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Various forms of ecological monitoring and disease diagnosis rely upon the detection of amphiphiles, including lipids, lipopolysaccharides, and lipoproteins, at ultralow concentrations in small droplets. Although assays based on droplets' wettability provide promising options in some cases, their reliance on the measurements of surface and bulk properties of whole droplets (e.g., contact angles, surface tensions) makes it difficult to monitor trace amounts of these amphiphiles within small-volume samples. Here, we report a design principle in which self-assembled monolayer-functionalized microstructured surfaces coated with silicone oil create locally disordered regions within a droplet's contact lines to effectively concentrate amphiphiles within the areas that dominate the droplet static friction. Remarkably, such surfaces enable the ultrasensitive, naked-eye detection of amphiphiles through changes in the droplets' sliding angles, even when the concentration is four to five orders of magnitude below their critical micelle concentration. We develop a thermodynamic model to explain the partitioning of amphiphiles at the contact line by their cooperative association within the disordered, loosely packed regions of the self-assembled monolayer. Based on this local analyte concentrating effect, we showcase laboratory-on-a-chip surfaces with positionally dependent pinning forces capable of both detecting industrially and biologically relevant amphiphiles (e.g., bacterial endotoxins), as well as sorting aqueous droplets into discrete groups based on their amphiphile concentrations. Furthermore, we demonstrate that the sliding behavior of amphiphile-laden aqueous droplets provides insight into the amphiphile's effective length, thereby allowing these surfaces to discriminate between analytes with highly disparate molecular sizes.
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Micelas , Aceites de Silicona , Lipopolisacáridos , Tensión Superficial , Agua , HumectabilidadRESUMEN
Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.
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Neoplasias Encefálicas , Humanos , Bevacizumab/efectos adversos , Estudios Retrospectivos , Necrosis/etiología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologíaRESUMEN
Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Humanos , Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno B7-H1 , Receptor de Muerte Celular Programada 1 , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Nasofaríngeo , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Linfocitos T/patologíaRESUMEN
Aqueous zinc-ion batteries (AZIBs) are considered a promising device for next-generation energy storage due to their high safety and low cost. However, developing high-performance cathodes that can be matched with zinc metal anodes remains a challenge in unlocking the full potential of AZIBs. In this study, a typical transition metal layered double hydroxides (NiCo-LDHs) can be in situ reconstructed to NiCo-LDHs/Ni(Co)OOH heterostructure using an electrochemical cycling activation (ECA) method, serving as a novel cathode material for AZIBs. The optimized ECA-NiCo-LDHs cathode demonstrates a high capacity of 181.5 mAh g-1 at 1 A g-1 and retains 75% of initial capacity after 700 cycles at 5 A g-1. The abundant heterointerfaces of the NiCo-LDHs/Ni(Co)OOH material can activate additional active sites for zinc-ion storage and accelerate ion diffusion. Theoretical calculations also suggest the heterostructure can boost charge transfer and regulate ion-adsorption capability, thereby improving the electrochemical performance. Additionally, the flexible AZIBs device exhibits good service performance. This study on interface engineering introduces a new possibility for utilizing LDHs in AZIBs and offers a novel strategy for designing electrode materials.
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The primary mechanisms contributing to nitrogen (N) addition induced grassland biodiversity loss, namely light competition and soil cation toxicity, are often examined separately in various studies. However, their relative significance in governing biodiversity loss along N addition gradient remains unclear. We conducted a 4-yr field experiment with five N addition rates (0, 2, 10, 20, and 50 g N m-2 yr-1) and performed a meta-analysis using global data from 239 observations in N-fertilized grassland ecosystems. Results from our field experiment and meta-analysis indicate that both light competition and soil cation (e.g. Mn2+ and Al3+) toxicity contribute to plant diversity loss under N enrichment. The relative importance of these mechanisms varied with N enrichment intensity. Light competition played a more significant role in influencing species richness under low N addition (≤ 10 g m-2 yr-1), while cation toxicity became increasingly dominant in reducing biodiversity under high N addition (>10 g m-2 yr-1). Therefore, a transition from light competition to cation toxicity occurs with increasing N availability. These findings imply that the biodiversity loss along the N gradient is regulated by distinct mechanisms, necessitating the adoption of differential management strategies to mitigate diversity loss under varying intensities of N enrichment.
