEN

BACKGROUND: The Systemic Immune-Inflammation Index (SII), a novel marker of inflammation based on neutrophil, platelet, and lymphocyte counts, has demonstrated potential prognostic value in patients undergoing percutaneous coronary intervention (PCI). Our aim was to assess the correlation between the SII and major adverse cardiovascular events following percutaneous coronary intervention. METHODS: We searched PubMed, Web of Science, Embase, and The Cochrane Library from inception to November 20, 2023, for cohort studies investigating the association between SII and the occurrence of MACEs after PCI. Statistical analysis was performed using Revman 5.3, with risk ratios (RRs) and 95% confidence intervals (CIs) as relevant parameters. RESULTS: In our analysis, we incorporated a total of 8 studies involving 11,117 participants. Our findings revealed that a high SII is independently linked to a increased risk of MACEs in PCI patients (RR: 2.08,95%CI: 1.87-2.32, I2 = 42%, p < 0.00001). Additionally, we demonstrated the prognostic value of SII in all-cause mortality, heart failure, and non-fatal myocardial infarction. CONCLUSIONS: Elevated SII may serve as a potential predictor for subsequent occurrence of MACEs in patients undergoing PCI. TRIAL REGISTRATION: Our protocol was registered in PROSPERO (registration number: CRD42024499676).


Asunto(s)
Inflamación , Neutrófilos , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Medición de Riesgo , Factores de Riesgo , Femenino , Masculino , Inflamación/inmunología , Inflamación/sangre , Inflamación/diagnóstico , Persona de Mediana Edad , Recuento de Linfocitos , Anciano , Resultado del Tratamiento , Neutrófilos/inmunología , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/sangre , Recuento de Plaquetas
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