Two-Dimensional Peptide Assembly via Arene-Perfluoroarene Interactions for Proliferation and Differentiation of Myoblasts.

Supramolecular assembly based on aromatic interactions can provide well-defined nanostructures with an understanding of intermolecular interactions at the molecular level. The peptide assembly via a supramolecular approach can overcome the inherent limitations of bioactive peptides, such as proteolytic degradations and rapid internalizations into the cytosol. Although extensive research has been carried out on supramolecular peptide materials with a two-dimensional (2D) structure, more needs to be reported on biological activity studies using well-defined 2D peptide materials. Physical and chemical properties of the 2D peptide assembly attributed to their large surface area and flexibility can show low cytotoxicity, enhanced molecular loading, and higher bioconjugation efficiency in biological applications. Here, we report supramolecular 2D materials based on the pyrene-grafted amphiphilic peptide, which contains a peptide sequence (Asp-Gly-Glu-Ala; DGEA) that is reported to bind to the integrin α2ß1 receptor in 2D cell membranes. The addition of octafluoronaphthalene (OFN) to the pyrene-grafted peptide could induce a well-ordered 2D assembly by face-centered arene-perfluoroarene stacking. The DGEA-peptide 2D assembly with a flat structure, structural stability against enzymatic degradations, and a larger size can enhance the proliferation and differentiation of muscle cells via continuous interactions with cell membrane receptors integrin α2ß1 showing a low intracellular uptake (15%) compared to that (62%) of the vesicular peptide assembly. These supramolecular approaches via the arene-perfluoroarene interaction provide a strategy to fabricate well-defined 2D peptide materials with an understanding of assembly at the molecular level for the next-generation peptide materials.

Detection of Multiple Respiration Patterns Based on 1D SNN from Continuous Human Breathing Signals and the Range Classification Method for Each Respiration Pattern.

Human respiratory information is being used as an important source of biometric information that can enable the analysis of health status in the healthcare domain. The analysis of the frequency or duration of a specific respiration pattern and the classification of respiration patterns in the corresponding section for a certain period of time are important for the utilization of respiratory information in various ways. Existing methods require window slide processing to classify sections for each respiration pattern from the breathing data for a certain time period. In this case, when multiple respiration patterns exist within one window, the recognition rate can be lowered. To solve this problem, a 1D Siamese neural network (SNN)-based human respiration pattern detection model and a merge-and-split algorithm for the classification of multiple respiration patterns in each region for all respiration sections are proposed in this study. When calculating the accuracy based on intersection over union (IOU) for the respiration range classification result for each pattern, the accuracy was found to be improved by approximately 19.3% compared with the existing deep neural network (DNN) and 12.4% compared with a 1D convolutional neural network (CNN). The accuracy of detection based on the simple respiration pattern was approximately 14.5% higher than that of the DNN and 5.3% higher than that of the 1D CNN.

Effect of No-ozone Cold Plasma on Regeneration after Crushed Mental Nerve Injury in rats.

Background: This experimental research aimed to determine whether No-ozone Cold Plasma (NCP) has regenerative effect on crushed injured sensory nerves in a rat model (Wistar A) and to evaluate whether NCP can be used as an alternative treatment method for sensory nerve injury in the oral-maxillofacial region. Methods: A total of 10 Wistar A rats were used for this experiment. They were divided into three groups according to whether the mental nerve of the left mandible was injured and NCP was applied or not: group 1 (n=3) (non-mental nerve damage, non-MD) - the left mental nerve was exposed and non-damaged; group 2 (n=3) (mental nerve damage, MD) - the left mental nerve was exposed and damaged, NCP was not applied; and group 3 (n=4) (mental nerve damage and NCP, MD-NCP) - the left mental nerve was exposed and damaged, NCP was applied with regular intervals (three times a week). Results: For the behavior analysis, von Frey test was used. Furthermore, the nerve tissues were examined with hematoxylin and eosin (H&E) staining, and the extent of neurorecovery was evaluated with the immunofluorescence staining of certain markers. The behavioral analysis showed that the function recovery sensory nerve was faster in group 3 (MD-NCP). In the histomorphologic and immunofluorescence analyses, the expression of the factors involved in neurorecovery was much higher in group 3 than in group 2 (MD). Conclusions: The expeditious recovery of sensory nerve function as well as the higher expression of the factors indicating nerve function recovery in the NCP-treated group suggest that NCP has a positive effect on regeneration after sensory nerve crushing injury. Therefore, in the case of sensory impairment of the oral-maxillofacial region, no-ozone cold plasma can be applied for therapeutic effect.

