RESUMEN

OBJECTIVES: To develop and validate imaging-based models for predicting the malignancy risk of intraductal papillary mucinous neoplasm (IPMN). MATERIALS AND METHODS: We retrospectively analyzed data from 241 IPMN patients who underwent preoperative CT and MRI for model development. Cyst size, presence and size of the enhancing mural nodule (EMN), main pancreatic duct (MPD) diameter, thickened/enhancing cyst wall, abrupt MPD caliber change with distal atrophy, and lymphadenopathy were assessed. Multiple logistic regression models predicting malignancy risk were created using either continuous (Model C) or dichotomized variables (Model D) using these imaging features. Validation included internal (n = 55) and external (n = 43) datasets. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and compared with that of the international guideline-based model (Model F). RESULTS: Model C identified age, EMN size, MPD diameter, and lymphadenopathy as independent predictors on CT, and age and presence and size of EMN on MRI. Model D identified age ≥ 68, cyst size ≥ 31 mm, EMN ≥ 6 mm, MPD ≥ 7 mm, and lymphadenopathy as independent predictors on CT, and age ≥ 68, EMN ≥ 4.5 mm, and lymphadenopathy on MRI. Model C (AUC, 0.763-0.899) performed slightly better than Model D (AUC, 0.753-0.912) without statistical significance. No significant difference was observed between Models C and F (AUC, 0.729-0.952). Combining Model C with obstructive jaundice improved performance (AUC, 0.802-0.941) without statistical significance. CONCLUSION: Our imaging-based models effectively predicted the malignancy risk of IPMNs, comparable to international consensus guidelines. CLINICAL RELEVANCE STATEMENT: Imaging features are important for predicting the malignant potential of IPMNs. Our imaging-based model may help determine surgical candidacy for patients with IPMNs. KEY POINTS: Non-invasively determining the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) allows for appropriate treatment decision-making We identified multiple imaging features that are associated with malignant transformation and developed models for this prediction. Our model performs comparably with international consensus guidelines in predicting the malignant potential of IPMNs.

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De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice. Unexpectedly, these DEPs, in conjunction with previously identified CYFIP2 brain interactors, included not only other WRC components but also numerous proteins associated with membraneless organelles (MLOs) involved in mRNA processing and translation within cells, including the nucleolus, stress granules, and processing bodies. Additionally, single-cell transcriptomic analysis of the Cyfip2 knock-out forebrain revealed gene expression changes linked to cellular stress responses and MLOs. We also observed morphological changes in MLOs in Cyfip2 knock-out brains and CYFIP2 knock-down cells under basal and stress conditions. Lastly, we demonstrated that CYFIP2 knock-down in cells, potentially through WRC-dependent actin regulation, suppressed the phosphorylation levels of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), thereby enhancing protein synthesis. These results suggest a physical and functional connection between CYFIP2 and various MLO proteins and also extend CYFIP2's role within the WRC from actin regulation to influencing eIF2α phosphorylation and protein synthesis. With these dual functions, CYFIP2 may fine-tune the balance between MLO formation/dynamics and protein synthesis, a crucial aspect of proper mRNA processing and translation.

RESUMEN

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.

Asunto(s)

Trastorno del Espectro Autista , Cilios , Epéndimo , Ratones Noqueados , Fenotipo , Animales , Masculino , Ratones , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/fisiopatología , Conducta Animal , Cilios/metabolismo , Modelos Animales de Enfermedad , Epéndimo/metabolismo , Hipocampo/metabolismo , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patología , Hidrocefalia/fisiopatología , Katanina/metabolismo , Katanina/genética , Ratones Endogámicos C57BL , Neuronas/metabolismo , Sinapsis/metabolismo , Transcriptoma/genética

RESUMEN

The slow photon effect in inverse opal photonic crystals represents a promising approach to manipulate the interactions between light and matter through the design of material structures. This study introduces a novel ordered inverse opal photonic crystal (IOPC) sensitized with perovskite quantum dots (PQDs), demonstrating its efficacy for efficient visible-light-driven H2 generation via water splitting. The rational structural design contributes to enhanced light harvesting. The sensitization of the IOPC with PQDs improves optical response performance and enhances photocatalytic H2 generation under visible light irradiation compared to the IOPC alone. The designed photoanode exhibits a photocurrent density of 3.42 mA cm-2 at 1.23 V vs RHE. This work advances the rational design of visible light-responsive photocatalytic heterostructure materials based on wide band gap metal oxides for photoelectrochemical applications.

