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PURPOSE: In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. METHODS: Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. RESULTS: Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2- to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2- (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). CONCLUSION: Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.
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Biomarcadores de Tumor , Neoplasias de la Mama , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Anciano , Adulto , Pronóstico , Metástasis de la Neoplasia , Inmunohistoquímica , Anciano de 80 o más AñosRESUMEN
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.
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Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio <2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay. Although such patients are currently eligible for treatment with HER2-targeted therapy, their characteristics and outcomes remain poorly understood. Sixty-two BCs with equivocal HER2 immunohistochemical score (2+) and reflex ISH group 3 results were identified across 4 institutions. Available clinicopathologic characteristics, MammaPrint and BluePrint molecular results, and follow-up information were retrospectively analyzed. Most BCs with HER2 equivocal immunohistochemical and ISH group 3 results were histologic grade 2 or 3 (100%), estrogen receptor (ER) positive (90.3%), with an average HER2 signals/cell of 7.3. Molecular profiles revealed that 80% (16/20) of tumors were luminal subtypes, and HER2 molecular subtype was identified in 10% of tumors (2/20). Twelve (19.4%) out of 62 patients developed local recurrence and/or distant metastasis with a median follow-up of 50 months. One (10%) of 10 patients achieved pathologic complete response after neoadjuvant chemotherapy. Forty-nine (79%) out of 62 patients completed anti-HER2 agents, and exploratory analysis showed no statistically significant difference in disease outcomes between patients who completed anti-HER2 treatment and those who did not. Univariate analysis revealed advanced clinical stage, and ER/progesterone receptor negativity was associated with unfavorable disease outcomes, and exploratory multivariate analysis demonstrated that clinical stage was the most significant factor associated with disease outcomes in the studied population. These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.
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Biomarcadores de Tumor , Neoplasias de la Mama , Inmunohistoquímica , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/análisis , Persona de Mediana Edad , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Estudios Retrospectivos , Anciano de 80 o más Años , Hibridación in Situ , Cromosomas Humanos Par 17/genéticaRESUMEN
Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.
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Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratas , Animales , Ratas Sprague-Dawley , Accidente Cerebrovascular Isquémico/prevención & control , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Infarto de la Arteria Cerebral Media , Encéfalo/metabolismo , Proteínas Represoras , Factores de Transcripción Forkhead/metabolismoRESUMEN
Boosting charge separation and transfer of photoanodes is crucial for providing high viability of photoelectrochemical hydrogen (H2 ) generation. Here, a structural engineering strategy is designed and synthesized for uniformly coating an ultrathin CoFe bimetal-organic framework (CoFe MOF) layer over a BiVO4 photoanode for boosted charge separation and transfer. The photocurrent density of the optimized BiVO4 /CoFe MOF(NA) photoanode reaches a value of 3.92 mA cm-2 at 1.23 V versus reversible hydrogen electrode (RHE), up to 6.03 times that of pristine BiVO4 , due to the greatly increased efficiency of charge transfer and separation. In addition, this photoanode records one onset potential that is considerably shifted negatively when compared to BiVO4 . Transient absorption spectroscopy reveals that the CoFe MOF(NA) prolongs charge recombination lifetime by blocking the hole-transfer pathway from the BiVO4 to its surface trap states. This work sheds light on boosting charge separation and transfer through structural engineering to enhance the photocurrent of photoanodes for solar H2 production.
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Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.
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Formación de Anticuerpos , Vacunas contra la COVID-19 , COVID-19 , Nanopartículas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , Ratones , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
OBJECTIVE: To build T2WI-based multiregional radiomics for predicting tumor deposit (TD) and prognosis in patients with resectable rectal cancer. MATERIALS AND METHODS: A total of 208 patients with pathologically confirmed rectal cancer from two hospitals were prospectively enrolled. Intra- and peritumoral features were extracted separately from T2WI images and the least absolute shrinkage and selection operator was used to screen the most valuable radiomics features. Clinical-radiomics nomogram was developed by radiomics signatures and the most predictive clinical parameters. Prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis. RESULTS: For TD, the area under the receiver operating characteristic curve (AUC) for intratumoral radiomics model was 0.956, 0.823, and 0.860 in the training cohort, test cohort, and external validation cohort, respectively. AUC for the peritumoral radiomics model was 0.929, 0.906, and 0.773 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for combined intra- and peritumoral radiomics model was 0.976, 0.918, and 0.874 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for clinical-radiomics nomogram was 0.989, 0.777, and 0.870 in the training cohort, test cohort, and external validation cohort, respectively. The prognostic model constructed by combining intra- and peritumoral radiomics signature score (radscore)-based TD and MRI-reported lymph nodes metastasis (LNM) indicated good performance for predicting 3-year RFS, with AUC of 0.824, 0.865, and 0.738 in the training cohort, test cohort and external validation cohort, respectively. CONCLUSION: Combined intra- and peritumoral radiomics model showed good performance for predicting TD. Combining intra- and peritumoral radscore-based TD and MRI-reported LNM indicated the recurrence risk. CLINICAL RELEVANCE STATEMENT: Combined intra- and peritumoral radiomics model could help accurately predict tumor deposits. Combining this predictive model-based tumor deposits with MRI-reported lymph node metastasis was associated with relapse risk of rectal cancer after surgery. KEY POINTS: ⢠Combined intra- and peritumoral radiomics model provided better diagnostic performance than that of intratumoral and peritumoral radiomics model alone for predicting TD in rectal cancer. ⢠The predictive performance of the clinical-radiomics nomogram was not improved compared with the combined intra- and peritumoral radiomics model for predicting TD. ⢠The prognostic model constructed by combining intra- and peritumoral radscore-based TD and MRI-reported LNM showed good performance for assessing 3-year RFS.