ErbB3-Targeting Oncolytic Adenovirus Causes Potent Tumor Suppression by Induction of Apoptosis in Cancer Cells.

Cancer is a multifactorial and deadly disease. Despite major advancements in cancer therapy in the last two decades, cancer incidence is on the rise and disease prognosis still remains poor. Furthermore, molecular mechanisms of cancer invasiveness, metastasis, and drug resistance remain largely elusive. Targeted cancer therapy involving the silencing of specific cancer-enriched proteins by small interfering RNA (siRNA) offers a powerful tool. However, its application in clinic is limited by the short half-life of siRNA and warrants the development of efficient and stable siRNA delivery systems. Oncolytic adenovirus-mediated therapy offers an attractive alternative to the chemical drugs that often suffer from innate and acquired drug resistance. In continuation to our reports on the development of oncolytic adenovirus-mediated delivery of shRNA, we report here the replication-incompetent (dAd/shErbB3) and replication-competent (oAd/shErbB3) oncolytic adenovirus systems that caused efficient and persistent targeting of ErbB3. We demonstrate that the E1A coded by oAd/shErbB, in contrast to dAd/shErbB, caused downregulation of ErbB2 and ErbB3, yielding stronger downregulation of the ErbB3-oncogenic signaling axis in in vitro models of lung and breast cancer. These results were validated by in vivo antitumor efficacy of dAd/shErbB3 and oAd/shErbB3.

White matter hyperintensities segmentation using the ensemble U-Net with multi-scale highlighting foregrounds.

White matter hyperintensities (WMHs) are abnormal signals within the white matter region on the human brain MRI and have been associated with aging processes, cognitive decline, and dementia. In the current study, we proposed a U-Net with multi-scale highlighting foregrounds (HF) for WMHs segmentation. Our method, U-Net with HF, is designed to improve the detection of the WMH voxels with partial volume effects. We evaluated the segmentation performance of the proposed approach using the Challenge training dataset. Then we assessed the clinical utility of the WMH volumes that were automatically computed using our method and the Alzheimer's Disease Neuroimaging Initiative database. We demonstrated that the U-Net with HF significantly improved the detection of the WMH voxels at the boundary of the WMHs or in small WMH clusters quantitatively and qualitatively. Up to date, the proposed method has achieved the best overall evaluation scores, the highest dice similarity index, and the best F1-score among 39 methods submitted on the WMH Segmentation Challenge that was initially hosted by MICCAI 2017 and is continuously accepting new challengers. The evaluation of the clinical utility showed that the WMH volume that was automatically computed using U-Net with HF was significantly associated with cognitive performance and improves the classification between cognitive normal and Alzheimer's disease subjects and between patients with mild cognitive impairment and those with Alzheimer's disease. The implementation of our proposed method is publicly available using Dockerhub (https://hub.docker.com/r/wmhchallenge/pgs).

CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression.

