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Abstract Currently, surgical resection remains the primary approach for treating oral squamous cell carcinoma (OSCC), with limited options for effective drug therapy. Cardamonin, a principal compound derived from Myristica fragrans of the Zingiberaceae family, has garnered attention for its potential to suppress the onset and progression of various malignancies encompassing breast cancer, hepatocellular carcinoma, and ovarian cancers. Nevertheless, the involvement of cardamonin in the treatment of OSCC and its underlying mechanisms are yet to be elucidated. This research explored the possible target of cardamonin in treating OSCC via network pharmacological analysis. Subsequently, this research investigated the impact of cardamonin on OSCC cells via in vitro experiments, revealing its capacity to impede the migration, proliferation, and invasion of OSCC cells. Additionally, western blotting analysis demonstrated that cardamonin facilitates apoptosis by regulating the PI3K/AKT pathway. The findings suggest that MMP9 and the PI3K/AKT signaling pathway may serve as the target and pathway of cardamonin in treating OSCC. To summarize, the research findings suggest that cardamonin may facilitate apoptosis in OSCC cells by inhibition of PI3K/AKT pathway activation. These outcomes offer a theoretical basis for the utilization of cardamonin as a natural drug for treating OSCC.

Abstract This study introduces a novel self-supervised learning method for single-frame subtraction and vessel segmentation in coronary angiography, addressing the scarcity of annotated medical samples in AI applications. We pretrain a U-Net model on a large dataset of unannotated coronary angiograms using an image-to-image translation framework, then fine-tune it on a limited set of manually annotated samples. The pretrained model excels at comprehensive single-frame subtraction, outperforming existing DSA methods. Fine-tuning with just 40 samples yields a Dice coefficient of 0.828 for vessel segmentation. On the public XCAD dataset, our model sets a new state-of-the-art benchmark with a Dice coefficient of 0.755, surpassing both unsupervised and supervised learning approaches. This method achieves robust single-frame subtraction and demonstrates that combining pretraining with minimal fine-tuning enables accurate coronary vessel segmentation with limited manual annotations. We successfully apply this approach to assist physicians in visualizing potential vascular stenosis sites during coronary angiography. Code, dataset, and a live demo will be available available at: https://github.com/newfyu/DeepSA .

Abstract The primary aim of this investigation was to leverage radiomics features derived from contrast-enhanced abdominal computed tomography (CT) scans to devise a predictive model to discern the benign and malignant nature of intraductal papillary mucinous neoplasms (IPMNs). Radiomic signatures were meticulously crafted to delineate benign from malignant IPMNs by extracting pertinent features from contrast-enhanced CT images within a designated training cohort (n = 84). Subsequent validation was conducted with data from an independent test cohort (n = 37). The discriminative ability of the model was quantitatively evaluated through receiver operating characteristic (ROC) curve analysis, with the integration of carefully selected clinical features to improve the comparative analysis. Arterial-phase images were utilized to construct a model comprising 8 features for distinguishing between benign and malignant cases. The model achieved an accuracy of 0.891 [95% confidence interval (95% CI), 0.816–0.996] in the cross-validation set and 0.553 (95% CI 0.360–0.745) in the test set. Conversely, employing 9 features from the venous-phase resulted in a model with a cross-validation accuracy of 0.862 (95%CI 0.777–0.946) and a test set accuracy of 0.801 (95% CI 0.653–0.950).Integrating the identified clinical features with imaging features yielded a model with a cross-validation accuracy of 0.934 (95% CI 0.879–0.990) and a test set accuracy of 0.904 (95% CI 0.808–0.999), thereby further improving its discriminatory ability. Our findings distinctly illustrate that venous-phase radiomics features eclipse arterial-phase radiomic features in terms of predictive accuracy regarding the nature of IPMNs. Furthermore, the synthesis and meticulous screening of clinical features with radiomic data significantly increased the diagnostic efficacy of our model, underscoring the pivotal importance of a comprehensive and integrated approach for accurate risk stratification in IPMN management.