RESUMEN

PURPOSE: To investigate the common CT findings of high-grade (HG) PanIN and clinical effects in the remnant pancreas in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. MATERIALS AND METHODS: Two hundred fifty-one patients with surgically confirmed IPMNs (118 malignant [invasive carcinoma/high-grade dysplasia] and 133 benign [low-grade dysplasia]) were retrospectively enrolled. The grade of PanIN (233 absent/low-grade and 18 high-grade) was recorded, and all patients underwent serial CT follow-up before and after surgery. Two radiologists analyzed CT findings of high-risk stigmata or worrisome features according to 2017 international consensus guidelines. They also analyzed tumor recurrence on serial follow-up CT after surgery. Statistical analyses were performed to identify significant predictors and clinical impact on postoperative outcomes of HG PanIN. RESULTS: PanIN grade showed a significant association with IPMN grade (p = 0.012). Enhancing mural nodules ≥5 mm, abrupt main pancreatic duct (MPD) changes with distal pancreatic atrophy, increased mural nodule size and MPD diameter were common findings in HG PanIN (P<0.05). In multivariate analysis, abrupt MPD change with distal pancreatic atrophy (odds ratio (OR) 6.59, 95% CI: 2.32-18.72, <0.001) and mural nodule size (OR, 1.05; 95% CI, 1.02-1.08, 0.004) were important predictors for HG PanIN. During postoperative follow-up, HG PanIN (OR, 4.98; 95% CI, 1.22-20.33, 0.025) was significantly associated with cancer recurrence in the remnant pancreas. CONCLUSION: CT can be useful for predicting HG PanIN using common features, such as abrupt MPD changes and mural nodules. In HG PanIN, extra caution is needed to monitor postoperative recurrence during follow-up.

Asunto(s)

Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Clasificación del Tumor , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Adulto , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma in Situ/patología , Carcinoma in Situ/diagnóstico por imagen , Carcinoma in Situ/cirugía

RESUMEN

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.

Asunto(s)

Carcinoma Hepatocelular , Fluorocarburos , Neoplasias Hepáticas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Estudios Prospectivos , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Sensibilidad y Especificidad , Ultrasonografía/métodos

RESUMEN

Fe-based nanostructures have possessed promising properties that make it suitable for chiral sensing and imaging applications owing to their ultra-small size, non-toxicity, biocompatibility, excellent photostability, tunable fluorescence, and water solubility. This review summarizes the recent research progress in the field of Fe-based nanostructures and places special emphases on their applications in chiral sensing and imaging. The synthetic strategies to prepare the targeted Fe-based structures were also introduced. The chiral sensing and imaging applications of the nanostructures are discussed in details.

Asunto(s)

Nanoestructuras , Puntos Cuánticos , Humanos , Puntos Cuánticos/química , Nanoestructuras/química , Diagnóstico por Imagen , Fluorescencia , Solubilidad

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BACKGROUND: Whether deep learning-based CT reconstruction could improve lesion conspicuity on abdominal CT when the radiation dose is reduced is controversial. OBJECTIVES: To determine whether DLIR can provide better image quality and reduce radiation dose in contrast-enhanced abdominal CT compared with the second generation of adaptive statistical iterative reconstruction (ASiR-V). AIMS: This study aims to determine whether deep-learning image reconstruction (DLIR) can improve image quality. METHOD: In this retrospective study, a total of 102 patients were included, who underwent abdominal CT using a DLIR-equipped 256-row scanner and routine CT of the same protocol on the same vendor's 64-row scanner within four months. The CT data from the 256-row scanner were reconstructed into ASiR-V with three blending levels (AV30, AV60, and AV100), and DLIR images with three strength levels (DLIR-L, DLIR-M, and DLIR-H). The routine CT data were reconstructed into AV30, AV60, and AV100. The contrast-to-noise ratio (CNR) of the liver, overall image quality, subjective noise, lesion conspicuity, and plasticity in the portal venous phase (PVP) of ASiR-V from both scanners and DLIR were compared. RESULTS: The mean effective radiation dose of PVP of the 256-row scanner was significantly lower than that of the routine CT (6.3±2.0 mSv vs. 2.4±0.6 mSv; p< 0.001). The mean CNR, image quality, subjective noise, and lesion conspicuity of ASiR-V images of the 256-row scanner were significantly lower than those of ASiR-V images at the same blending factor of routine CT, but significantly improved with DLIR algorithms. DLIR-H showed higher CNR, better image quality, and subjective noise than AV30 from routine CT, whereas plasticity was significantly better for AV30. CONCLUSION: DLIR can be used for improving image quality and reducing radiation dose in abdominal CT, compared with ASIR-V.

