Over the past decade, conductive hydrogels have received great attention as tissue-interfacing electrodes due to their soft and tissue-like mechanical properties. However, a trade-off between robust ...tissue-like mechanical properties and good electrical properties has prevented the fabrication of a tough, highly conductive hydrogel and limited its use in bioelectronics. Here, we report a synthetic method for the realization of highly conductive and mechanically tough hydrogels with tissue-like modulus. We employed a template-directed assembly method, enabling the arrangement of a disorder-free, highly-conductive nanofibrous conductive network inside a highly stretchable, hydrated network. The resultant hydrogel exhibits ideal electrical and mechanical properties as a tissue-interfacing material. Furthermore, it can provide tough adhesion (800 J/m
) with diverse dynamic wet tissue after chemical activation. This hydrogel enables suture-free and adhesive-free, high-performance hydrogel bioelectronics. We successfully demonstrated ultra-low voltage neuromodulation and high-quality epicardial electrocardiogram (ECG) signal recording based on in vivo animal models. This template-directed assembly method provides a platform for hydrogel interfaces for various bioelectronic applications.
An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent ...large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity.
Abstract
A knowledgebase of the systematic functional annotation of fusion genes is critical for understanding genomic breakage context and developing therapeutic strategies. FusionGDB is a unique ...functional annotation database of human fusion genes and has been widely used for studies with diverse aims. In this study, we report fusion gene annotation updates aided by deep learning (FusionGDB 2.0) available at https://compbio.uth.edu/FusionGDB2/. FusionGDB 2.0 has substantial updates of contents such as up-to-date human fusion genes, fusion gene breakage tendency score with FusionAI deep learning model based on 20 kb DNA sequence around BP, investigation of overlapping between fusion breakpoints with 44 human genomic features across five cellular role's categories, transcribed chimeric sequence and following open reading frame analysis with coding potential based on deep learning approach with Ribo-seq read features, and rigorous investigation of the protein feature retention of individual fusion partner genes in the protein level. Among ∼102k fusion genes, about 15k kept their ORF as In-frames, which is two times compared to the previous version, FusionGDB. FusionGDB 2.0 will be used as the reference knowledgebase of fusion gene annotations. FusionGDB 2.0 provides eight categories of annotations and it will be helpful for diverse human genomic studies.
Abstract
Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for ...OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.
Graphics Processing Units (GPUs) have been employed in embedded systems to handle increased amounts of computation and to satisfy the timing requirement. Due to the small feature size, chip aging and ...within-die parameter variations have been considered to be among the challenging problems for state-of-the-art processors, including GPUs. In order to deal with the process variation, several processors use chip-level guardbanding, which uses the lowest operating frequency that results in a significant chip-level performance drop. Other processors improve their performance efficiency through core-level guardbanding that may use a different operating frequency for each core. Existing aging management techniques are based on the chip-level guardbanding, which assigns the same number of instructions to the cores that have the same aging status. However, in the presence of the process variation, existing aging management techniques have a limitation in minimizing the aging effect because each core has a different amount of stress for the same number of instructions. In order to tackle this problem, we propose a low-overhead aging and process variation aware workload management technique for embedded GPUs. The proposed technique considers the process variation and the current aging status together, and assigns a different number of instructions to clusters to minimize the aging effect in the presence of process variation. Results show that our technique improves the GPU aging in over 95 percent of cases whereas the state-of-the-art compiler-based technique improves the GPU aging in 72.25 percent of cases. Moreover, compared to the compiler-based technique, our technique reduces the performance overhead by 40 percent while achieving almost the same GPU aging improvement.
Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which ...impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.
(syn.
) is the only
species that infects humans and most other mammals. Wild boars are a reservoir of many viruses, bacteria, and parasites that can be transmitted to livestock and humans. This study ...examined the infection rate of
in wild boars and confirmed its specificity by comparing assemblages through PCR amplification of the 18S rRNA,
, and β-giardin genes. Fecal samples were collected from roadkilled or trapped wild boars from April 2016 to December 2021 in Korea. DNA was extracted directly from 612 wild boar fecal specimens using a commercial kit. PCR was performed targeting the 18S rRNA region, β-giardin, and glutamate dehydrogenase genes of
Some PCR-positive samples were selected for sequencing analysis. The obtained sequences were subsequently used for phylogenetic tree construction. Of the 612 samples tested, 125 (20.4%) were positive for
The highest infection rate was detected in the central region (12.0%) and in autumn (12.7%). Among the risk factors, the seasonal factor was statistically significant (
= 0.012). Phylogenetic analysis revealed three genetic assemblages: A, B, and E. Assemblages A and B exhibited 100% identity with
sequences isolated from human and farmed pigs in Korea and Japan. This result cannot be ignored because it indicates the possibility of zoonotic transmission. Therefore, continuous management and monitoring of this pathogen are necessary to prevent transmission and protect animal and human health.
We characterized the therapeutic biological modes of action of several terpenes in
F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced ...transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds.
Nonalcoholic steatohepatitis (NASH) is an advanced stage of fatty liver disease characterized by liver damage, inflammation, and fibrosis. Although neutrophil infiltration is consistently observed in ...the livers of patients with NASH, the precise role of neutrophil-recruiting chemokines and infiltrating neutrophils in NASH pathogenesis remains poorly understood. Here, we aimed to elucidate the role of neutrophil infiltration in the transition from fatty liver to NASH by examining hepatic overexpression of interleukin-8 (IL8), a major chemokine responsible for neutrophil recruitment in humans. Mice fed a high-fat diet (HFD) for 3 months developed fatty liver without concurrent liver damage, inflammation, and fibrosis. Subsequent infection with an adenovirus overexpressing human IL8 for an additional 2 weeks increased IL8 levels, neutrophil infiltration, and liver injury in mice. Mechanistically, IL8-induced liver injury was associated with the upregulation of components of the NADPH oxidase 2 complex, which participate in neutrophil oxidative burst. IL8-driven neutrophil infiltration promoted macrophage aggregate formation and upregulated the expression of chemokines and inflammatory cytokines. Notably, IL8 overexpression amplified factors associated with fibrosis, including collagen deposition and hepatic stellate cell activation, in HFD-fed mice. Collectively, hepatic overexpression of human IL8 promotes neutrophil infiltration and fatty liver progression to NASH in HFD-fed mice.
Drug repositioning is an attractive alternative to conventional drug development when new beneficial effects of old drugs are clinically validated because pharmacokinetic and safety profiles are ...generally already available. Since ~ 30% of drugs newly approved by the US food and drug administration (FDA) are developed through drug repositioning, identifying novel usage for existing drugs is an emerging strategy for developing disease treatments. With advances in next-generation sequencing technologies, available transcriptome data related to diseases have expanded rapidly. Harnessing these resources enables a better understanding of disease mechanisms and drug mode of action (MOA), and moves toward personalized pharmacotherapy. In this review, we briefly outline publicly available large-scale transcriptome databases and tools for drug repositioning. We also highlight recent approaches leading to the discovery of novel drug targets, drug response biomarkers, drug indications, and drug MOA.
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