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1.
J Control Release ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278354

RESUMEN

Islet-antigen-specific tolerization is a key goal of experimental immunotherapies for type 1 diabetes. mRNA-based vaccines have demonstrated the feasibility of RNA delivery in inducing antigen tolerance in autoimmune diseases. In this study, mRNA vaccine, encoded tandem glutamic acid decarboxylase 65 (GAD65) epitopes and cholera toxin B subunit (CTB-GADIII), prepared by an in vitro transcription (IVT) system and encapsulated with lipid nanoparticles (LNP), was intramuscularly administered to nonobese diabetic (NOD) and Cyclophosphamide (Cy)-NOD mice respectively. The results showed that the mRNA vaccines significantly reduced the incidence rate of type 1 diabetes, delayed the disease progression, improved glucose tolerance, and protected pancreatic morphology and function compared with the controls. Meanwhile, the vaccines also reduced the levels of autoantibodies to glutamic acid decarboxylase (GADA) and insulin (IAA) in the serum. Furthermore, the proportion of CD4+ T helper cell subsets was modulated in the spleen of mice treated with mRNA vaccines, in correspondence with the increased levels of IL-10 and TGF-ß in serum, suggesting the possible mechanism of immune tolerance. This study provides experimental evidence for the application of mRNA vaccines encoding self-antigens in the prevention or treatment of type 1 diabetes.

2.
Angew Chem Int Ed Engl ; : e202412590, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180505

RESUMEN

As the initial synthesized colloidal quantum dots (CQDs) are generally capped with insulating ligands, ligand exchange strategies are essential in the fabrication of CQD films for solar cells, which can regulate the surface chemical states of CQDs to make them more suitable for thin-film optoelectronic devices. However, uncontrollable surface adsorption of water molecules during the ligand exchange process introduces new defect sites, thereby impairing the resultant device performance, which attracts more efforts devoted to it but remains a puzzle. Here, we develop a solvent-engineering-assisted ligand exchange strategy to revamp the surface adsorption, improve the exchange efficiency, and modulate the surface chemistry for the environmentally friendly lead-free silver bismuth disulfide (AgBiS2) CQDs. The optimized AgBiS2 CQD solar cells deliver an outstanding champion power conversion efficiency (PCE) of up to 8.95% and improved long-term stability. Our strategy is less environment-dependent and can produce solar cells with negligible performance variance for several batches across several months. Our work demonstrates the critical role of solvents for ligand exchange in the surface chemistry of CQDs and the realization of high-performance photovoltaic devices in a highly reproducible manner.

3.
Front Oncol ; 14: 1366613, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38826784

RESUMEN

Purpose: To investigate what pre-treatment clinical-pathological features and MRI characteristics influence the performance of breast MRI in assessing the pathologic complete response (pCR) of breast cancer patients to Neoadjuvant Chemotherapy (NAC). Methods: A total of 225 patients with pathologically-confirmed breast cancer who underwent pre- and post-NAC breast MRI between January 2020 and April 2023 were retrospectively analyzed. All patients were categorized into radiologic complete response (rCR) and non-rCR groups based on pre-operative MRI. Univariable and multivariable logistic regression were used to identify independent clinicopathological and imaging features associated with imaging-pathological discordance. The performance of pre-operative MRI for predicting pCR to NAC was assessed according to the baseline characteristics of the clinicopathological data and pre-NAC MRI. In addition, the discrepancy between the pre-operative MRI and post-operative pathological findings was further analyzed by a case-control approach. Results: Among 225 patients, 99 (44.0%) achieved pCR after NAC. MRI showed the overall sensitivity of 97.6%, specificity of 58.6%, accuracy of 80.4%, a positive predictive value (PPV) of 75.0%, and a negative predictive value (NPV) of 95.1% in identifying pCR. Of baseline features, presence of ductal carcinoma in situ (DCIS) (OR, 3.975 [95% CI: 1.448-10.908], p = 0.007), luminal B (OR, 5.076 [95% CI: 1.401-18.391], p = 0.013), HER2-enriched subtype (OR, 10.949 [95% CI: 3.262-36.747], p < 0.001), multifocal or multicentric lesions (OR, 2.467 [95% CI: 1.067-5.706], p = 0.035), segmental or regional distribution of NME (OR, 8.514 [95% CI: 1.049-69.098], p = 0.045) and rim enhancement of mass (OR, 4.261 [95% CI: 1.347-13.477], p = 0.014) were significantly associated with the discrepancy between MRI and pathology. Conclusion: Presence of DCIS, luminal B or HER2-enriched subtype, multicentric or multifocal lesions, segmental or regional distribution of NME and rim enhancement of mass may lead to a decrease in diagnostic accuracy of MRI in patients of breast cancer treated with NAC.