Asunto(s)

Aprendizaje Profundo , Humanos , Mejoramiento de la Calidad , Estudios Retrospectivos , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Procesamiento de Imagen Asistido por Computador

RESUMEN

Aberrant regulation of the long non-coding RNA SRY-box transcription factor 2 overlapping transcript (SOX2OT) has been reported in various diseases including gastric cancer (GC). However, an association between the well-studied rs9839776 single nucleotide polymorphism in SOX2OT and GC susceptibility has not been reported. This study aimed to evaluate the association between the rs9839776 single nucleotide polymorphism in SOX2OT and GC risk. Genotyping of rs9839776 was conducted using TaqMan genotyping assay for 460 patients with GC and 386 controls. We found that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased GC risk (P = .046, adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.52-1.00 and P = .044, AOR = 0.74, 95% CI = 0.56-0.99, respectively). In addition, stratified analysis revealed that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased risk of lymph node metastasis-negative (P = .039, AOR = 0.67, 95% CI = 0.46-0.98 and P = .049, AOR = 0.71, 95% CI = 0.51-1.00, respectively) and tumor stage I (A+B)/II (A+B+C) (P = .028, AOR = 0.66, 95% CI = 0.50-0.96 and P = .041, AOR = 0.71, 95% CI = 0.52-0.99, respectively) GC. Our findings suggest that the rs9839776 T allele may be a protective factor against GC susceptibility. Further research is needed to clarify whether rs9839776 affects SOX2OT expression.

Asunto(s)

ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Factores Protectores , República de Corea , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/patología

RESUMEN

OBJECTIVE: To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA). MATERIALS AND METHODS: This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020. Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ). RESULTS: No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all). The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754-0.841] vs. 0.753 [0.697-0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884). CONCLUSION: CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.

Asunto(s)

Neoplasias de los Conductos Biliares , Colangiocarcinoma , Masculino , Humanos , Pancreatocolangiografía por Resonancia Magnética/métodos , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Medios de Contraste , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos

RESUMEN

Dopamine (DA) neurons in the ventral tegmental area (VTA) promote social brain functions by releasing DA onto nucleus accumbens neurons, but it remains unclear how VTA neurons communicate with cortical neurons. Here, we report that the medial prefrontal cortex (mPFC)-lateral hypothalamus (LH)-VTA pathway contributes to social deficits in mice with IRSp53 deletion restricted to cortical excitatory neurons (Emx1-Cre;Irsp53fl/fl mice). LH-projecting mutant mPFC neurons display abnormally increased excitability involving decreased potassium channel gene expression, leading to excessive excitatory synaptic input to LH-GABA neurons. A circuit-specific IRSp53 deletion in LH-projecting mPFC neurons also increases neuronal excitability and induces social deficits. LH-GABA neurons with excessive mPFC excitatory synaptic input show a compensatory decrease in excitability, weakening the inhibitory LHGABA-VTAGABA pathway and subsequently over-activating VTA-GABA neurons and over-inhibiting VTA-DA neurons. Accordingly, optogenetic activation of the LHGABA-VTAGABA pathway improves social deficits in Emx1-Cre;Irsp53fl/fl mice. Therefore, the mPFC-LHGABA-VTAGABA-VTADA pathway contributes to the social deficits in Emx1-Cre;Irsp53fl/fl mice.

Asunto(s)

Área Hipotalámica Lateral , Área Tegmental Ventral , Animales , Ratones , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Área Hipotalámica Lateral/metabolismo , Núcleo Accumbens/metabolismo , Área Tegmental Ventral/metabolismo

RESUMEN

OBJECTIVE: The aim of the work described here was to evaluate the diagnostic performance of perfluorobutane (PFB)-enhanced ultrasound in differentiating hepatocellular carcinoma (HCC) from non-HCC malignancies and other benign lesions using different acquisition methods. METHODS: This prospective study included 69 patients with solid liver lesions larger than 1 cm who were scheduled for biopsy or radiofrequency ablation between September 2020 and March 2021. Lesion diagnosis was designated by three blinded radiologists after reviewing three different sets of acquired images selected according to the following presumed acquisition methods: (i) method A, acquisition up to 5 min after contrast injection; (ii) method B, acquisition up to 1 min after contrast injection with additional Kupffer phase; and (iii) method C, acquisition up to 5 min after contrast injection with additional Kupffer phase. RESULTS: After excluding 7 technical failures, 62 patients with liver lesions (mean size: 24.2 ± 14.8 mm), which consisted of 7 benign lesions, 37 non-HCC malignancies and 18 HCCs. For the HCC diagnosis, method C had the highest sensitivity (75.9%), followed by method B (72.2%) and method A (68.5%), but failed to exhibit statistical significance (p = 0.12). There was no significant difference with respect to the pooled specificity between the three methods (p = 0.28). Diagnostic accuracy was the highest with method C (87.1%) but failed to exhibit statistical significance (p = 0.24). CONCLUSION: Image acquisition up to 5 min after contrast injection with additional Kupffer phase could potentially result in high accuracy and sensitivity without loss of specificity in diagnosing HCC with PFB-enhanced ultrasound.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Prospectivos , Medios de Contraste , Ultrasonografía/métodos , Imagen por Resonancia Magnética/métodos , Sensibilidad y Especificidad , Estudios Retrospectivos