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Extensión Extranodal , Neoplasias del Recto , Humanos , Pronóstico , Nomogramas , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Metástasis Linfática , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
MXene materials have become a competitive candidate for electrochemical energy storage due to their unique two-dimensional layered structure, high density, metal-like conductivity, fast ion intercalation, tunable surface terminal groups, and good mechanical flexibilities, showing unique application advantages in the field of supercapacitors. With widely research of MXene in energy storage applications, plenty of studies in synthesis strategies of MXene, including etching, intercalation and exfoliation processes, and its charge storage mechanism in supercapacitors have been conducted. However, the restacking of two-dimensional MXene nanosheets severely affects their electrochemical performance. To prevent the stacking of MXene, MXene-based nanocomposite electrode materials have been developed with remarkable electrochemical performance by incorporating conventional active capacitive materials, including metal oxides/sulfides and conductive polymers, with MXene. This review summarizes the etching strategies of MXenes and selection of intercalants, also discusses the charge storage mechanism of MXenes in aqueous and nonaqueous electrolytes. It mainly expounds the preparation strategies and applications of MXene-based nanocomposites in supercapacitors, including MXene/metal oxide, MXene/metal sulfide, MXene/conducting polymer, and MXene/carbon-based composites. Additionally, the advantages of combining MXene with other active materials in supercapacitor applications, which support its promising prospects, are discussed. Finally, the critical challenges faced by MXene-based nanocomposites in long-term research are mentioned.
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Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.
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Carcinoma de Células Renales , Quinasa de la Caseína I/genética , Neoplasias Renales , MicroARNs , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas , Inhibidor Tisular de Metaloproteinasa-3/genética , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer. MATERIALS AND METHODS: One hundred forty-six patients with rectal cancer who underwent preoperative MRI were prospectively enrolled. Two radiologists independently placed free-hand regions of interest (ROIs) in the largest tumor cross section and three small ROIs on the peritumoral zone adjacent to the tumor contour. Maximum values of tumor ADC (ADCtmax), minimum values of tumor ADC (ADCtmin), mean values of tumor ADC (ADCtmean), mean values of peritumor ADC (ADCpmean), and ADCpmean/ADCtmean (ADC ratio) were obtained on ADC maps and correlated with prognostic factors using uni- and multivariate logistic regression, and receiver operating characteristic curve (ROC) analysis. RESULTS: Interobserver agreement was excellent for ADCtmax and ADCtmean (intraclass correlation coefficient [ICC], 0.915-0.958), and were good for ADCtmin, ADCpmean, and ADC ratio (ICC, 0.774-0.878). The ADC ratio was significantly higher in the poor differentiation, T3-4 stage, lymph node metastasis (LNM)-positive, extranodal extension (ENE)-positive, tumor deposit (TD)-positive, and lymphovascular invasion (LVI)-positive groups than that in the well-moderate differentiation, T1-2 stage, LNM-negative, ENE-negative, TD-negative, and LVI-negative groups (p = 0.008, < 0.001, < 0.001, 0.001, < 0.001, and < 0.001, respectively). The area under the ROC curve (AUC) of the ADC ratio was the highest for assessing poor differentiation (0.700), T3-4 stage (0.707), LNM-positive (0.776), TD-positive (0.848), and LVI-positive (0.778). Both the ADC ratio (AUC = 0.677) and ADCpmean (AUC = 0.686) showed higher diagnostic performance for assessing ENE. CONCLUSION: The ADC ratio could provide better predictive performance for assessing preoperative prognostic factors in resectable rectal cancer. KEY POINTS: ⢠Both the peritumor/tumor ADC ratio and ADCpmean are correlated with important prognostic factors of resectable rectal cancer. ⢠Both peritumor ADC and peritumor/tumor ADC ratio had higher diagnostic performance than tumor ADC for assessment of prognostic factors in resectable rectal cancer. ⢠Peritumor/tumor ADC ratio showed the most capability for the assessment of prognostic factors in resectable rectal cancer.
