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BACKGROUND: Pulmonary perfusion defects have been observed in patients with coronavirus disease 2019 (COVID-19). Currently, there is a need for further data on non-contrast-enhanced MRI in COVID patients. The early identification of heterogeneity in pulmonary perfusion defects among COVID-19 patients is beneficial for their timely clinical intervention and management. PURPOSE: To investigate the utility of phase-resolved functional lung (PREFUL) MRI in detecting pulmonary perfusion disturbances in individuals with postacute COVID-19 syndrome (PACS). STUDY TYPE: Prospective. SUBJECTS: Forty-four participants (19 females, mean age 64.1 years) with PACS and 44 healthy subjects (19 females, mean age 59.5 years). Moreover, among the 44 patients, there were 19 inpatients and 25 outpatients; 19 were female and 25 were male; 18 with non-dyspnea and 26 with dyspnea. FIELD STRENGTH/SEQUENCE: 3-T, two-dimensional (2D) spoiled gradient-echo sequence. ASSESSMENT: Ventilation and perfusion-weighted maps were extracted from five coronal slices using PREFUL analysis. Subsequently, perfusion defect percentage (QDP), ventilation defect percentage (VDP), and ventilation-perfusion match healthy (VQM) were calculated based on segmented lung parenchyma ventilation and perfusion-weighted maps. Additionally, clinical features, including demographic data (such as sex and age) and serum biomarkers (such as D-dimer levels), were evaluated. STATISTICAL TESTS: Spearman correlation coefficients to explore relationships between clinical features and QDP, VDP, and VQM. Propensity score matching analysis to reduce the confounding bias between patients with PACS and healthy controls. The Mann-Whitney U tests and Chi-squared tests to detect differences between groups. Multivariable linear regression analyses to identify factors related to QDP, VDP, and VQM. A P-value <0.05 was considered statistically significant. RESULTS: QDP significantly exceeded that of healthy controls in individuals with PACS (39.8% ± 15.0% vs. 11.0% ± 4.9%) and was significantly higher in inpatients than in outpatients (46.8% ± 17.0% vs. 34.5% ± 10.8%). Moreover, males exhibited pulmonary perfusion defects significantly more frequently than females (43.9% ± 16.8% vs. 34.4% ± 10.2%), and dyspneic participants displayed significantly higher perfusion defects than non-dyspneic patients (44.8% ± 15.8% vs. 32.6% ± 10.3%). QDP showed a significant positive relationship with age (ß = 0.50) and D-dimer level (ß = 0.72). DATA CONCLUSION: PREFUL MRI may show pulmonary perfusion defects in patients with PACS. Furthermore, perfusion impairments may be more pronounced in males, inpatients, and dyspneic patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Improving visible light absorption plays an important role in the utilization of solar power for photocatalysis. Using first-principles calculations within the HSE06 functional, we propose that the semiconductor heterojunction BiOI/LaOXIãIXã extends the optical absorption to the near-infrared range, boosts the absorption coefficient from 1.28 × 105 cm-1 to above 2.20 × 105 cm-1 in the visible light range, and increases the conversion efficiency of solar power up to 9.48%. The enhanced optical absorption derives from the significant interlayer transition and excitonic effect which benefit from polarized LaOXI with a flat band in the highest valence band (VB). In BiOI/LaOClIãICl ã, the electrostatic potential difference (ΔΦ) modifies the band edge positions to meet the requirements for photocatalytic overall water splitting, while the polarized electric field (Ep) accelerates the separation of photogenerated carriers and regulates the overpotentials of photogenerated carriers following a direct Z-scheme strategy. In addition, BiOI/LaOXIãIXã is dynamically and thermodynamically stable. Furthermore, only a low external potential is needed to drive the redox reaction. Our theoretical results suggest that BiOI/LaOXIãIXã could be a potential photocatalyst for overall water splitting with enhanced visible light absorption.