CRISPR-Cas12a represents a class 2/type V CRISPR RNA-guided endonuclease, holding promise as a precise genome-editing tool in vitro and in vivo. For efficient delivery of the CRISPR-Cas system into cancer, oncolytic adenovirus (oAd) has been recognized as a promising alternative vehicle to conventional cancer therapy, owing to its cancer specificity; however, to our knowledge, it has not been used for genome editing. In this study, we show that CRISPR-Cas12a mediated by oAd disrupts the oncogenic signaling pathway with excellent cancer specificity. The intratumoral delivery of a single oAd co-expressing a Cas12a and a CRISPR RNA (crRNA) targeting the epidermal growth factor receptor (EGFR) gene (oAd/Cas12a/crEGFR) induces efficient and precise editing of the targeted EGFR gene in a cancer-specific manner, without detectable off-target nuclease activity. Importantly, oAd/Cas12a/crEGFR elicits a potent antitumor effect via robust induction of apoptosis and inhibition of tumor cell proliferation, ultimately leading to complete tumor regression in a subset of treated mice. Collectively, in this study we show precise genomic reprogramming via a single oAd vector-mediated CRISPR-Cas system and the feasibility of such system as an alternative cancer therapy.

Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials.

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in 'cold' or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn 'cold' tumors 'hot,' increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.

Ethanol extract of asiasari radix preferentially induces apoptosis in G361 human melanoma cells by differential regulation of p53.

BACKGROUND: In Korea and China, asiasari radix (AR) is widely used as a traditional anti-inflammatory and analgesic agent. After its skin-regenerating and hair loss-preventing activities were identified, several types of AR extracts were used for aesthetic purposes. Nevertheless, the effect of ARE on various types of skin cancers was not fully studied yet. METHODS: In this study, we tested the effect of an ethanolic AR extract (ARE) on G361 human melanoma and HaCaT human keratinocyte cell lines. After ARE exposure, cell growth and the expression patterns of proteins and genes were monitored. RESULTS: The ARE-mediated cell growth inhibition was greater in G361 cells than in HaCaT cells due to differences in its cell growth regulation effects. Interestingly, ARE treatment induced caspase-3-mediated apoptosis in G361 cells, but not in HaCaT cells. Furthermore, ARE reduced the expression of p53 and p21 proteins in G361 cells, whereas it induced their expression in HaCaT cells. ARE induced cell death in G361 cells through the reactive oxygen species (ROS)-dependent regulation of p53 and p21 in G361 cells. Microarray analysis showed that ARE regulates Mouse double minute 2 homolog (MDM2) and CASP8 and FADD-like apoptosis regulator (CFLAR) gene expression in G361 and HaCaT cells differently. CONCLUSION: The treatment of ARE preferentially induces apoptosis in melanoma cells by the ROS-dependent differential regulation of p53 level. Therefore, ARE can be used as a new medicinal option for melanoma.

Potent antitumor effect of tumor microenvironment-targeted oncolytic adenovirus against desmoplastic pancreatic cancer.

Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression. A decorin-expressing oncolytic adenovirus (Ad; oH(E)mT-DCN) replicating under the control of the H(E)mT promoter induced more potent and highly cancer-specific cell death compared with its cognate control oncolytic Ad, which harbored the endogenous Ad E1A promoter. Moreover, oH(E)mT-DCN exhibited enhanced antitumor efficacy compared with both the clinically approved oncolytic Ad ONYX-015 and its cognate control oncolytic Ad lacking DCN. oH(E)mT-DCN treatment also attenuated the expression of major ECM components, such as collagen I/III, elastin and fibronectin and induced tumor cell apoptosis, leading to extensive viral dispersion within orthotopic pancreatic tumors and pancreatic cancer patient-derived tumor spheroids. Collectively, these findings demonstrate that oH(E)mT-DCN exhibits potent antitumor efficacy by degrading the ECM and inducing apoptosis in a multifunctional process. This process facilitates the dispersion and replication of oncolytic Ad, making it an attractive candidate for the treatment of aggressive and desmoplastic pancreatic cancer.

Amyloid Deposits and Idiopathic Normal-Pressure Hydrocephalus: An 18F-Florbetaben Study.