4.
Sci Rep ; 14(1): 12135, 2024 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802446

RESUMEN

To compare diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) parameters of single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI) in the differentiation of luminal vs. non-luminal breast cancer using histogram analysis. One hundred and sixty women with 111 luminal and 49 non-luminal breast lesions were enrolled in this study. All patients underwent ss-EPI and rs-EPI sequences on a 3.0T scanner. Histogram metrics were derived from mean kurtosis (MK), mean diffusion (MD) and the apparent diffusion coefficient (ADC) maps of two DWI sequences respectively. Student's t test or Mann-Whitney U test was performed for differentiating luminal subtype from non-luminal subtype. The ROC curves were plotted for evaluating the diagnostic performances of significant histogram metrics in differentiating luminal from non-luminal BC. The histogram metrics MKmean, MK50th, MK75th of luminal BC were significantly higher than those of non-luminal BC for both two DWI sequences (all P<0.05). Histogram metrics from rs-EPI sequence had better diagnostic performance in differentiating luminal from non-Luminal breast cancer compared to those from ss-EPI sequence. MK75th derived from rs-EPI sequence was the most valuable single metric (AUC, 0.891; sensitivity, 78.4%; specificity, 87.8%) for differentiating luminal from non-luminal BC among all the histogram metrics. Histogram metrics of MK derived from rs-EPI yielded better diagnostic performance for distinguishing luminal from non-luminal BC than that from ss-EPI. MK75th was the most valuable metric among all the histogram metrics.


Asunto(s)
Neoplasias de la Mama , Imagen de Difusión por Resonancia Magnética , Imagen Eco-Planar , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Imagen Eco-Planar/métodos , Persona de Mediana Edad , Adulto , Imagen de Difusión por Resonancia Magnética/métodos , Anciano , Diagnóstico Diferencial , Curva ROC
5.
Materials (Basel) ; 17(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38473599

RESUMEN

In salt lake areas, cast-in situ concrete structures are subjected to long-term corrosion by sulfate and magnesium ions. The properties of concrete can be improved by adding materials like basalt fiber (BF). To investigate the degradation process and mechanism of cast-in situ concrete with premixed BF under the dual corrosion of sulfate and magnesium salts, concrete with a content of BF ranging from 0 to 0.5% was prepared. Specimens were subjected to different internal and external corrosion conditions and immersed for 180 days. Dimension, mass, and appearance changes at different immersion times were recorded. The compressive and flexural strength of the specimens were tested and continually observed throughout the immersion time. Mineral and microstructural changes at different immersion times were determined by the XRD, TG, and SEM analysis methods. Results indicated that external sulfate-internal magnesium combined attack had a significant negative effect on the early strength. The compressive and flexural strength of the corroded specimens decreased by 17.2% and 14.1%, respectively, compared to the control group at 28 days. The premixed magnesium ions caused the decomposition of the C-S-H gel, resulting in severe spalling and lower mechanical properties after immersing for a long time. As the BF can inhibit crack development, the properties of the concrete premixed with BF were improved. Specimens exhibited superior performance at a BF content of 0.5%, resulting in a 16.2% increase in flexural strength. This paper serves as a valuable reference for the application of basalt fiber-reinforced concrete under the challenging conditions of sulfate-magnesium combined attack.