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The negative Poisson's ratio (NPR) effect usually endows materials with promising ductility and shear resistance, facilitating a wider range of applications. It has been generally acknowledged that alloys show strong advantages in manipulating material properties. Thus, a thought-provoking question arises: how does alloying affect the NPR? In this paper, based on first-principles calculations, we systematically study the NPR in two-dimensional (2D) GaN and AlN, and their alloy of AlxGa1-xN. It is intriguing to find that the NPR in AlxGa1-xN is significantly enhanced compared to the parent materials of GaN and AlN. The underlying mechanism mainly originates from a counter-intuitive increase of the bond angle θ. We further study the microscopic origin of the anomalies by electron orbital analysis as well as electron localization functions. It is revealed that the distribution and movement of electrons change with the applied strain, providing a fundamental view on the effect of strain on lattice parameters and the NPR. The physical origin as revealed in this study deepens the understanding of the NPR and shed light on the future design of modern nanoscale electromechanical devices with fantastic functions based on the auxetic nanomaterials and nanostructures.
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BACKGROUND: Recent studies have drawn attention to the association between preserved ratio impaired spirometry (PRISm) and cognitive function decline. High systolic blood pressure (SBP) is a known risk factor for both PRISm and dementia. This study aimed to investigate whether elevated SBP may mediate the relationship between PRISm and cognitive function in older adults. METHODS: This study analyzed 732 participants aged ≥ 60 years who had completed spirometry and cognitive function tests in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Multivariable linear regression was employed to assess the relationship between PRISm and cognitive function, as measured through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, the Animal Fluency test (AFT), the Digit Symbol Substitution test (DSST), and global cognition tests. All cognitive tests were modeled as z-scores, and global cognition was calculated as the sum of the z-scores of the CERAD, AFT, and DSST. Mediation analyses were conducted to test the mediating effect of SBP on the association between PRISm and cognitive function. RESULTS: Participants with PRISm had lower AFT (ß = -0.300; 95% confidence interval [CI] = -0.479 to -0.122; p = 0.001), DSST (ß = -0.157; 95% CI = -0.309 to -0.004; p = 0.044), and global cognition scores (ß = -0.211; 95% CI = -0.369 to -0.053; p = 0.009) than those with normal spirometry, after adjusting for all potential confounders. SBP was considerably associated with AFT (ß = -0.084; 95% CI = -0.162 to -0.005; p = 0.038) and DSST (ß = -0.132; 95% CI = -0.207 to -0.057; p < 0.001), mediating 7.9% and 18.0% of the association of PRISm with cognitive function, respectively. Furthermore, SBP mediated 17.1% of the association of PRISm with global cognition. CONCLUSIONS: The findings suggested the potential role of SBP as a mediator of associations between PRISm and cognitive decline in older adults.
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Presión Sanguínea , Cognición , Encuestas Nutricionales , Espirometría , Humanos , Masculino , Femenino , Anciano , Espirometría/métodos , Encuestas Nutricionales/métodos , Cognición/fisiología , Presión Sanguínea/fisiología , Estados Unidos/epidemiología , Persona de Mediana Edad , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Disfunción Cognitiva/fisiopatología , Anciano de 80 o más Años , Estudios TransversalesRESUMEN
BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estudios Prospectivos , Terapia Neoadyuvante/métodos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Ganglios Linfáticos/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: To investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models. MATERIALS AND METHODS: Subcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured. RESULTS: The optimal viral titer of OH2 was 1 × 107 CCID50. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies. CONCLUSION: TAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice. DATA AVAILABILITY: Data is available from the corresponding author upon requirement.
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Embolización Terapéutica , Neoplasias Hepáticas , Animales , Conejos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.