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Biodiversidad , Cationes , Luz , Nitrógeno , Nitrógeno/metabolismo , Cationes/metabolismo , Suelo/química , Pradera , Plantas/metabolismo , Plantas/efectos de la radiación , Plantas/efectos de los fármacosRESUMEN
The fixation and transfer of biological nitrogen from peanuts to maize in maize-peanut intercropping systems play a pivotal role in maintaining the soil nutrient balance. However, the mechanisms through which root interactions regulate biological nitrogen fixation and transfer remain unclear. This study employed a 15N isotope labelling method to quantify nitrogen fixation and transfer from peanuts to maize, concurrently elucidating key microorganisms and genera in the nitrogen cycle through metagenomic sequencing. The results revealed that biological nitrogen fixation in peanut was 50 mg and transfer to maize was 230 mg when the roots interacted. Moreover, root interactions significantly increased nitrogen content and the activities of protease, dehydrogenase (DHO) and nitrate reductase in the rhizosphere soil. Metagenomic analyses and structural equation modelling indicated that nrfC and nirA genes played important roles in regulating nitrogen fixation and transfer. Bradyrhizobium was affected by soil nitrogen content and DHO, indirectly influencing the efficiency of nitrogen fixation and transfer. Overall, our study identified key bacterial genera and genes associated with nitrogen fixation and transfer, thus advancing our understanding of interspecific interactions and highlighting the pivotal role of soil microorganisms and functional genes in maintaining soil ecosystem stability from a molecular ecological perspective.
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BACKGROUND: Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. METHOD: Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. RESULT: We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. CONCLUSION: This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming.
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Angiopatías Diabéticas , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , Análisis de la Célula Individual , Transcriptoma , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/patología , Angiopatías Diabéticas/fisiopatología , Masculino , Redes Reguladoras de Genes , Metabolómica , Perfilación de la Expresión Génica , Persona de Mediana Edad , Reprogramación Celular , Anciano , Femenino , Metaboloma , Calcificación Vascular/metabolismo , Calcificación Vascular/genética , Calcificación Vascular/patología , Metabolismo Energético/genética , Regulación de la Expresión Génica , Reprogramación Metabólica , MultiómicaRESUMEN
BACKGROUND: The expression level of apolipoprotein E (APOE) in pancreatic ductal adenocarcinoma (PDAC) and its effect on the prognosis of PDAC patients are not clear. The effect of APOE on the immune status of patients with PDAC has not been elucidated. METHODS: We obtained pancreatic cancer data from the TCGA and GETx databases. Patients with PDAC who underwent pancreatic surgery at the Second Affiliated Hospital of Jiaxing University between 2012 and 2021 were included. Clinical pathological data were recorded, plasma APOE levels were measured, and tissue samples were collected. A tissue microarray was generated using the collected tissue samples. APOE and CD4 staining was performed to determine immunoreactive scores (IRSs). The expression of APOE in the plasma and tumour tissues of pancreatic cancer patients was analysed and compared. The correlations between plasma APOE levels, tissue APOE levels and clinicopathological characteristics were analysed. Survival prognosis was analysed using Kaplan-Meier survival analysis and Cox multivariate regression analysis. The correlations between APOE expression levels and immune biomarkers and immune cells were further analysed. Single-cell analysis of APOE distribution in various cells was performed on the TISCH website. RESULTS: APOE was highly expressed in the tumour tissue of pancreatic cancer patients, and high plasma APOE levels were associated with poor prognosis. Females, patients with high-grade disease and patients with pancreatic head carcinoma had high plasma APOE levels. High APOE expression in tumour tissues was associated with good prognosis. Mononuclear macrophages in the pancreatic cancer microenvironment primarily expressed APOE. APOE levels positively correlated with immune biomarkers, such as CD8A, PDCD1, GZMA, CXCL10, and CXCL9, in the tumour microenvironment. APOE promoted CD4 + T cell or dendritic cell infiltration in the tumour microenvironment. CONCLUSIONS: APOE may affect the occurrence and development of pancreatic cancer by regulating the infiltration of immune cells in the tumour microenvironment.