BACKGROUND: The first aim of our study was to determine whether cortical 18F-florbetaben retention was different between healthy controls and idiopathic normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate whether there were any relationships between 18F-florbetaben retention and either hippocampal volume or clinical symptoms in INPH patients. METHODS: Seventeen patients diagnosed with INPH and 8 healthy controls underwent studies with magnetic resonance imaging and 18F-florbetaben positron emission tomography imaging. RESULTS: Automated region-of-interest analysis showed significant increases in 18F-florbetaben uptake in several brain regions in INPH patients compared to control subjects, with especially remarkable increases in the frontal (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the INPH group, right hippocampal volume was found to be negatively correlated with right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination scores negatively correlated with right occipital 18F-florbetaben retention. Higher 18F-florbetaben retention correlated significantly with a higher Clinical Dementia Rating Scale score in the right occipital cortex. CONCLUSIONS: Our results indicate that INPH might be a disease exhibiting a characteristic pattern of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal cortex may be related to hippocampal neuronal degeneration. Our findings may also help us understand the potential pathophysiology of cognitive impairments associated with INPH.

Retrosplenial cortical thinning as a possible major contributor for cognitive impairment in HIV patients.

OBJECTIVES: To identify brain cortical regions relevant to HIV-associated neurocognitive disorder (HAND) in HIV patients. METHODS: HIV patients with HAND (n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched, seronegative controls (n = 11) were recruited. All participants were male and underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of interest (ROI) analyses were performed to analyse cortical thickness. RESULTS: Compared to controls, both HIV-IC and HAND showed decreased cortical thickness mainly in the bilateral primary sensorimotor areas, extending to the prefrontal and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal cortex, left inferior parietal lobule, bilateral superior medial prefrontal cortices, right temporoparietal junction and left hippocampus, and cortical thickening in the left middle occipital cortex. Left retrosplenial cortical thinning showed significant correlation with slower information processing, declined verbal memory and executive function, and impaired fine motor skills. CONCLUSIONS: This study supports previous research suggesting the selective vulnerability of the primary sensorimotor cortices and associations between cortical thinning in the prefrontal and parietal cortices and cognitive impairment in HIV-infected patients. Furthermore, for the first time, we propose retrosplenial cortical thinning as a possible major contributor to HIV-associated cognitive impairment. KEY POINTS: • Primary sensorimotor and supplementary motor cortices were selectively vulnerable to HIV infection • Prefrontal and parietal cortical thinning was associated with HIV-associated cognitive impairment • Retrosplenial cortical thinning might be a major contributor to HIV-associated cognitive impairment.

The topical application of low-temperature argon plasma enhances the anti-inflammatory effect of Jaun-ointment on DNCB-induced NC/Nga mice.

BACKGROUND: Jaun-ointment (JO), also known as Shiunko in Japan, is one of the most popular medicinal formulae used in Korean traditional medicine for the external treatment of skin wound and inflammatory skin conditions. Since JO is composed of crude mixture of two herbal extracts (radix of Lithospermum erythrorhizon Siebold & Zucc and Angelica gigas Nakai), those been proved its anti-inflammatory activities in-vitro and in-vivo, JO has been expected as a good alternative treatment option for atopic dermatitis (AD). However, due to the lack of strategies for the penetrating methods of JO's various anti-inflammatory elements into the skin, an effective and safe transdermal drug delivery system needs to be determined. Here, low-temperature argon plasma (LTAP) was adopted as an ancillary partner of topically applied JO in a mice model of AD and the effectiveness was examined. METHODS: Dorsal skins of NC/Nga mice were challenged with DNCB (2,4-dinitrochlorobenzene) to induce AD. AD-like skin lesions were treated with JO alone, or in combination with LTAP. Inflammatory activity in the skin tissues was evaluated by histological analysis and several molecular biological tests. RESULTS: LTAP enhanced the effect of JO on AD-like skin lesion. Topical application of JO partially inhibited the development of DNCB-induced AD, shown by the moderate reduction of eosinophil homing and pro-inflammatory cytokine level. Combined treatment of JO and LTAP dramatically inhibited AD phenotypes. Interestingly, treatment with JO alone did not affect the activity of nuclear factor (NF)κB/RelA in the skin, but combined treatment of LTAP-JO blocked DCNB-mediated NFκB/RelA activation. CONCLUSIONS: LTAP markedly enhanced the anti-inflammatory activity of JO on AD-like skin lesions. The effect of LTAP may be attributed to enhancement of drug penetration and regulation of NFκB activity. Therefore, the combination treatment of JO and LTAP could be a potential strategy for the treatment of AD.

Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3ß inhibitor enhances antitumor immune response against bladder cancer.

Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3ß inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.

Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy.

Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and (2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive regulatory T cells than any other treatment groups. Collectively, oAd/APP+DC led to superior induction of antitumor immune response and amelioration of immunosuppressive tumor microenvironment to elicit potent tumor growth inhibition than either monotherapy.

No-ozone cold plasma induces apoptosis in human neuroblastoma cell line via increased intracellular reactive oxygen species (ROS).

BACKGROUND: This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis. METHODS: Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected. RESULTS: NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells. CONCLUSION: These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.

Superoxide Dismutase-Mimetic Polyphenol-Based Carbon Dots for Multimodal Bioimaging and Treatment of Atopic Dermatitis.

Polyphenols have been investigated for their potential to mitigate inflammation in the context of atopic dermatitis (AD). In this study, epigallocatechin-3-gallate (EGCG)-based carbon dots (EGCG@CDs) were developed to enhance transdermal penetration, reduce inflammation, recapitulate superoxide dismutase (SOD) activity, and provide antimicrobial effects for AD treatment. The water-soluble EGCG@CDs in a few nanometers size exhibit a negative zeta potential, making them suitable for effective transdermal penetration. The fluorescence properties, including an upconversion effect, make EGCG@CDs suitable imaging probes for both in vitro and in vivo applications. By mimicking the SOD enzyme, EGCG@CDs scavenge reactive oxygen species (ROS) and actively produce hydrogen peroxide through a highly catalytic capability toward the oxygen reduction reaction, resulting in the inhibition of bacterial growth. The enhanced antioxidant properties, high charge mobility, and various functional groups of EGCG@CDs prove effective in reducing intracellular ROS in an in vitro AD model. In the mouse AD model, EGCG@CDs incorporated into a hydrogel actively penetrated the epidermal layer, leading to ROS scavenging, reduced mast cell activation, and histological recovery of skin barriers. This research represents the versatile potential of EGCG@CDs in addressing AD and advancing tissue engineering.

General psychopathology factor (p-factor) prediction using resting-state functional connectivity and a scanner-generalization neural network.

The general psychopathology factor (p-factor) represents shared variance across mental disorders based on psychopathologic symptoms. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to investigate functional networks (FNs) from functional magnetic resonance imaging (fMRI) associated with the psychopathology of an adolescent cohort (n > 10,000). However, the heterogeneities associated with the use of multiple sites and multiple scanners in the ABCD Study need to be overcome to improve the prediction of the p-factor using fMRI. We proposed a scanner-generalization neural network (SGNN) to predict the individual p-factor by systematically reducing the scanner effect for resting-state functional connectivity (RSFC). We included 6905 adolescents from 18 sites whose fMRI data were collected using either Siemens or GE scanners. The p-factor was estimated based on the Child Behavior Checklist (CBCL) scores available in the ABCD study using exploratory factor analysis. We evaluated the Pearson's correlation coefficients (CCs) for p-factor prediction via leave-one/two-site-out cross-validation (LOSOCV/LTSOCV) and identified important FNs from the weight features (WFs) of the SGNN. The CCs were higher for the SGNN than for alternative models when using both LOSOCV (0.1631 ± 0.0673 for the SGNN vs. 0.1497 ± 0.0710 for kernel ridge regression [KRR]; p < 0.05 from a two-tailed paired t-test) and LTSOCV (0.1469 ± 0.0381 for the SGNN vs. 0.1394 ± 0.0359 for KRR; p = 0.01). It was found that (a) the default-mode and dorsal attention FNs were important for p-factor prediction, and (b) the intra-visual FN was important for scanner generalization. We demonstrated the efficacy of our novel SGNN model for p-factor prediction while simultaneously eliminating scanner-related confounding effects for RSFC.