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Neoplasias de la Mama , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Estudios Prospectivos , Receptor ErbB-2/genéticaRESUMEN
BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an enveloped positive-sense ssRNA virus which is highly lethal to piglets, causing enormous economic losses to swine industry worldwide. Nsp15 protein is an endoribonuclease of PEDV and plays an indispensable role in the viral proliferation. We reported the transcription files of nsp15 transfected IPEC-J2 cells for the first time to broaden our understanding of PEDV pathogenesis. METHODS: RNA-seq was performed to compare gene expression profiles between pCAGGS-HA-nsp15 transfected IPEC-J2 cells and pCAGGS-HA (empty vector) transfected IPEC-J2 cells. Immune-related genes and pathways were identified and analyzed to deepen our understanding of nsp15 for PEDV pathogenicity. IPEC-J2 cells transfected with pCAGGS-HA-CCL5/CXCL8/CXCL10 were infected with CV777 and the virus load of PEDV was detected by qRT-PCR. RESULTS: A total of 21,654 genes were obtained by RNA-Seq and 415 differential expressed genes (DEGs) were identified, including 136 up-regulated and 279 down-regulated genes. A number of effect genes involved in immune responses and inflammation were differentially expressed. GO and KEGG enrichment analysis showed that 32 GO terms were significantly enriched and the DEGs were mainly enriched in immune-related pathways such as TNF signaling pathway, RIG-I-like receptor signaling pathway and Cytosolic DNA-sensing pathway. qRT-PCR results indicated the overexpression of selected chemokines, CCL5/CXCL8/CXCL10, can inhibit PEDV proliferation in IPEC-J2 cells. CONCLUSIONS: Our transcriptome profile illustrated a number of genes involving in immune responses and inflammation were inhibited by nsp15, such as CCL5, CXCL8, CXCL10, OAS, MXs, STAT1 and IRF9. The results suggested that nsp15 can antagonize IFNs and block chemokine system to provide an adequate intracellular environment for viral proliferation.
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Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Animales , Línea Celular , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/veterinaria , Células Epiteliales , Perfilación de la Expresión Génica , Inmunidad , Virus de la Diarrea Epidémica Porcina/genética , PorcinosRESUMEN
BACKGROUND: The association between the type of anesthesia used and the recurrence of cancer remains controversial. This study aimed to compare the effects of local vs general anesthesia on recurrence-free survival and cost after breast-conserving surgery. MATERIALS AND METHODS: We reviewed the data of 2778 patients who underwent breast-conserving surgery followed by radiation at our center between 1999 and 2014. We analyzed the data of 994 patients with hormone receptor-positive and Her2-negative tumors who underwent breast-conserving surgery without axillary lymph node dissection under local or general anesthesia. Patients were grouped according to whether local or general anesthesia was used for the surgery. RESULTS: Of the 994 patients enrolled in this study, 367 received local anesthesia and 627 patients received general anesthesia. The median follow-up duration for all patients was 93 months. The Kaplan-Meier survival curves did not reveal significant differences between the recurrence-free survival of the two groups, with 5-year recurrence-free survival rates of 96.3% (95% CI, 94.3-98.3%) in the local anesthesia group and 97.3% (95% CI, 95.9-98.7%) in the general anesthesia group. The total cost of hospitalization in the local anesthesia group was significantly lower than that in the general anesthesia group (P <.001). The difference in the cost between the two groups remained significant, irrespective of the type of hospitalization, after excluding 165 patients receiving chemotherapy during their hospitalization. CONCLUSIONS: Our analysis indicated no association between the type of anesthesia used during breast-conserving surgery and the long-term prognosis of breast cancer. However, breast-conserving surgery under local anesthesia may be a less expensive option than that under general anesthesia.
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Neoplasias de la Mama , Mastectomía Segmentaria , Anestesia General , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia/patología , Estudios RetrospectivosRESUMEN
AIM: To investigate the change of tumor feeding artery diameter and the efficacy of metastasis inhibition after transarterial chemoembolization (TACE) combined with apatinib or TACE monotherapy for patients with advanced hepatocellular carcinoma who without metastasis. MATERIALS AND METHODS: A total of 616 consecutive patients who received the treatment of TACE-apatinib or TACE in our center was enrolled. Propensity score matching (PSM) analysis was used to reduce bias. The overall survival (OS), OS-after-metastasis (OSM), time to progression (TTP), time to metastasis (TTM), time to vessel or organ metastasis (TVOM), time to lymph node metastasis, and tumor feeding artery diameter between the two treatment groups were compared. RESULTS: A total of 113 pairs of patients were eligible after the PSM. Time to lymph node metastasis between the two groups was not significantly different (P > 0.05). The tumor feeding artery diameter was significantly smaller after TACE-apatinib management (P < 0.001). Median OS (P < 0.001) and OSM (P < 0.001) were significantly longer in the TACE-apatinib group compared with the TACE group. Median TTP (P < 0.001), TTM (P < 0.001), and TVOM (P < 0.001) were significantly prolonged in TACE-apatinib group. CONCLUSION: TACE-apatinib treatment could improve the prognosis compared with TACE alone, and inhibit metastasis after TACE procedure with contracted tumor feeding artery for advanced HCCs without metastasis.