6.
J Phys Chem Lett ; 15(12): 3441-3449, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38511538

RESUMEN

The vulnerability of mixed halide perovskite nanocrystals (NCs) remains challenging because of the weak interaction between commonly employed ligands, oleic acid/oleylamine (OAm/OA) and halide anions, coupled with substantial surface phonon energy. Here, we introduce 3-aminopropyltriethoxysilane (APTES) as a capping ligand to modify CsPbBrI2 NCs to enhance the interactions between them. The optical properties have been significantly enhanced, and halide segregation has been suppressed, both of which can be attributed to the reduced phonon energy and exciton-phonon coupling strength. Moreover, these APTES-CsPbBrI2 NCs exhibit a broad color gamut and sustained color stability during long-term operation, indicating their promising potential in display technologies. This work may offer insights into surface engineering to enhance the properties and band stability of mixed halide perovskite NCs.

7.
ACS Appl Mater Interfaces ; 16(7): 9051-9059, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38348475

RESUMEN

The spontaneous centrosymmetry-breaking and robust room-temperature ferroelectricity in niobium oxide dihalides spurs a flurry of explorations into its promising second-order nonlinear optical properties, and promises potential applications in nonvolatile electro-optical and optoelectronic devices. However, the ambient stability of the niobium oxide dihalides remains questionable, which overshadows their future development. In this work, the chemical degradation of NbOI2 is comprehensively investigated using combined chemical and optical microscopies in conjunction with spectroscopies. We unveil the highly anisotropic degradation kinetics of NbOI2 driven by the hydrolysis process of the unstable dangling iodine bonds dominantly on the (010) facet and progressing along the c axis. Knowing its degradation mechanism, the NbOI2 flake can then be stabilized by the hexagonal boron nitride encapsulation, which isolates the air moisture. These findings provide direct insights into the ambient instability of NbOI2, and they deliver possible solutions to circumvent this issue, which are essential for its practical integration in photonic and electronic devices.

8.
Nat Commun ; 15(1): 1628, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388527

RESUMEN

Euglena gracilis, a model organism of the eukaryotic supergroup Discoba harbouring also clinically important parasitic species, possesses diverse metabolic strategies and an atypical electron transport chain. While structures of the electron transport chain complexes and supercomplexes of most other eukaryotic clades have been reported, no similar structure is currently available for Discoba, limiting the understandings of its core metabolism and leaving a gap in the evolutionary tree of eukaryotic bioenergetics. Here, we report high-resolution cryo-EM structures of Euglena's respirasome I + III2 + IV and supercomplex III2 + IV2. A previously unreported fatty acid synthesis domain locates on the tip of complex I's peripheral arm, providing a clear picture of its atypical subunit composition identified previously. Individual complexes are re-arranged in the respirasome to adapt to the non-uniform membrane curvature of the discoidal cristae. Furthermore, Euglena's conformationally rigid complex I is deactivated by restricting ubiquinone's access to its substrate tunnel. Our findings provide structural insights for therapeutic developments against euglenozoan parasite infections.


Asunto(s)
Euglena , Membranas Mitocondriales , Transporte de Electrón , Membranas Mitocondriales/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético
9.
Angew Chem Int Ed Engl ; 63(3): e202316154, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38058217

RESUMEN

Additive engineering has emerged as one of the most promising strategies to improve the performance of perovskite solar cells (PSCs). Among additives, perovskite nanocrystals (NCs) have a similar chemical composition and matched lattice structure with the perovskite matrix, which can effectively enhance the efficiency and stability of PSCs. However, relevant studies remain limited, and most of them focus on bromide-involved perovskite NCs, which may undergo dissolution and ion exchange within the FAPbI3 host, potentially resulting in an enlarged band gap. In this work, we employ butylamine-capped CsPbI3 NCs (BPNCs) as additives in PSCs, which can be well maintained and serve as seeds for regulating the crystallization and growth of perovskite films. The resultant perovskite film exhibits larger domain sizes and fewer grain boundaries without compromising the band gap. Moreover, BPNCs can alleviate lattice strain and reduce defect densities within the active layer. The PSCs incorporating BPNCs show a champion power conversion efficiency (PCE) of up to 25.41 %, well over both Control of 22.09 % and oleic acid/oleylamine capped CsPbI3 NC (PNC)-based devices of 23.11 %. This work illustrates the key role of nanosized seed surfaces in achieving high-performance photovoltaic devices.