RESUMEN

The rational synthesis and tailoring of metal-organic frameworks (MOFs) with multifunctional micro/nanoarchitectures have emerged as a subject of significant academic interest owing to their promising potential for utilization in advanced energy storage devices. Herein, we explored a category of three-dimensional (3D) NiCo2S4 nanospikes that have been integrated into a 1D Fe3C microarchitecture using a chemical surface transformation process. The resulting electrode materials, i.e., Fe3C@NiCo2S4 nanospikes, exhibit immense potential for utilization in high-performance hybrid supercapacitors. The nanospikes exhibit an elevated specific capacity (1894.2 F g-1 at 1 A g-1), enhanced rate capability (59%), and exceptional cycling stability (92.5% with 98.7% Coulombic efficiency) via a charge storage mechanism reminiscent of a battery. The augmented charge storage characteristics are attributed to the collaborative features of the active constituents, amplified availability of active sites inherent in the nanospikes, and the proficient redox chemical reactions of multi-metallic guest species. When using nitrogen-doped carbon nanofibers as the anode to fabricate hybrid supercapacitors, the device exhibits high energy and power densities of 62.98 Wh kg-1 and 6834 W kg-1, respectively, and shows excellent long-term cycling stability (95.4% after 5000 cycles), which affirms the significant potential of the proposed design for applications in hybrid supercapacitors. The DFT study showed the strong coupling of the oxygen from the electrolyte OH- with the metal atom of the nanostructures, resulting in high adsorption properties that facilitate the redox reaction kinetics.

RESUMEN

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

RESUMEN

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

Asunto(s)

Epilepsia , Canales de Potasio KCNQ , Animales , Ratones , Epilepsia/metabolismo , Canales de Potasio KCNQ/genética , Canal de Potasio KCNQ2/genética , Canal de Potasio KCNQ2/metabolismo , Canal de Potasio KCNQ3/metabolismo , Neuronas/metabolismo , Convulsiones/genética , Convulsiones/metabolismo

RESUMEN

ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIα and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIα inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIα hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles.

Asunto(s)

Trastorno Autístico , Discapacidad Intelectual , Ratones , Animales , Proteínas del Tejido Nervioso/metabolismo , Plasticidad Neuronal/genética , Potenciación a Largo Plazo/genética , Trastorno Autístico/metabolismo , Cognición , Proteínas de Homeodominio/metabolismo

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that are among the most appealing candidates for regenerative medicine and may aid in the repair and regeneration of skeletal disorders through multiple mechanisms, including angiogenesis, differentiation, and response to inflammatory conditions. Tauroursodeoxycholic acid (TUDCA) has recently been used in various cell types as one of these drugs. The mechanism of osteogenic differentiation by TUDCA in hMSCs remains unknown. METHODS: Cell proliferation was performed by the WST-1 method, and alkaline phosphatase activity and alizarin red-sulfate staining were used to confirm the osteogenic differentiation indicator. Expression of genes related to bone differentiation and specific genes related to signaling pathways was confirmed by quantitative real-time polymerase chain reaction. RESULTS: We found that cell proliferation was higher as the concentration increased, and showed that the induction of osteogenic differentiation was significantly enhanced. We also show that osteogenic differentiation genes were upregulated, with the expression of the epidermal growth factor receptor (EGFR) and cAMP responsive element binding protein 1 (CREB1) being specifically high. To confirm the participation of the EGFR signaling pathway, the osteogenic differentiation index and expression of osteogenic differentiation genes were determined after using an EGFR inhibitor. As a result, EGFR expression was remarkably low, and that of CREB1, cyclin D1, and cyclin E1 was also significantly low. CONCLUSIONS: Therefore, we suggest that TUDCA-induced osteogenic differentiation of human MSCs is enhanced through the EGFR/p-Akt/CREB1 pathway.

Asunto(s)

Células Madre Mesenquimatosas , Osteogénesis , Humanos , Osteogénesis/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diferenciación Celular/genética , Receptores ErbB/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo

RESUMEN

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiología , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Ultrasonografía/métodos , Medios de Contraste , República de Corea