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In layered materials with the stacking axis perpendicular to the basal plane, anharmonicity strongly affects phonon propagation due to weak interlayer coupling, which is helpful to reduce the lattice thermal conductivity and improve the thermoelectric (TE) performance significantly. By combining first-principles calculations and the Boltzmann transport equation, we systematically analyzed and evaluated the lattice thermal conductivity and TE properties of LaMOCh (M = Cu, Ag; Ch = S, Se). The results indicate that these layered materials exhibit ultralow lattice thermal conductivities of 0.24-0.37 W m-1 K-1 along the interlayer direction at room temperature. The low lattice thermal conductivities have been analyzed from some inherent phonon properties, such as low acoustic phonon group velocity, large Grüneisen parameters, and a short phonon relaxation time. Originating from their natural layered crystal structure, the thermal and electronic transports (i.e., thermal conductivity, Seebeck coefficient, and electrical conductivity) are both highly anisotropic between their intralayer and interlayer directions. Finally, we obtained ZT values of 1.17 and 1.26 at 900 K along the interlayer direction for n-type LaCuOSe and LaAgOSe, respectively. Generally, LaMOSe exhibit larger anisotropy than LaMOS, in both n- and p-types of doping. Our findings of low thermal conductivities and large anisotropic TE performances of these layered systems should stimulate much attention in BiCuOSe and alike layered TE families.
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PURPOSE: In subarachnoid hemorrhage, noncontrast CT features are used to guide the localization of ruptured aneurysms on CT angiography and DSA. Multiplanar CT may improve the localization of aneurysm rupture sites over axial plane CT alone. METHODS: Multiplanar CT in three orthogonal planes was used to evaluate 94 cases of SAH. Two investigators independently evaluated each imaging plane for focal thick SAH with mass effect, intracerebral hemorrhage, focal edema, filling defect, subdural hemorrhage, and dominant intraventricular hemorrhage. Also, rupture site was qualitatively identified by combining these variables in each plane and combination of three planes. DSA served as the gold standard to locate the rupture sites. RESULTS: Interobserver agreement was k 0.60 to 0.79 for axial, k 0.43 to 0.86 for coronal and k 0.43 to 0.74 for sagittal planes. Good to substantial agreement was observed for the localization of rupture site in three planes (focal SAH with mass effect - k 0.78 to 0.85; filling defect - k 0.95 to 1.0; intracerebral hemorrhage - k 1.0; focal edema k 1.0; subdural hemorrhage - k 0.61 to 0.83). Dominant intraventricular hemorrhage revealed significant association with DSA to locate ruptured aneurysms (Fisher's exact test - Pr < = P (< 0.001)). With non-missing data, frequency of correct ratings to locate rupture site was 66/67 (99%) in axial plane, 59/66 (89%) in coronal plane, 64/67 (96%) in sagittal plane and 77/77 (100%) in combined 3 planes. CONCLUSIONS: Multiplanar CT head is more successful than axial plane CT alone for the localization of aneurysm rupture sites in SAH.