10.
Nat Commun ; 14(1): 8254, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086809

RESUMEN

Recent progress in two-dimensional ferroelectrics greatly expands the versatility and tunability in van der Waals heterostructure based electronics. However, the switching endurance issue that widely plagues conventional ferroelectrics in practical applications is hitherto unexplored for van der Waals layered ferroelectrics. Herein, we report the observation of unusual polarization fatigue behaviors in van der Waals layered CuInP2S6, which also possesses finite ionic conductivity at room temperature. The strong intertwinement of the short-range polarization switching and long-range ionic movement in conjunction with the van der Waals layered structure gives rise to unique morphological and polarization evolutions under repetitive electric cycles. With the help of concerted chemical, structural, lattice vibrational and dielectric analyses, we unravel the critical role of the synergy of ionic migration and surface oxidation on the anomalous polarization enhancement and the eventual polarization degradation. This work provides a general insight into the polarization fatigue characteristics in ionically-active van der Waals ferroelectrics and delivers potential solutions for the realization of fatigue-free capacitors.

11.
Nat Commun ; 14(1): 2542, 2023 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-37248254

RESUMEN

Tetrahymena thermophila, a classic ciliate model organism, has been shown to possess tubular mitochondrial cristae and highly divergent electron transport chain involving four transmembrane protein complexes (I-IV). Here we report cryo-EM structures of its ~8 MDa megacomplex IV2 + (I + III2 + II)2, as well as a ~ 10.6 MDa megacomplex (IV2 + I + III2 + II)2 at lower resolution. In megacomplex IV2 + (I + III2 + II)2, each CIV2 protomer associates one copy of supercomplex I + III2 and one copy of CII, forming a half ring-shaped architecture that adapts to the membrane curvature of mitochondrial cristae. Megacomplex (IV2 + I + III2 + II)2 defines the relative position between neighbouring half rings and maintains the proximity between CIV2 and CIII2 cytochrome c binding sites. Our findings expand the current understanding of divergence in eukaryotic electron transport chain organization and how it is related to mitochondrial morphology.


Asunto(s)
Tetrahymena thermophila , Tetrahymena thermophila/genética , Membranas Mitocondriales/metabolismo , Mitocondrias/metabolismo
12.
Small ; 19(17): e2207312, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36725364

RESUMEN

All-inorganic lead halide perovskite nanocrystals (NCs) emerge as a rising star in photovoltaic fields on account of their excellent optoelectronic properties. However, it still remains challenging to further promote photovoltaic efficiency due to the susceptible surface and inevitable vacancies. Here, this work reports a 3D/2D core/shell perovskite heterojunction based on CsPbI3 NCs and its performance in solar cells. The guanidinium (GA+ ) rich 2D nanoshells can significantly passivate surface trap states and lower the capping ligand density, resulting in improved photoelectric properties and carrier transport and diminished nonradiative recombination centers via the hydrogen bonds from amino groups in GA+ ions. Consequently, an outstanding power conversion efficiency (PCE) of up to 15.53% is realized, substantially higher than the control device (13.77%). This work highlights the importance of surface chemistry and offers a feasible avenue to achieve high-performance perovskite NCs-based optoelectronic devices.