Abstract Reticulocalbin 1 (RCN1), a calcium-binding protein located in the endoplasmic reticulum (ER) lumen, contains six conserved regions. Its main functions include maintaining intracellular homeostasis and regulating cell proliferation and apoptosis, and it plays an important role in the development of various tumours. However, the exact function of RCN1 in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the aim of this study was to investigate the effects of RCN1 on the biological behaviour of OSCC and the regulation of tumour-associated macrophage (TAM) polarization. The expression of RCN1 in OSCC and normal oral mucosa was evaluated through bioinformatics analysis and immunohistochemical staining. The growth, migration, and invasion of OSCC cells were observed after knockdown of RCN1 using CCK-8 and Transwell assays. Apoptosis was detected by flow cytometry. The effect of tumour cell-derived RCN1 on the polarization of THP-1 macrophages was investigated by establishing a coculture model of THP-1 macrophages and OSCC cells. Additionally, changes in the expression levels of relevant proteins were detected using Western blotting. The upregulation of RCN1 in tumour tissues compared to normal oral mucosal tissues is associated with a poor prognosis and can be utilized as a prognostic indicator for OSCC. Knockdown of RCN1 inhibited the proliferation, migration, and invasion of OSCC cells. Additionally, knockdown of RCN1 in Cal-27 and SCC-25 cells resulted in inhibition of the M2 polarization of THP-1 macrophages. RCN1 knockdown inhibits OSCC progression and M2 macrophage polarization. Targeting RCN1 may be a promising approach for OSCC treatment.

Abstract This study aimed to evaluate the performance of traditional-deep learning combination model based on Doppler ultrasound for diagnosing malignant complex cystic and solid breast nodules. A conventional statistical prediction model based on the ultrasound features and basic clinical information was established. A deep learning prediction model was used to train the training group images and derive the deep learning prediction model. The two models were validated, and their accuracy rates were compared using the data and images of the test group, respectively. A logistic regression method was used to combine the two models to derive a combination diagnostic model and validate it in the test group. The diagnostic performance of each model was represented by the receiver operating characteristic curve and the area under the curve. In the test cohort, the diagnostic efficacy of the deep learning model was better than traditional statistical model, and the combined diagnostic model was better and outperformed the other two models (combination model vs traditional statistical model: AUC: 0.95 > 0.70, P = 0.001; combination model vs deep learning model: AUC: 0.95 > 0.87, P = 0.04). A combination model based on deep learning and ultrasound features has good diagnostic value.

Abstract Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges’ g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges’ g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges’ g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges’ g = − 0.795; 95% CI = − 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges’ g = 0.182; 95% CI = − 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.

Although proper tongue development is relevant to other structures in the craniofacial region, the molecular details of muscle development in tongue remain poorly understood. Here, we report that pregnant mice treated with retinoic acid (+RA) produce embryos with tongue malformation and a cleft palate. Histological analyses revealed that at E14.5, the tongues of +RA fetuses failed to descend and flatten. Ultrastructural analysis showed that at perinatal stage E18.5, the myofilaments failed to form normal structures of sarcomeres, and arranged disorderly in the genioglossus. The proliferation and levels of myogenic determination markers (Myf5 and MyoD) and myosin in the genioglossus were profoundly reduced. Wnt5a and Camk2d expressions were down-regulated, while levels of Tbx1, Ror2, and PKCδ were up-regulated in the tongues of +RA fetuses. In mock- and Wnt5a-transfected C2C12 (Wnt5a-C2C12) cells, Wnt5a overexpression impaired proliferation, and maintained Myf5 at a relative high level after RA treatment. Furthermore, Wnt5a overexpression positively correlated with levels of Camk2d and Ror2 in C2C12 cells after RA exposure. These data support the hypothesis that the Wnt5a/CaMKII pathway is directly involved in RA-induced hypoplasia and disorder of tongue muscles. [ABSTRACT FROM AUTHOR]

This study introduces a novel self-supervised learning method for single-frame subtraction and vessel segmentation in coronary angiography, addressing the scarcity of annotated medical samples in AI applications. We pretrain a U-Net model on a large dataset of unannotated coronary angiograms using an image-to-image translation framework, then fine-tune it on a limited set of manually annotated samples. The pretrained model excels at comprehensive single-frame subtraction, outperforming existing DSA methods. Fine-tuning with just 40 samples yields a Dice coefficient of 0.828 for vessel segmentation. On the public XCAD dataset, our model sets a new state-of-the-art benchmark with a Dice coefficient of 0.755, surpassing both unsupervised and supervised learning approaches. This method achieves robust single-frame subtraction and demonstrates that combining pretraining with minimal fine-tuning enables accurate coronary vessel segmentation with limited manual annotations. We successfully apply this approach to assist physicians in visualizing potential vascular stenosis sites during coronary angiography. Code, dataset, and a live demo will be available available at: . [ABSTRACT FROM AUTHOR]