Peptide Assembly of Different Dimensions and Their Effect on Myoblast Proliferation.

Variations in the functionalities of materials of different dimensions containing the same functional groups can be attributed to the structural stability and morphology of the materials. The morphology of peptide assemblies can influence their interactions with biological systems and ultimately modulate their bioactivity. Among reported Arg-Gly-Asp (RGD)-based supramolecular materials, two-dimensional (2-D) peptide assembly has been rarely studied. Herein, we report the fabrication of RGD-based supramolecular one-dimensional (1-D) and 2-D assemblies as peptide-based myoblast growth accelerators. The 2-D assembly was more effective in proliferating C2C12 cells than the 1-D assembly. These findings provide insights into the construction of optimal RGD-based supramolecular functional materials of different dimensions.

Oncolytic adenovirus as pancreatic cancer-targeted therapy: Where do we go from here?

Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic cancer is refractory to conventional cancer treatment options, like chemotherapy and radiotherapy, and commercialized immunotherapeutics, owing to its immunosuppressive and desmoplastic phenotype. Due to these reasons, development of an innovative treatment option that can overcome these challenges posed by the pancreatic tumor microenvironment (TME) is in an urgent need. The present review aims to summarize the evolution of oncolytic adenovirus (oAd) engineering and usage as therapeutics (either monotherapy or combination therapy) over the last decade to overcome these hurdles to instigate a potent antitumor effect against desmoplastic and immunosuppressive pancreatic cancer.

Fully Automated Segmentation of Human Eyeball Using Three-Dimensional U-Net in T2 Magnetic Resonance Imaging.

Purpose: To develop and validate a fully automated deep-learning-based tool for segmentation of the human eyeball using a three-dimensional (3D) U-Net, compare its performance to semiautomatic segmentation ground truth and a two-dimensional (2D) U-Net, and analyze age and sex differences in eyeball volume, as well as gaze-dependent volume consistency in normal subjects. Methods: We retrospectively collected 474 magnetic resonance imaging (MRI) scans, including different gazing scans, from 119 patients. A 10-fold cross-validation was applied to separate the dataset into training, test, and validation sets for both the 3D U-Net and 2D U-Net. Performance accuracy was measured using four quantitative metrics compared to the ground truth, and Bland-Altman plot analysis was conducted. Age and sex differences in eyeball volume and variability in eyeball volume differences across gazing directions were analyzed. Results: The 3D U-Net outperformed the 2D U-Net with mean accuracy scores >0.95, showing acceptable agreement in the Bland-Altman plot analysis despite a tendency for slight overestimation (mean difference = -0.172 cm³). Significant sex differences and age effects on eyeball volume were observed for both methods (P < 0.05). No significant volume differences were found between the segmentation methods or within each method for the different gazing directions. Significant differences in performance accuracy were identified among the five gazing directions, with the upward direction showing a notably lower performance. Conclusions: Our study demonstrated the effectiveness of 3D U-Net human eyeball volume segmentation using T2-weighted MRI. The robustness and reliability of 3D U-Net across diverse populations and gaze directions support enhanced ophthalmic diagnosis and treatment strategies. Translational Relevance: Our findings demonstrate the feasibility of using the proposed 3D U-Net model for the automatic segmentation of the human eyeball, with potential applications in various ophthalmic research fields that require the analysis of 3D geometric eye globe shapes or eye movement detection.