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Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Aneurisma Roto/complicaciones , Aneurisma Roto/diagnóstico por imagen , Angiografía Cerebral/métodos , Hemorragia Cerebral/complicaciones , Hematoma Subdural , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
Whether adding carboplatin to standard neoadjuvant chemotherapy improves survival in BRCA1/2-mutated triple-negative breast cancer (TNBC) is unknown. In this retrospective study, we aimed to explore the efficacy of anthracycline-taxane (A-T)-based or anthracycline-taxane/carboplatin (A-TP)-based neoadjuvant chemotherapy in BRCA1/2-mutated TNBC. A total of 1585 operable primary breast cancer patients were treated with either neoadjuvant A-T (n = 886) or A-TP regimen (n = 699). BRCA1 and BRCA2 germline mutations were determined in all subjects. Pathological complete response (pCR), recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and overall survival (OS) were estimated. Of the entire cohort, 102 patients (6.4%) carried a pathogenic BRCA1/2 germline mutation. After a median follow-up of 81 months, no significant differences in survival between the A-T and A-TP arms were found in the entire cohort. However, among 288 TNBC patients, BRCA1/2 mutation carriers had significantly better survival when treated with the A-TP regimen than with the A-T regimen (5-year RFS: 82.6% vs 47.9%; P = .024; 5-year DRFS: 88.5% vs 46.9%; P = .010; 5-year OS: 88.2% vs 49.9%; P = .036). Multivariate analyses revealed that the A-TP regimen was a significantly favourable factor for RFS and DRFS and showed a trend towards better OS when compared with the A-T regimen in BRCA1/2-mutated TNBC (RFS: adjusted hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.06-0.91, P = .035; DRFS: HR, 0.17; 95% CI, 0.03-0.80; P = .025; OS: HR, 0.29; 95% CI, 0.06-1.49; P = .14). Our study suggested that BRCA1/2-mutated TNBC patients gain a survival benefit when carboplatin is added to standard A-T-based neoadjuvant chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación de Línea Germinal , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Antraciclinas/administración & dosificación , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Carboplatino/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Taxoides/administración & dosificación , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Adulto JovenRESUMEN
A number of positive-strand RNA viruses, such as hepatitis C virus (HCV) and poliovirus, use double-membrane vesicles (DMVs) as replication sites. However, the role of cellular proteins in DMV formation during virus replication is poorly understood. HCV NS4B protein induces the formation of a "membranous web" structure that provides a platform for the assembly of viral replication complexes. Our previous screen of NS4B-associated host membrane proteins by dual-affinity purification, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and small interfering RNA (siRNA) methods revealed that the Surfeit 4 (Surf4) gene, which encodes an integral membrane protein, is involved in the replication of the JFH1 subgenomic replicon. Here, we investigated in detail the effect of Surf4 on HCV replication. Surf4 affects HCV replication in a genotype-independent manner, whereas HCV replication does not alter Surf4 expression. The influence of Surf4 on HCV replication indicates that while Surf4 regulates replication, it has no effect on entry, translation, assembly, or release. Analysis of the underlying mechanism showed that Surf4 is recruited into HCV RNA replication complexes by NS4B and is involved in the formation of DMVs and the structural integrity of RNA replication complexes. Surf4 also participates in the replication of poliovirus, which uses DMVs as replication sites, but it has no effect on the replication of dengue virus, which uses invaginated/sphere-type vesicles as replication sites. These findings clearly show that Surf4 is a novel cofactor that is involved in the replication of positive-strand RNA viruses using DMVs as RNA replication sites, which provides valuable clues for DMV formation during positive-strand RNA virus replication.IMPORTANCE Hepatitis C virus (HCV) NS4B protein induces the formation of a membranous web (MW) structure that provides a platform for the assembly of viral replication complexes. The main constituents of the MW are double-membrane vesicles (DMVs). Here, we found that the cellular protein Surf4, which maintains endoplasmic reticulum (ER)-Golgi intermediate compartments and the Golgi compartment, is recruited into HCV RNA replication complexes by NS4B and is involved in the formation of DMVs. Moreover, Surf4 participates in the replication of poliovirus, which uses DMVs as replication sites, but has no effect on the replication of dengue virus, which uses invaginated vesicles as replication sites. These results indicate that the cellular protein Surf4 is involved in the replication of positive-strand RNA viruses that use DMVs as RNA replication sites, providing new insights into DMV formation during virus replication and potential targets for the diagnosis and treatment of positive-strand RNA viruses.