13.
Quant Imaging Med Surg ; 13(2): 735-746, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36819265

RESUMEN

Background: Histogram analysis of the diffusion-weighted imaging (DWI) parameters is widely used to differentiate the breast lesions. However, histogram analysis of the diffusion-kurtosis imaging (DKI) parameters for the single-shot echo-planar imaging (ss-EPI) and readout-segmented echo planar imaging (rs-EPI) sequences has not been compared in breast cancer. Thus, this study is to investigate the diagnostic accuracy and reliability of the histogram parameters derived from the rs-EPI and ss-EPI sequences of DKI parameters in distinguishing between the benign and malignant breast lesions. Methods: This single-center, retrospective cohort study enrolled 205 consecutive patients with breast lesions (65 benign and 140 malignant). The patients underwent breast magnetic resonance imaging (MRI) with a 3T scanner using the rs-EPI and ss-EPI sequences with 4 b values (0, 50, 1,000, and 2,000 s/mm2). The regions of interest (ROIs) were manually delineated for all the lesion images from both the sequences, and the histogram parameters were extracted from the apparent diffusion coefficient (ADC) and apparent diffusional kurtosis (Kapp) maps. Statistical analysis was performed using the Kolmogorov-Smirnov test, the student's t-test, and the receiver operating characteristic (ROC) curves. Results: The mean, 25th, 50th, 75th, and 100th percentiles, skewness, and kurtosis values derived from apparent diffusion for non-Gaussian distribution (Dapp) and Kapp maps showed good or excellent intra-observer agreement (ICC: 0.695 to 0.863).The mean and the 25th, 50th, 75th, and 100th percentile values for Dapp were significantly lower and the mean and the 25th, 50th, 75th, and 100th percentile values for Kapp were significantly higher in the malignant breast lesions compared with those in the benign breast lesions for both the rs-EPI and ss-EPI sequences (all P<0.05). The majority of the histogram Kapp and Dapp parameters (except skewness and kurtosis) for the benign and malignant lesions showed significant differences between the ss-EPI and the rs-EPI sequences (P<0.05). ROC curve analysis showed that the AUC values for the 75th percentile of Kapp (0.854 for rs-EPI, 0.844 for ss-EPI) and the 25th percentile of Dapp (0.866 for rs-EPI, 0.858 for ss-EPI) were highest for both DKI sequences. The diagnostic performance of the rs-EPI sequence was better than the ss-EPI sequence for all the histogram parameters except the skewness value of Dapp. Conclusions: Histogram parameters from the rs-EPI sequence were more reliable and accurate in differentiating malignant and benign breast lesions than those from the ss-EPI sequence.

14.
J Magn Reson Imaging ; 58(6): 1725-1736, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36807457

RESUMEN

BACKGROUND: The recommended technique for breast diffusion-weighted imaging (DWI) acquisitions is not sufficiently standardized in clinical practice. PURPOSE: To investigate the intraobserver and interobserver reproducibility of DWI measurements, diffusion-kurtosis imaging (DKI) parameters, and image quality evaluation in breast lesions between single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI). STUDY TYPE: Prospective. POPULATION: A total of 295 women with 209 malignant and 86 benign breast lesions. FIELD STRENGTH/SEQUENCE: A 3-T; fat-saturated T2-weighted MR imaging (T2WI); multi-b-value DWI with both ss-EPI and rs-EPI readouts; T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). ASSESSMENT: Mean kurtosis (MK), mean diffusion (MD), and apparent diffusion coefficient (ADC) values were measured for each lesion on ss-EPI and rs-EPI, respectively. Image quality was visually evaluated regarding image sharpness, geometric distortion, lesion conspicuity, visualization of anatomic structures, and overall quality. Quantitative and qualitative analyses were performed twice with a time interval of 2 weeks. STATISTICAL TESTS: Intraobserver and interobserver reproducibility were evaluated using intra-class correlation coefficients (ICC), within-subject coefficient of variation (wCV), and Bland-Altman plots. RESULTS: MK, MD, and ADC quantitative parameters for breast lesions showed excellent intraobserver and interobserver reproducibility, with ICCs >0.75 and wCV values ranging from 2.51% to 7.08% for both sequences. The wCV values in both intraobserver and interobserver measurements were higher in the ss-EPI sequence (3.63%-7.08%) than that of the rs-EPI sequence (2.51%-3.62%). The wCV values differed in subgroups with different histopathological types of lesions, breast density, lesion morphology, and lesion sizes, respectively. Furthermore, rs-EPI (ICCs, 0.76-0.97; wCV values, 2.41%-6.04%) had better intraobserver and interobserver reproducibility than ss-EPI (ICCs, 0.54-0.90; wCV values, 6.18%-13.69%) with regard to image quality. DATA CONCLUSION: Compared to the ss-EPI, the rs-EPI sequence showed higher intraobserver and interobserver reproducibility for quantitative diffusion-related parameters and image quality assessments measured in breast DWI and DKI. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Imagen Eco-Planar , Humanos , Femenino , Imagen Eco-Planar/métodos , Reproducibilidad de los Resultados , Estudios Prospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora
15.
Front Oncol ; 12: 940655, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338691