The primary aim of this investigation was to leverage radiomics features derived from contrast-enhanced abdominal computed tomography (CT) scans to devise a predictive model to discern the benign and malignant nature of intraductal papillary mucinous neoplasms (IPMNs). Radiomic signatures were meticulously crafted to delineate benign from malignant IPMNs by extracting pertinent features from contrast-enhanced CT images within a designated training cohort (n = 84). Subsequent validation was conducted with data from an independent test cohort (n = 37). The discriminative ability of the model was quantitatively evaluated through receiver operating characteristic (ROC) curve analysis, with the integration of carefully selected clinical features to improve the comparative analysis. Arterial-phase images were utilized to construct a model comprising 8 features for distinguishing between benign and malignant cases. The model achieved an accuracy of 0.891 [95% confidence interval (95% CI), 0.816–0.996] in the cross-validation set and 0.553 (95% CI 0.360–0.745) in the test set. Conversely, employing 9 features from the venous-phase resulted in a model with a cross-validation accuracy of 0.862 (95%CI 0.777–0.946) and a test set accuracy of 0.801 (95% CI 0.653–0.950).Integrating the identified clinical features with imaging features yielded a model with a cross-validation accuracy of 0.934 (95% CI 0.879–0.990) and a test set accuracy of 0.904 (95% CI 0.808–0.999), thereby further improving its discriminatory ability. Our findings distinctly illustrate that venous-phase radiomics features eclipse arterial-phase radiomic features in terms of predictive accuracy regarding the nature of IPMNs. Furthermore, the synthesis and meticulous screening of clinical features with radiomic data significantly increased the diagnostic efficacy of our model, underscoring the pivotal importance of a comprehensive and integrated approach for accurate risk stratification in IPMN management. [ABSTRACT FROM AUTHOR]

The stability of ecosystems in high mountain canyon areas is poor, and the interaction between humans and the land is complex, making these ecosystems more vulnerable to destruction. Quantitatively assessing the ecosystem service value (ESV) in high mountain canyon areas and revealing its spatiotemporal evolution patterns and driving factors play a crucial role in the construction of regional ecological barriers and the assurance of ecological security. This study focuses on the Upper Minjiang River as the research area, using the InVEST model and the Equivalent Factor Method to estimate ESV. This combination aims to address the inadequacy of the Equivalent Factor Method in reflecting the variability of ESV across different regions, and the sensitivity of the InVEST model to data changes that results in insufficient accuracy of ESV assessments. By harnessing spatial au-tocorrelation and the geodetector method, we unravel the spatiotemporal evolution characteristics and driving factors of ESV. The results show that: (1) From 2000 to 2020, the ESVs estimated by the two estimations increased by 31.28% and 22.47%, respectively, both indicating that the eco-environment quality of the upper Minjiang River has been continuously improved. (2) When Moran's I was greater than 0.5 (p < 0.05), the spatial clustering of "High-High" and "Low-Low" ESV was obvious. It is clear that the ESV varies geographically. High values are primarily found in the study area's center and southern regions, as well as on both banks of the Minjiang River, whereas low values are more common in the region's northern region. (3) Slope and human activity intensity (HAI) are the principal contributors to the spatial differentiation of the ESV, more than 60% of the interaction types between the two factors were classified as dual-factor enhancement. The synergistic reinforcing effects of HAI, slope, elevation, and temperature collectively shape the shifts in ESV spatial distribution. This study offers a novel evaluative lens on the ESV of the Upper Minjiang River area, supplying a sturdy data support for crafting specific ecological preservation and rejuvenation strategies in the coming years., (© 2024. The Author(s).)

Reticulocalbin 1 (RCN1), a calcium-binding protein located in the endoplasmic reticulum (ER) lumen, contains six conserved regions. Its main functions include maintaining intracellular homeostasis and regulating cell proliferation and apoptosis, and it plays an important role in the development of various tumours. However, the exact function of RCN1 in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the aim of this study was to investigate the effects of RCN1 on the biological behaviour of OSCC and the regulation of tumour-associated macrophage (TAM) polarization. The expression of RCN1 in OSCC and normal oral mucosa was evaluated through bioinformatics analysis and immunohistochemical staining. The growth, migration, and invasion of OSCC cells were observed after knockdown of RCN1 using CCK-8 and Transwell assays. Apoptosis was detected by flow cytometry. The effect of tumour cell-derived RCN1 on the polarization of THP-1 macrophages was investigated by establishing a coculture model of THP-1 macrophages and OSCC cells. Additionally, changes in the expression levels of relevant proteins were detected using Western blotting. The upregulation of RCN1 in tumour tissues compared to normal oral mucosal tissues is associated with a poor prognosis and can be utilized as a prognostic indicator for OSCC. Knockdown of RCN1 inhibited the proliferation, migration, and invasion of OSCC cells. Additionally, knockdown of RCN1 in Cal-27 and SCC-25 cells resulted in inhibition of the M2 polarization of THP-1 macrophages. RCN1 knockdown inhibits OSCC progression and M2 macrophage polarization. Targeting RCN1 may be a promising approach for OSCC treatment. [ABSTRACT FROM AUTHOR]