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Apolipoproteínas E , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/sangre , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/sangre , Pronóstico , Microambiente Tumoral/inmunologíaRESUMEN
It is becoming increasingly common for researchers to consider leveraging information from external sources to enhance the analysis of small-scale studies. While much attention has focused on univariate survival data, correlated survival data are prevalent in epidemiological investigations. In this article, we propose a unified framework to improve the estimation of the marginal accelerated failure time model with correlated survival data by integrating additional information given in the form of covariate effects evaluated in a reduced accelerated failure time model. Such auxiliary information can be summarized by using valid estimating equations and hence can then be combined with the internal linear rank-estimating equations via the generalized method of moments. We investigate the asymptotic properties of the proposed estimator and show that it is more efficient than the conventional estimator using internal data only. When population heterogeneity exists, we revise the proposed estimation procedure and present a shrinkage estimator to protect against bias and loss of efficiency. Moreover, the proposed estimation procedure can be further refined to accommodate the non-negligible uncertainty in the auxiliary information, leading to more trustable inference conclusions. Simulation results demonstrate the finite sample performance of the proposed methods, and empirical application on the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial substantiates its practical relevance.
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The analysis of streaming time-to-event cohorts has garnered significant research attention. Most existing methods require observed cohorts from a study sequence to be independent and identically sampled from a common model. This assumption may be easily violated in practice. Our methodology operates within the framework of online data updating, where risk estimates for each cohort of interest are continuously refreshed using the latest observations and historical summary statistics. At each streaming stage, we introduce parameters to quantify the potential discrepancy between batch-specific effects from adjacent cohorts. We then employ penalized estimation techniques to identify nonzero discrepancy parameters, allowing us to adaptively adjust risk estimates based on current data and historical trends. We illustrate our proposed method through extensive empirical simulations and a lung cancer data analysis.
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Simulación por Computador , Neoplasias Pulmonares , Humanos , Medición de Riesgo/métodos , Estudios de Cohortes , Modelos Estadísticos , Factores de TiempoRESUMEN
BACKGROUND: Many existing healthcare ranking systems are notably intricate. The standards for peer review and evaluation often differ across specialties, leading to contradictory results among various ranking systems. There is a significant need for a comprehensible and consistent mode of specialty assessment. METHODS: This quantitative study aimed to assess the influence of clinical specialties on the regional distribution of patient origins based on 10,097,795 outpatient records of a large comprehensive hospital in South China. We proposed the patient regional index (PRI), a novel metric to quantify the regional influence of hospital specialties, using the principle of representative points of a statistical distribution. Additionally, a two-dimensional measure was constructed to gauge the significance of hospital specialties by integrating the PRI and outpatient volume. RESULTS: We calculated the PRI for each of the 16 specialties of interest over eight consecutive years. The longitudinal changes in the PRI accurately captured the impact of the 2017 Chinese healthcare reforms and the 2020 COVID-19 pandemic on hospital specialties. At last, the two-dimensional assessment model we devised effectively illustrates the distinct characteristics across hospital specialties. CONCLUSION: We propose a novel, straightforward, and interpretable index for quantifying the influence of hospital specialties. This index, built on outpatient data, requires only the patients' origin, thereby facilitating its widespread adoption and comparison across specialties of varying backgrounds. This data-driven method offers a patient-centric view of specialty influence, diverging from the traditional reliance on expert opinions. As such, it serves as a valuable augmentation to existing ranking systems.