RESUMEN

Purpose: To develop a nomogram based on radiomics signature and deep-learning signature for predicting the axillary lymph node (ALN) metastasis in breast cancer. Methods: A total of 151 patients were assigned to a training cohort (n = 106) and a test cohort (n = 45) in this study. Radiomics features were extracted from DCE-MRI images, and deep-learning features were extracted by VGG-16 algorithm. Seven machine learning models were built using the selected features to evaluate the predictive value of radiomics or deep-learning features for the ALN metastasis in breast cancer. A nomogram was then constructed based on the multivariate logistic regression model incorporating radiomics signature, deep-learning signature, and clinical risk factors. Results: Five radiomics features and two deep-learning features were selected for machine learning model construction. In the test cohort, the AUC was above 0.80 for most of the radiomics models except DecisionTree and ExtraTrees. In addition, the K-nearest neighbor (KNN), XGBoost, and LightGBM models using deep-learning features had AUCs above 0.80 in the test cohort. The nomogram, which incorporated the radiomics signature, deep-learning signature, and MRI-reported LN status, showed good calibration and performance with the AUC of 0.90 (0.85-0.96) in the training cohort and 0.90 (0.80-0.99) in the test cohort. The DCA showed that the nomogram could offer more net benefit than radiomics signature or deep-learning signature. Conclusions: Both radiomics and deep-learning features are diagnostic for predicting ALN metastasis in breast cancer. The nomogram incorporating radiomics and deep-learning signatures can achieve better prediction performance than every signature used alone.

16.
ACS Appl Mater Interfaces ; 14(35): 40126-40135, 2022 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-36000928

RESUMEN

Transition metal thiophosphate, CuInP2S6 (CIPS), has recently emerged as a potentially promising material for photoelectrochemical (PEC) water splitting due to its intrinsic ferroelectric polarization for spontaneous photocarrier separation. However, the poor kinetics of the hydrogen evolution reaction (HER) greatly limits its practical applications. Herein, we report self-enhancing photocatalytic behavior of a CIPS photocathode due to chemically driven oxygen incorporation by photoassisted acid oxidation. The optimal oxygen-doped CIPS demonstrates a >1 order of magnitude enhancement in the photocurrent density compared to that of pristine CIPS. Through comprehensive spectroscopic and microscopic investigations combined with theoretical calculations, we disclose that oxygen doping will lower the Fermi level position and decrease the HER barrier, which further accelerates charge separation and improves the HER activity. This work may deliver a universal and facile strategy for improving the PEC performance of other van der Waals metal thiophosphates.

17.
Neurosci Bull ; 38(9): 1007-1024, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35235180

RESUMEN

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na+-K+-Cl- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTENflox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Malformaciones del Desarrollo Cortical , Animales , Epilepsia Refractaria/cirugía , Epilepsia/patología , Malformaciones del Desarrollo Cortical/patología , Malformaciones del Desarrollo Cortical de Grupo I , Ratones , Neuronas/patología , Convulsiones/patología
18.
Acad Radiol ; 29 Suppl 1: S107-S115, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33712393