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Imagen de Difusión por Resonancia Magnética , Neoplasias del Recto , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Pronóstico , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Estudios RetrospectivosRESUMEN
We previously showed that oral administration of exogenous glutathione (GSH) exerted a direct and/or indirect therapeutic effect on ischemic stroke rats, but the underlying mechanisms remain elusive. In the current study, we conducted a quantitative proteomic analysis to explore the pathways mediating the therapeutic effect of GSH in cerebral ischemia/reperfusion (I/R) model rats. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were treated with GSH (250 mg/kg, ig) or levodopa (L-dopa, 100 mg/kg, ig) plus carbidopa (10 mg/kg, ig). Neurologic deficits were assessed, and the rats were sacrificed at 24 h after cerebral I/R surgery to measure brain infarct sizes. We conducted a proteomic analysis of the lesion side striatum samples and found that tyrosine metabolism and dopaminergic synapse were involved in the occurrence of cerebral stroke and the therapeutic effect of GSH. Western blot assay revealed that tyrosine hydroxylase (TH) mediated the occurrence of I/R-induced ischemic stroke and the therapeutic effect of GSH. We analyzed the regulation of GSH on endogenous small molecule metabolites and showed that exogenous GSH had the most significant effect on intrastriatal dopamine (DA) in I/R model rats by promoting its synthesis and inhibiting its degradation. To further explore whether DA-related alterations were potential targets of GSH, we investigated the therapeutic effect of DA accumulation on ischemic brain injury. The combined administration of the precursor drugs of DA (L-dopa and carbidopa) significantly ameliorated neurological deficits, reduced infarct size, and oxidative stress, and decreased pro-inflammatory cytokines levels in the striatum of I/R injury rats. More interestingly, exogenous L-dopa/carbidopa could also greatly enhance the exposure of intracerebral GSH by upregulating GSH synthetases and enhancing homocysteine (HCY) levels in the striatum. Thus, administration of exogenous GSH exerts a therapeutic effect on ischemic stroke by increasing intrastriatal DA, and the accumulated DA can, in turn, enhance the exposure of GSH and its related substances, thus promoting the therapeutic effect of GSH.
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Dopamina/metabolismo , Glutatión/farmacología , Accidente Cerebrovascular Isquémico/patología , Animales , Carbidopa/farmacología , Citocinas/efectos de los fármacos , Modelos Animales de Enfermedad , Homocistina/efectos de los fármacos , Infarto de la Arteria Cerebral Media/patología , Levodopa/farmacología , Masculino , Estrés Oxidativo/genética , Proteómica , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Tirosina 3-Monooxigenasa/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Myelination is regulated by various glial cells in the central nervous system (CNS), including oligodendrocytes (OLs), microglia, and astrocytes. Myelination of the CNS requires the generation of functionally mature OLs from OPCs. OLs are the myelin-forming cells in the CNS. Microglia play both beneficial and detrimental roles during myelin damage and repair. Astrocyte is responsible for myelin formation and regeneration by direct interaction with oligodendrocyte lineage cells. These glial cells are influenced by experience-dependent activities such as environmental enrichment (EE). To date, there are few studies that have investigated the association between EE and glial cells. EE with a complex combination of sensorimotor, cognitive, and social stimulation has a significant effect on cognitive impairment and brain plasticity. Hence, one mechanism through EE improving cognitive function may rely on the mutual effect of EE and glial cells. The purpose of this paper is to review recent research into the efficacy of EE for myelination and glial cells at cellular and molecular levels and offers critical insights for future research directions of EE and the treatment of EE in cognitive impairment disease.