This research aims to fabricate an AlSi10Mg parts using Laser Powder Bed Fusion technique with enhanced structural integrity. The prime novelty of this research work is eliminating the balling and sparring effects, keyhole and cavity formation by attaining effective melt pool formation. Modelling of the Laser Powder Bed Fusion process parameters such as Laser power, scanning speed, layer thickness and hatch spacing is carried out through Complex Proportional Assessment technique to optimize the parts' surface attributes and to overcome the defects based on the output responses such as surface roughness on scanning and building side, hardness and porosity. The laser power of 350 W, layer thickness of 30 µm, scan speed of 1133 mm/s, and hatch spacing of 0.1 mm produces significantly desirable results to achieve maximum hardness and minimum surface roughness and holding the porosity of < 1%. The obtained optimal setting from this research improves the structural integrity of the printed AlSi10Mg parts. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the performance of traditional-deep learning combination model based on Doppler ultrasound for diagnosing malignant complex cystic and solid breast nodules. A conventional statistical prediction model based on the ultrasound features and basic clinical information was established. A deep learning prediction model was used to train the training group images and derive the deep learning prediction model. The two models were validated, and their accuracy rates were compared using the data and images of the test group, respectively. A logistic regression method was used to combine the two models to derive a combination diagnostic model and validate it in the test group. The diagnostic performance of each model was represented by the receiver operating characteristic curve and the area under the curve. In the test cohort, the diagnostic efficacy of the deep learning model was better than traditional statistical model, and the combined diagnostic model was better and outperformed the other two models (combination model vs traditional statistical model: AUC: 0.95 > 0.70, P = 0.001; combination model vs deep learning model: AUC: 0.95 > 0.87, P = 0.04). A combination model based on deep learning and ultrasound features has good diagnostic value. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges' g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges' g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges' g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges' g = − 0.795; 95% CI = − 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges' g = 0.182; 95% CI = − 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD. [ABSTRACT FROM AUTHOR]

The prognostic factors for survival among patients with secondary osteosarcoma remain unclear. The aim of this study was to develop a practical nomogram for predicting cancer-specific survival (CSS) in patients with osteosarcoma as a secondary malignancy. The surveillance, epidemiology, and end results database was used for the identification of osteosarcoma cases. The total sample comprised 5860 cases of primary osteosarcoma and 268 cases of secondary osteosarcoma during the period from 1973 to 2015. The CSS and overall survival (OS) of primary and secondary osteosarcomas were analyzed. The predictors of CSS for secondary osteosarcoma were identified and integrated to build a nomogram. Validation of the nomogram was performed using concordance index (C-index) and calibration plots. The results indicated that patients with secondary osteosarcoma had poorer CSS and OS than patients with primary osteosarcoma. The nomogram model exhibited high discriminative accuracy in the training cohort (C-index = 0.826), which was confirmed in the internal validation cohort (C-index = 0.791). In addition, the calibration plots confirmed good concordance for prediction of CSS at 3, 5, and 10 years. In conclusion, we developed a practical nomogram that provided individual predictions of CSS for patients with secondary osteosarcoma. This nomogram may help clinicians with prognostic evaluations and with the development of individualized therapies for this aggressive disease. [ABSTRACT FROM AUTHOR]

Low L3 skeletal muscle area (SMA), which is assessed on computed tomography (CT) images, has been reported to indicate poor clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). The dorsal muscle group area at the T12 vertebral level (T12DMA) was used as an alternative to L3 SMA. This study aimed to investigate whether T12DMA could be used as a predictor of in-hospital mortality and long-term survival in elderly patients with COPD admitted to the intensive care unit (ICU). This single-center retrospective case–control study was performed by analyzing the clinical information and measuring T12DMA on chest CT images of elderly patients with COPD admitted to the ICU between May 2013 and May 2018. This study included 136 patients. The multivariate logistic regression analysis showed that T12DMA, neutrophil–lymphocyte ratio, invasive mechanical ventilation, and systemic steroid therapy were independent risk factors for predicting the hospital mortality. The median survival was significantly higher in the high-T12DMA group (214 days) than in the low-T12DMA group (32 days). [ABSTRACT FROM AUTHOR]