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Macrodatos , COVID-19 , Humanos , China , COVID-19/epidemiología , SARS-CoV-2 , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Instituciones de Atención Ambulatoria/normas , Pandemias , Medicina/estadística & datos numéricos , Especialización/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Reforma de la Atención de SaludRESUMEN
Gastric cancer (GC) is a major contributor to cancer-related deaths and is characterized by high heterogeneity in epidemiology and histopathology worldwide. Increasing evidence indicates that circular RNAs (circRNAs) play multifaceted roles in cellular processes in human cancers. Here, we demonstrated that circFNTA high expression increases the proliferation, metastasis, and epithelial-mesenchymal transition process and tumorigenicity of GC cells. First, we found that circFNTA was upregulated in GC cells and tissues, and the high circFNTA levels were positively associated with the poor prognosis in GC patients. Using luciferase reporter and RNA-pull down assays, we elucidated that circFNTA sponged two microRNAs, miR-604 and miR-647. In addition, the proliferation and metastatic ability of GC cell reduction caused by silencing circFNTA was hindered by inhibitors of miR-604 and miR-647. Moreover, SCN8A was predicted by miRDB as a common target gene of miR-604 and miR-647, which was then verified by the luciferase reporter assay. Knockdown of circFNTA causes messenger RNA and protein levels in SCN8A to be downregulated in GC cells. However, this effect was overturned by cotransfection miR-604 and miR-647. Also, we identified that SCN8A was downregulated in GC tissues, which was positively correlated with circFNTA expression. In rescue experiments, the attenuated cell proliferation and metastatic ability caused by circFNTA knockdown was reversed by miR-604 and miR-647 inhibitors and SCN8A overexpression. Collectively, our findings suggest an oncogenic role of circFNTA in GC progression and elucidate that circFNTA exerts its function by modulating the miR-604/miR-647/SCN8A axis.
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MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Carcinogénesis/genética , Transformación Celular Neoplásica , Luciferasas/genética , Luciferasas/metabolismo , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Canal de Sodio Activado por Voltaje NAV1.6/genética , Canal de Sodio Activado por Voltaje NAV1.6/metabolismoRESUMEN
Liquid crystals (LCs) are anisotropic fluids that combine the long-range order of crystals with the mobility of liquids1,2. This combination of properties has been widely used to create reconfigurable materials that optically report information about their environment, such as changes in electric fields (smart-phone displays) 3 , temperature (thermometers) 4 or mechanical shear 5 , and the arrival of chemical and biological stimuli (sensors)6,7. An unmet need exists, however, for responsive materials that not only report their environment but also transform it through self-regulated chemical interactions. Here we show that a range of stimuli can trigger pulsatile (transient) or continuous release of microcargo (aqueous microdroplets or solid microparticles and their chemical contents) that is trapped initially within LCs. The resulting LC materials self-report and self-regulate their chemical response to targeted physical, chemical and biological events in ways that can be preprogrammed through an interplay of elastic, electrical double-layer, buoyant and shear forces in diverse geometries (such as wells, films and emulsion droplets). These LC materials can carry out complex functions that go beyond the capabilities of conventional materials used for controlled microcargo release, such as optically reporting a stimulus (for example, mechanical shear stresses generated by motile bacteria) and then responding in a self-regulated manner via a feedback loop (for example, to release the minimum amount of biocidal agent required to cause bacterial cell death).
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Cristales Líquidos/química , Liberación de Fármacos/efectos de la radiación , Elasticidad , Electricidad , Escherichia coli/fisiología , Dedos/fisiología , Calor , Humanos , Luz , Cristales Líquidos/efectos de la radiación , TactoRESUMEN
Abiotic CO2 reduction on transition metal minerals has been proposed to account for the synthesis of organic compounds in alkaline hydrothermal systems, but this reaction lacks experimental support, as only short-chain hydrocarbons (
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AIM: Lambl's excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl's excrescences are associated with migraine. METHODS: Retrospective review of 182 inpatients with Lambl's excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl's excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits. RESULTS: A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl's excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl's excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications. CONCLUSIONS: This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache. And intervention for Lambl's excrescences may be crucial for preventing headache recurrence.
This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations.
