研究成果

Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cellular context, and stress levels. Accumulating evidence demonstrates that an imbalance in mitochondrial dynamics leads to death in numerous types of human cancer cells. Therefore, modulating mitochondrial dynamics could be a therapeutic target. In this review, we provide an overview of the protein interaction networks involved in mitochondrial dynamics as effective and feasible drug targets and discuss the related potential therapeutic strategies...

Hepatocellular carcinoma (HCC) is characterized by rapid growth, early vascular invasion, and high metastasis. Currently available US Food and Drug Administration (FDA)-approved drugs show low therapeutic efficacy, limiting HCC treatment to chemotherapy. We designed and synthesized a novel small molecule, SCT-1015, that allosterically activated adenosine monophosphate-activated protein kinase (AMPK) to suppress the aerobic glycolysis in HCC. SCT-1015 was shown to bind the AMPK α and β-subunit interface, thereby exposing the kinase α domain to the upstream kinases, resulting in the increased AMPK activity. SCT-1015 dramatically reduced HCC cell growth in vitro and tumor growth in vivo. We further found that AMPK formed protein complexes with hypoxia-inducible factor 1-alpha (HIF1α) and...

Depilatory laser targeting melanin has been widely applied for the treatment of hypertrichosis. Both selective photothermolysis and thermal diffusion have been proposed for its effect, but the exact mechanism of permanent hair reduction remains unclear. In this study, we explore the role of thermal diffusion in depilatory laser-induced permanent hair loss and determine whether nonpigmented cells are injured by thermal diffusion. C57BL/6 mice in anagen and telogen were treated with alexandrite laser (wavelength 755 nm, pulse duration 3 milliseconds, fluence 12 J/cm2 , spot size 12 mm), respectively. Histological analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and transmission electron microscopic imaging were employed to evaluate the injury to hair follicle (...

LEOPARD syndrome (OMIM #151100), also referred to as Noonan syndrome with multiple lentigines, is characterised by various congenital defects, including Lentigines, Electrocardiographic conduction (or other cardiac) abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retarded growth and Deafness. The disease is inherited in an autosomal dominant manner, with the pathogenic variant either inherited from an affected parent or occurring de novo in a patient without any family history. Sensorineural hearing impairment (SNHI), ranging from mild to profound in severity, has been documented in approximately 15%–20% of patients with LEOPARD syndrome.1 There still is inadequate literature regarding the surgical indications and postoperative outcomes of cochlear...

Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). A genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P = 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3%...

Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase six knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotation based on ImmGen database. Composition assessments found that D6KO-derived intestinal leukocytes tend to stay inactivate or immature status. The enrichment analysis showed that D6KO-derived intestinal leukocytes are less sensitive to microbes. The mod PhEA phenotypic analysis showed that the D6KO leukocytes may link to not only immune-associated but also diverse previously non-immune-related diseases. Integrating our dataset with the...

We consider a resource allocation and offloading decision-making problem in a mobile edge computing (MEC) network. Since the locations of user equipments (UEs) vary over time in practice, we consider a dynamic network, where the UEs could leave or join the network coverage at any location. Since the joint offloading decision that minimizes the network cost also varies with the topology, the expected best offloading decision for the previous topology would not match the new topology. Consequently, the system suffers from recurring cost peaks due to the topology change. Thus, we propose a robust distributed hierarchical online learning approach to enhance the algorithm’s robustness and reduce the cost peaks. Specifically, the UEs learn the utility of each offloading decision via deep Q...

The hourglass model is a popular evo-devo model depicting that the developmental constraints in the middle of a developmental process are higher, and hence the phenotypes are evolutionarily more conserved, than those that occur in early and late ontogeny stages. Although this model has been supported by studies analyzing developmental gene expression data, the evolutionary explanation and molecular mechanism behind this phenomenon are not fully understood yet. To approach this problem, Raff proposed a hypothesis and claimed that higher interconnectivity among elements in an organism during organogenesis resulted in the larger constraints at the mid-developmental stage. By employing stochastic network analysis and gene-set pathway analysis, we aim to demonstrate such changes of...

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding...

Glucocorticoid-remediable aldosteronism (GRA) is a form of heritable hypertension caused by a chimeric fusion resulting from unequal crossing over between 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), which are two genes with similar sequences. Different crossover patterns of the CYP11B1 and CYP11B2 chimeric genes may be associated with a variety of clinical presentations. It is therefore necessary to develop an efficient approach for identifying the differences between the hybrid genes of a patient with GRA. We developed a long-read analysis pipeline named GRAde (GRA deciphering), which utilizes the nonidentical bases in the CYP11B1 and CYP11B2 genomic sequences to identify and visualize the chimeric form. We sequenced the polymerase chain reaction (PCR) products of the...