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Vaina de Mielina , Oligodendroglía , Sistema Nervioso Central/fisiología , Microglía , Vaina de Mielina/fisiología , Neuroglía , Oligodendroglía/fisiologíaRESUMEN
OBJECTIVE: To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) volume and apparent diffusion coefficient values (ADCs) for assessing lymph node metastases (LNM) and good response after chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This retrospective study consisted of 61 patients with LARC who underwent pre- and post-CRT DW images. Two radiologists independently placed free-hand regions of interest in each tumor-containing section on DW images to calculate pre- and post-CRT tumor volume and tumor volume reduction rates (Δvolume). Regions of interest were drawn to include tumor on maximum cross-sectional slice to obtain ADCs. Areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate diagnostic performance in identifying LNM and good response after CRT using these parameters. RESULTS: Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889-0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535-0.811). AUCs for identifying LNM were 0.508 for pre-CRT DW MR volume versus 0.705 for pre-CRT ADC, 0.855 for post-CRT DW MR volume versus 0.679 for post-CRT ADC, and 0.887 for Δvolume versus 0.533 for ΔADC. AUCs for identifying good response were 0.518 for pre-CRT volume versus 0.506 for pre-CRT ADC, 0.975 for post-CRT volume versus 0.723 for post-CRT ADC, and 0.987 for Δvolume versus 0.655 for ΔADC. CONCLUSION: DW MR Δvolume provided high diagnostic performance in discriminating LNM after CRT. DW MR Δvolume was equally as accurate as post-CRT DW MR volume for evaluating good response. KEY POINTS: ⢠Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889-0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535-0.811). ⢠DW MR Δvolume provided high diagnostic performance in identifying LNM after CRT (AUC, 0.887) and good response (AUC, 0.987) and was significantly more accurate than pre-CRT DW MR volume (AUC, 0.508 and 0.518, respectively) and ADCs (AUC, 0.705 and 0.506, respectively). ⢠DW MR Δvolume (AUC, 0.987) was equally as accurate as post-CRT DW MR volume (AUC, 0.975) for evaluating good response, while pre-CRT DW MR volume and ADCs were not reliable for evaluating LNM and good response after CRT (AUC, 0.506-0.723).
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Neoplasias del Recto , Estudios Transversales , Imagen de Difusión por Resonancia Magnética , Humanos , Metástasis Linfática , Espectroscopía de Resonancia Magnética , Terapia Neoadyuvante , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO2 (H-MnO2). The highly monodisperse H-MnO2 with uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study.
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Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Compuestos de Manganeso/química , Sistema de Administración de Fármacos con Nanopartículas/química , Óxidos/química , Polietilenglicoles/química , Dióxido de Silicio/química , Animales , Apoptosis/efectos de los fármacos , Conducta Animal , Modelos Animales de Enfermedad , Liberación de Fármacos , Humanos , Masculino , Prueba del Laberinto Acuático de Morris , Sistema de Administración de Fármacos con Nanopartículas/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/efectos adversos , Ratas , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
BACKGROUND: Since the outbreak of the SARS-CoV-2 virus in December 2019, the COVID-19 pandemic continues to threaten global stability. Transmission of SARS-CoV-2 is mostly by respiratory droplets and direct contact but viral RNA fragments have also been detected in the faecal waste of patients with COVID-19. Cleanliness and effective sanitation of public toilets is a concern, as flushing the toilet is potentially an aerosol generating procedure. When the toilets are of the squatting type and without a cover, there exists a risk of viral contamination through the splashing of toilet water and aerosol generation. OBJECTIVE: This study aims to determine whether the cleanliness of public toilets was a concern to the general population during the COVID-19 pandemic, and whether a squatting toilet was preferred to a seated design. METHODS: A questionnaire was designed and posted on "WeChat" contact groups of the investigators. RESULTS: The survey showed that 91% of participants preferred squatting toilets, but that 72% were apprehensive of personal contamination when using public toilets. Over 63% of the respondents had encountered an incidence of water splash and would prefer public toilets to be covered during flushing and 83% of these respondents preferred a foot-controlled device. CONCLUSION: This survey suggests that consideration should be given to the installation of a simple foot-controlled device to cover public squatting toilets to help restrict potential COVID-19 contamination and to meet hygienic expectations of the public.
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The design on synthesizing a sturdy, low-cost, clean, and sustainable electrocatalyst, as well as achieving high performance with low overpotential and good durability toward water splitting, is fairly vital in environmental and energy-related subject. Herein, for the first time the growth of sulfur (S) defect engineered self-supporting array electrode composed of metallic Re and ReS2 nanosheets on carbon cloth (referred as Re/ReS2 /CC) via a facile hydrothermal method and the following thermal treatment with H2 /N2 flow is reported. It is expected that, for example, the as-prepared Re/ReS2 -7H/CC for the electrocatalytic hydrogen evolution reaction (HER) under acidic medium affords a quite low overpotential of 42 mV to achieve a current density of 10 mA cm-2 and a very small Tafel slope of 36 mV decade-1 , which are comparable to some of the promising HER catalysts. Furthermore, in the two-electrode system, a small cell voltage of 1.30 V is recorded under alkaline condition. Characterizations and density functional theory results expound that the introduced S defects in Re/ReS2 -7H/CC can offer abundant active sites to advantageously capture electron, enhance the electron transport capacity, and weaken the adsorption free energy of H* at the active sites, being responsible for its superior electrocatalytic performance.