RESUMEN

RATIONALE AND OBJECTIVES: Intra-peritumoural textural transition (Ipris) is a new radiomics method, which includes a series of quantitative measurements of the image features that represent the differences between the inside and outside of the tumour. This study aimed to explore the feasibility of Ipris analysis for the preoperative prediction of axillary lymph node (ALN) status in patients with breast cancer based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: This study was approved by the Institutional Review Board (IRB) of our hospital. One hundred sixty-six patients with clinicopathologically confirmed invasive breast cancer and ALN status were enrolled. All patients underwent preoperative breast DCE-MRI examinations. The primary breast lesion was manually segmented using the ITK-SNAP software for each patient. Two sets of image features were extracted, including Ipris features and conventional intratumoural features. Feature selection was conducted using Spearman correlation analysis and support vector machine with recursive feature elimination (SVM-RFE). Next, three models were established in training dataset: Model 1 was established by Ipris features; Model 2 was established by intratumoural features; Model 3 was established by combining Ipris features and intratumoural features. The performances of the three models were evaluated for the prediction of ALN status in testing datasets. RESULTS: Model 1 with four Ipris features achieved an AUC of 0.816 (95% CI, 0.733-0.883) and 0.829 (95% CI, 0.695-0.922) in the training and testing datasets, respectively. Model 2 with six intratumoural features achieved an AUC of 0.801 (95% CI, 0.716-0.870) and 0.824 (95% CI, 0.689-0.918) in the training and testing datasets, respectively. By incorporating the Ipris and intratumoural features, the AUC of Model 3 increased to 0.968 (95% CI, 0.916-0.992) and 0.855 (95% CI, 0.724-0.939) in the training and testing datasets, respectively. CONCLUSION: Ipris features based on DCE-MRI can be used to predict ALN status in patients with breast cancer. The model combining intratumoural and Ipris features achieved higher prediction performance.


Asunto(s)
Neoplasias de la Mama , Axila/diagnóstico por imagen , Axila/patología , Mama/patología , Neoplasias de la Mama/patología , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
19.
IEEE Trans Pattern Anal Mach Intell ; 44(10): 6782-6794, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34232866

RESUMEN

AutoML aims at best configuring learning systems automatically. It contains core subtasks of algorithm selection and hyper-parameter tuning. Previous approaches considered searching in the joint hyper-parameter space of all algorithms, which forms a huge but redundant space and causes an inefficient search. We tackle this issue in a cascaded algorithm selection way, which contains an upper-level process of algorithm selection and a lower-level process of hyper-parameter tuning for algorithms. While the lower-level process employs an anytime tuning approach, the upper-level process is naturally formulated as a multi-armed bandit, deciding which algorithm should be allocated one more piece of time for the lower-level tuning. To achieve the goal of finding the best configuration, we propose the Extreme-Region Upper Confidence Bound (ER-UCB) strategy. Unlike UCB bandits that maximize the mean of feedback distribution, ER-UCB maximizes the extreme-region of feedback distribution. We first consider stationary distributions and propose the ER-UCB-S algorithm that has O(Klnn) regret upper bound with K arms and n trials. We then extend to non-stationary settings and propose the ER-UCB-N algorithm that has O(Knν) regret upper bound, where [Formula: see text]. Finally, empirical studies on synthetic and AutoML tasks verify the effectiveness of ER-UCB-S/N by their outperformance in corresponding settings.

20.
J Phys Condens Matter ; 33(35)2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-34153953

RESUMEN

Visible-light-active ferroelectric materials are gaining increasing attention due to the unique ferroelectric photovoltaic effect. To boost the light harvesting capability, vast research is devoted to band gap engineering by chemical substitutions, regardless of the side effect on ferroelectric polarization. Here, we focus on how polar order affects the optical and photovoltaic properties. Using BiFeO3as the model system, we induce the polarization rotation by A-site La substitution, which results in continuous reduction of optical anisotropy of the samples, as revealed by the concerted optical characterizations. This further causes the decrease of angular dependence of ferroelectric photovoltaic effect on the light polarization. The results demonstrate the inner connection of the ferroelectric polarization and optical anisotropy via the lattice degree of freedom.

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