Invasive candidiasis is one of the most common nosocomial fungal infections worldwide. Delayed implementation of effective antifungal treatment caused by inefficient Candida diagnosis contributes to its notoriously high mortality rates. The availability of better Candida diagnostic tools would positively impact patient outcomes. Here, we report on the development of a single-tube, dual channel pentaplex molecular diagnostic assay based on Multiplex Probe Amplification (MPA) technology. It allows simultaneous identification of C. auris, C. glabrata and C. krusei, at species-level as well as of six additional albicans and non-albicans pathogenic Candida at genus level. The assay overcomes the one-channel one-biomarker limitation of qPCR-based assays. Assay specificities are conferred by unique biomarker probe pairs with characteristic melting temperatures; post-amplification melting curve analysis allows simple identification of the infectious agent. Alerting for the presence of C. auris, the well-characterised multi-drug resistant outbreak strain, will facilitate informed therapy decisions and aid antifungal stewardship. The MPA-Candida assay can also be coupled to a pan-Fungal assay when differentiation between fungal and bacterial infections might be desirable. Its multiplexing capacity, detection range, specificity and sensitivity suggest the potential use of this novel MPA-Candida assay in clinical diagnosis and in the control and management of hospital outbreaks. [ABSTRACT FROM AUTHOR]

Microbial metabolisms of arsenic, iron, sulfur, nitrogen and organic matter play important roles in arsenic mobilization in aquifer. In this study, microbial community composition and functional potentials in a high arsenic groundwater were investigated using integrated techniques of RNA- and DNA-based 16S rRNA gene sequencing, metagenomic sequencing and functional gene arrays. 16S rRNA gene sequencing showed the sample was dominated by members of Proteobacteria (62.3–75.2%), such as genera of Simplicispira (5.7–6.7%), Pseudomonas (3.3–5.7%), Ferribacterium (1.6–4.4%), Solimonas (1.8–3.2%), Geobacter (0.8–2.2%) and Sediminibacterium (0.6–2.4%). Functional potential analyses indicated that organics degradation, assimilatory sulfate reduction, As-resistant pathway, iron reduction, ammonification, nitrogen fixation, denitrification and dissimilatory nitrate reduction to ammonia were prevalent. The composition and function of microbial community and reconstructed genome bins suggest that high level of arsenite in the groundwater may be attributed to arsenate release from iron oxides reductive dissolution by the iron-reducing bacteria, and subsequent arsenate reduction by ammonia-producing bacteria featuring ars operon. This study highlights the relationship between biogeochemical cycling of arsenic and nitrogen in groundwater, which potentially occur in other aquifers with high levels of ammonia and arsenic. [ABSTRACT FROM AUTHOR]

It has been reported that geographical variation influences bone mineral density (BMD), obesity, and sarcopenia related traits in other countries. However, there is lack of similar studies in the US population. In this study, we compared data from three US study cohorts to evaluate geographical variations of BMD and body composition. BMD, fat mass and lean mass were collected from Dual-energy X-ray absorptiometry machine. ANCOVA and Chi-square tests were used to compare the differences between BMDs, obesity and sarcopenia related traits from different regional sites (Omaha, Kansas City and Baton Rouge/New Orleans). Eta-squared was used to measure the effect sizes of these differences. A total of 11,315 Caucasians from our previous three study cohorts were compared. There was no significant geographical difference in BMD for males or females under the criteria of p-values < 0.05 and effect size η2 > 0.01. There were significant geographical differences with medium effect size (p-value < 0.001, 0.01 < η2 < 0.14) for whole body fat mass percentage and index of low muscle mass. For Caucasians in the United States, there is no significant geographical effect found on BMD. The obesity and sarcopenia related traits are significantly different between the three study cohorts. [ABSTRACT FROM AUTHOR]

In this work, we have successfully demonstrated the junctionless (JL) transistors with two-dimensional-like (2D-like) nano-sheet (NS) material, amorphous indium tungsten oxide (a-IWO), as an active channel layer. The influences of the different gate insulator (GI) materials and the scalings of GI thickness, a-IWO channel thickness, and channel lengths on the a-IWO NS JL transistors (a-IWO NS-JLTs) have been studied for the purposes of low operation voltage (gate voltage ≤2V) and high performance. The 2D-like a-IWO NS-JLTs exhibit low operation voltage, low source/drain (S/D) contact resistance (RC) and other key electrical characteristics, such as high field-effect mobility (μFE), near ideal subthreshold swing (S.S.), and large ON/OFF currents ratio (ION/IOFF). The remarkable device characteristics also make the proposed 2D-like a-IWO NS-JLTs promising for system-on-panel (SoP) and vertically stacked (VS) hybrid CMOS applications. [ABSTRACT FROM AUTHOR]

Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARβ/δ on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPARβ/δ-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that Ad-PPARβ/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARβ/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. [ABSTRACT FROM AUTHOR]