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BACKGROUND: Thymic carcinoma is a rare mediastinal neoplasm with a high malignant potential. It often shows pleural invasion and distant metastasis. The metastasis of thymic carcinoma to the small intestine is rarely reported and difficult to distinguish from other gastrointestinal tract tumors. CASE PRESENTATION: An elderly man presented with lower abdominal pain for 2 months. Abdominal CT showed a mass communicated with the small intestinal lumen. After radical resection of the small intestinal tumor, resected specimens showed moderately differentiated squamous-cell carcinoma with lymph nodes metastases. The patient received chest CT and was found to have a mass in anterior mediastinum. Biopsies of the mass revealed thymic squamous-cell carcinoma. CONCLUSIONS: We highlighted the metastasis of thymic carcinoma to the small intestine is rare and easily misdiagnosed. In patients with a mass communicated with the small intestinal lumen, a suspicion of thymic carcinoma metastasis should not be overlooked and we should make accurate differential diagnosis from the other small intestinal tumors.
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Carcinoma de Células Escamosas , Timoma , Neoplasias del Timo , Anciano , Humanos , Intestino Delgado , Metástasis Linfática , Masculino , Timoma/diagnóstico por imagen , Timoma/cirugía , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/cirugíaRESUMEN
The laser performance of a high-power ytterbium-doped fiber amplifier is mainly hindered by the onset of mode instability. In this work, the slope efficiency and mode instability threshold of the ytterbium-doped fiber under various gamma-ray radiation doses have been measured. Experimental results reveal that gamma-ray radiation-induced photodarkening degrades mode instability severely, and gamma-ray radiation-induced mode instability degradation can be partly bleached by hours of pump-light injection. It is shown that gamma-ray radiation-induced photodarkening results in a steep reduction of slope efficiency and mode instability threshold; moreover, the entire irradiated fiber can be partly bleached by hours of pump-light injection and exhibits both time and gamma-ray radiation-dose saturation properties. The experimental results indicate that mode instability mitigation can be partly realized by pump-light injection and implies photodarkening suppression is beneficial for TMI mitigation, which is very promising for the advancement of high-power fiber lasers.
RESUMEN
Nucleophosmin (NPM1), a restricted nucleolar localization protein, shuttles between the nucleus and the cytoplasm. Mutated (Mt)-NPM1 protein, which has aberrant cytoplasmic dislocation of nucleophosmin, occurs in approximately one-third of acute myeloid leukemia cases. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent. NOD/SCID mice xenografted with human Mt-NPM1 OCI/AML3 cell lines served as in-vivo models. Wright-Giemsa staining and flow cytometry analysis were used for differentiation assays. Associated molecular events were assessed by western blot and histological analyses. Kaplan-Meier estimates were used to calculate survival. Deguelin toxicity in mice was assessed by immunohistochemistry staining and serum markers. Clinical samples were differentiated by flow cytometry analysis. Deguelin induced differentiation by downregulating the Mt-NPM1 protein levels, which was accompanied by a decrease in SIRT1, p21, and HDAC1 and an increase in CEBPß and granulocyte colony-stimulating factor receptor protein expression levels. A low-deguelin dose prolonged survival compared with the control group, and there were no apparent lesions to the brain, liver, heart, and kidney in vivo. In clinical samples, deguelin induced the differentiation of fresh blasts with Mt-NPM1 protein, but not with the wild-type NPM1 protein. Taken together, these findings further provide new evidence that the Mt-NPM1 protein plays an important role in inducing differentiation in vivo and in vitro. Mutated NPM1 protein may be a therapeutic target of deguelin in acute myeloid leukemia with the NPM1 mutation.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Rotenona/análogos & derivados , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Nucleofosmina , Distribución Aleatoria , Rotenona/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We have developed an extreme ultraviolet (EUV) scatterometer based on the analysis of coherent EUV light diffracted from a periodic array with nano-scale features. We discuss the choice of appropriate orders of the high harmonics generated coaxially along with the intense Ti:sapphire laser pulses for high resolution spatial performance. We describe an inverse-problem methodology for determining the structural parameters, and present preliminary measurement results confirming the functionality of the scatterometer. A rigorous coupled-wave analysis measurement algorithm was developed to extract accurately and quickly the relevant constitutive parameters from a measured diffraction pattern using a library-matching process.