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Auxin plays a crucial role in regulating root growth and development, and its distribution pattern under environmental stimuli significantly influences root plasticity. Under K deficiency, the interaction between K+ transporters and auxin can modulate root development. This study compared the differences in root morphology and physiological mechanisms of the low-K-tolerant maize inbred line 90-21-3 and K-sensitive maize inbred line D937 under K-deficiency (K+ = 0.2 mM) with exogenous NAA (1-naphthaleneacetic acid, NAA = 0.01 mM) treatment. Root systems of 90-21-3 exhibited higher K+ absorption efficiency. Conversely, D937 seedling roots demonstrated greater plasticity and higher K+ content. In-depth analysis through transcriptomics and metabolomics revealed that 90-21-3 and D937 seedling roots showed differential responses to exogenous NAA under K-deficiency. In 90-21-3, upregulation of the expression of K+ absorption and transport-related proteins (proton-exporting ATPase and potassium transporter) and the enrichment of antioxidant-related functional genes were observed. In D937, exogenous NAA promoted the responses of genes related to intercellular ethylene and cation transport to K-deficiency. Differential metabolite enrichment analysis primarily revealed significant enrichment in flavonoid biosynthesis, tryptophan metabolism, and hormone signaling pathways. Integrated transcriptomic and metabolomic analyses revealed that phenylpropanoid biosynthesis is a crucial pathway, with core genes (related to peroxidase enzyme) and core metabolites upregulated in 90-21-3. The findings suggest that under K-deficiency, exogenous NAA induces substantial changes in maize roots, with the phenylpropanoid biosynthesis pathway playing a crucial role in the maize root's response to exogenous NAA regulation under K-deficiency.
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Deficiencia de Potasio , Plantones , Plantones/genética , Plantones/metabolismo , Zea mays/metabolismo , Deficiencia de Potasio/metabolismo , Transcriptoma , Perfilación de la Expresión Génica , Ácidos Indolacéticos/farmacología , Ácidos Indolacéticos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.
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Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Biomarcadores de Tumor , Neoplasias PancreáticasRESUMEN
Bismuth (Bi) has attracted attention as a promising anode for sodium-ion batteries (SIBs) owing to its suitable potential and high theoretical capacity. However, the large volumetric changes during cycling leads to severe degradation of electrochemical performance and limits its practical application. Herein, Bi nanoflowers are encapsulated in N-doped carbon frameworks to construct a novel Bi@NC composite via a facile solvothermal method and carbonization strategy. The well-designed composite structure endows the Bi@NC with uniformly dispersed Bi nanoflowers to alleviate the attenuation while the N-doped carbon frameworks improve the conductivity and ion transport of the whole electrode. As for sodium-ion half-cell, the electrode exhibits a high specific capacity (384.8 mAh g-1 at 0.1 A g-1 ) and excellent rate performance (341.5 mAh g-1 at 10 A g-1 ), and the capacity retention rate still remains at 94.9% after 5000 cycles at 10 A g-1 . Furthermore, the assembled full-cell with Na3 V2 (PO4 )3 cathode and Bi@NC anode can deliver a high capacity of 251.5 mAh g-1 at 0.1 A g-1 , and its capacity attenuates only 0.009% in each cycle after 2000 times at 5.0 A g-1 . This work offers a convenient, low-cost, and eco-friendliness approach for high-performance electrodes in the field of sodium ion electrochemical storage technology.
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Considering non-Hermitian systems implemented by utilizing enlarged quantum systems, we determine the fundamental limits for the sensitivity of non-Hermitian sensors from the perspective of quantum information. We prove that non-Hermitian sensors do not outperform their Hermitian counterparts (directly couple to the parameter) in the performance of sensitivity, due to the invariance of the quantum information about the parameter. By scrutinizing two concrete non-Hermitian sensing proposals, which are implemented using full quantum systems, we demonstrate that the sensitivity of these sensors is in agreement with our predictions. Our theory offers a comprehensive and model-independent framework for understanding the fundamental limits of non-Hermitian quantum sensors and builds the bridge over the gap between non-Hermitian physics and quantum metrology.
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Partly interval-censored event time data arise naturally in medical, biological, sociological and demographic studies. In practice, some patients may be immune from the event of interest, invoking a cure model for survival analysis. Choosing an appropriate parametric distribution for the failure time of susceptible patients is an important step to fully structure the mixture cure model. In the literature, goodness-of-fit tests for survival models are usually restricted to uncensored or right-censored data. We fill in this gap by proposing a new goodness-of-fit test dealing with partly interval-censored data under mixture cure models. Specifically, we investigate whether a parametric distribution can fit the susceptible part by using a Cramér-von Mises type of test, and establish the asymptotic distribution of the test . Empirically, the critical value is determined from the bootstrap resamples. The proposed test, compared to the traditional leveraged bootstrap approach, yields superior practical results under various settings in extensive simulation studies. Two clinical data sets are analyzed to illustrate our method.