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Estructuras de la Membrana Celular/metabolismo , Hepacivirus/fisiología , Proteínas de la Membrana/metabolismo , ARN Viral/biosíntesis , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/fisiología , Línea Celular Tumoral , Estructuras de la Membrana Celular/genética , Estructuras de la Membrana Celular/virología , Genotipo , Humanos , Proteínas de la Membrana/genética , ARN Viral/genética , Proteínas no Estructurales Virales/genéticaRESUMEN
By means of quotient-graph associated crystal prediction method, a new graphyne allotrope with unique Dirac nodal grid state is reported in this work. It is named as 191-E24Y24-1 according to its hexagonal lattice (with P6/mmm symmetry, No. 191) containing 24 sp2-hybridized carbon atoms and 24 sp-hybridized ones. The first-principles results show that the total energy of 191-E24Y24-1 is more favorable than that of recent synthesizedß-graphdiyne and carbon ene-yne. It is also demonstrated to be dynamically, thermally, and mechanically stable. Interestingly, the 191-E24Y24-1 harbors intrinsic semimetal features showing intriguing hexagonal Dirac nodal grid state in the reciprocal space. Such unique electronic state is stable against small external tensile strains, and it is tunable under compression strains which will transform to new triangle Dirac nodal grid state. Moreover, a new metastable graphyne allotrope named 191-E12Y36-4 with Dirac nodal loop state is also observed in the process of stretching 191-E24Y24-1 with large tensile strains. The results presented in this work reveal two novel graphyne allotropes with exotic electronic properties. These discoveries are not only physical interesting, but also provide potential material candidates for carbon-based high performance electronic nanodevices.
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Defects caused by the structural disorder of perovskites and voltage loss resulting from mismatched band structure are important issues to address to improve the performance of carbon-based perovskite solar cells. Different from the conventional approaches of additive-based passivation of perovskite precursors and introducing a hole-transport layer between the perovskite layer and carbon electrode, herein we report a defect-healing method using phenethyl ammonium iodide (PEAI) treatment and band-structure modification using high-work-function inorganic copper phthalocyanine (CuPc). Because of its relatively smoother surfaces and lower defect content, the optimized device after PEAI-based passivation of the perovskite achieves a power conversion efficiency (PCE) of 11.74%. The PCE is further raised to 13.41% through the auxiliary energy-level matching and high hole extraction abilities of the CuPc-modified carbon electrode. The best-performing device exhibits excellent moisture tolerance and thermal stability with minor current density-voltage hysteresis.
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The state-of-the-art perovskite solar cells (PSCs) with SnO2 electron transporting material (ETL) layer displays the probability of conquering the low electron mobility and serious leakage current loss of the TiO2 ETL layer in photoelectronic devices. The rapid development of SnO2 ETL layer has brought perovskite efficiencies >20%. However, high density of defect states and voltage loss of high temperature SnO2 are still latent impediment for the long-term stability and hysteresis effect of photovoltaics. Herein, Nb5+ doped SnO2 with deeper energy level is utilized as a compact ETL for printable mesoscopic PSCs. It promotes carrier concentration increase caused by n-type doping, assists Fermi energy level and conduction band minimum to move the deeper energy level, and significantly reduces interface carrier recombination, thus increasing the photovoltage of the device. As a result, the use of Nb5+ doped SnO2 brings high photovoltage of 0.92 V, which is 40 mV higher than that of 0.88 V for device based on SnO2 compact layer. The resulting PSCs displays outstanding efficiency of 13.53%, which contains an â¼10% improvements compared to those without Nb5+ doping. Our study emphasizes the significance of element doping for compact layer and lays the groundwork for high efficiency PSCs.
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Correction for 'Ultra-high thermal conductivities of tetrahedral carbon allotropes with non-simple structures' by Qiang Chen et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d1cp02347k.
RESUMEN
Pursuing high thermal conductivity is of great significance to enhance the performance and working stability of microelectronics in terms of efficient heat dissipation. Traditionally, ultra-high thermal conductivity is thought to exist only in simple crystals with few atoms in the primitive cell, such as diamond and boron arsenide, where the phonon-phonon scattering is weak. In this study, we report an innovation from conventional knowledge based on state-of-the-art first-principles calculations. It is found that the thermal conductivities of three carbon allotropes of C32, C36, and C94 with non-simple structures can be as high as 1152.75, 1075.70, and 860.07 W m-1 K-1, respectively, despite a large number of atoms in the primitive cell. Through comparative analysis, it is revealed that there exist certain competitive mechanisms, where the weak phonon anharmonicity is found to dominate the high thermal conductivity. Our study not only uncovers excellent carbon-based candidates with ultra-high thermal conductivity for enhancing heat dissipation with potential applications in electronics, but also provides insights into the thermal transport, which will shed light on future studies.
RESUMEN
Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.