研究成果

Toxoplasmosis, caused by Toxoplasma gondii, poses risks to vulnerable populations. TgPDCD5, a secreted protein of T. gondii, induces apoptosis through heparan sulfate-mediated endocytosis. The entry mechanism of TgPDCD5 has remained elusive. Here, we present the solution structure of TgPDCD5 as a helical bundle with an extended N-terminal helix, exhibiting molten globule characteristics. NMR perturbation studies reveal heparin/heparan sulfate binding involving the heparan sulfate/heparin proteoglycans-binding motif and the core region, influenced by proline isomerization of P107 residue. The heterogeneous proline recruits a cyclophilin TgCyp18, accelerating interconversion between conformers and regulating heparan/heparin binding. These atomic-level insights elucidate the binary switch...

Background: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. Results:...

Human adipose-derived stem cells (ASCs) have shown immense potential for regenerative medicine. Our previous work demonstrated that chitosan nano-deposited surfaces induce spheroid formation and differentiation of ASCs for treating sciatic nerve injuries. However, the underlying cell fate and differentiation mechanisms of ASC-derived spheroids remain unknown. Here, we investigate the epigenetic regulation and signaling coordination of these therapeutic spheroids. During spheroid formation, we observed significant increases in histone 3 trimethylation at lysine 4 (H3K4me3), lysine 9 (H3K9me3), and lysine 27 (H3K27me3), accompanied by increased histone deacetylase (HDAC) activities and decreased histone acetyltransferase activities. Additionally, HDAC5 translocated from the cytoplasm to the...

Briefly (10 min) exposing C2C12 myotubes to low amplitude (1.5 mT) pulsed electromagnetic fields (PEMFs) generated a conditioned media (pCM) that was capable of mitigating breast cancer cell growth, migration, and invasiveness in vitro, whereas the conditioned media harvested from unexposed myotubes, representing constitutively released secretome (cCM), was less effective. Administering pCM to breast cancer microtumors engrafted onto the chorioallantoic membrane of chicken eggs reduced tumor volume and vascularity. Blood serum collected from PEMF-exposed or exercised mice allayed breast cancer cell growth, migration, and invasiveness. A secretome preconditioning methodology is presented that accentuates the graded anticancer potencies of both the cCM and pCM harvested from myotubes,...

In this paper, we explore the challenges associated with biomarker identification for diagnosis purpose in biomedical experiments, and propose a novel approach to handle the above challenging scenario via the generalization of the Dantzig selector. To improve the efficiency of the regularization method, we introduce a transformation from an inherent nonlinear programming due to its nonlinear link function into a linear programming framework under a reasonable assumption on the logistic probability range. We illustrate the use of our method on an experiment with binary response, showing superior performance on biomarker identification studies when compared to their conventional analysis. Our proposed method does not merely serve as a variable/biomarker selection tool, its ranking of...

Purpose: The purpose of this study is to find essential risk factors associated with liver function (LF) deteriorations within fluctuating long-term LF and their time-varying effects in patients with hepatocellular carcinoma (HCC) receiving hepatic radiotherapy and to identify high-risk groups for adverse LF deteriorations and their changes over time in facilitating the prevention of hepatic decompensation and the improvement of survival. Materials and methods: A total of 133 HCC patients treated by hepatic radiotherapy were enrolled. A study design was conducted to convert posttreatment long-term LF with fluctuating levels over time to recurrent LF events using defined upgrades in a grading scale. The hazard ratios (HR) of pretreatment biochemical, demographic, clinical, and dosimetric...

Efficient clearance of dead cells is critical for tissue regeneration after injuries. How dead cells are removed from the skin after radiotherapy and chemotherapy is unclear. In this study, we found that radiotherapeutic and chemotherapeutic damage induced extensive apoptosis of highly proliferative transit-amplifying cells in hair follicles. These apoptotic cells disappeared rapidly in the early stage of regenerative attempts, and the lost structures were regenerated with transient and low-level inflammation. Without the recruitment of macrophages as scavengers, the dying cells were engulfed directly by adjacent surviving transit-amplifying cells, which produced mature phagosomes through fusion with lysosomes in a manner similar to professional phagocytosis and remained active in...

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19. Significant differentially expressed...

Introduction: The Swarm Intelligence Based (SIB) method has widely been applied to efficient optimization in many fields with discrete solution domains. E-commerce raises the importance of designing suitable selling strategies, including channel- and direct sales, and the mix of them, but researchers in this field seldom employ advanced metaheuristic techniques in their optimization problem due to the complexities caused by the high-dimensional problems and cross-dimensional constraints. Method: In this work, we introduce an extension of the SIB method that can simultaneously tackle these two challenges. To pursue faster computing, CPU parallelization techniques are employed for algorithm acceleration. Results: The performance of the SIB method is examined on the problems of designing...

Aberrant DNA/RNA hybrids (R-loops) formed during transcription and replication disturbances pose threats to genome stability. DHX9 is an RNA helicase involved in R-loop resolution, but how DHX9 is regulated in response to genotoxic stress remains unclear. Here we report that DHX9 is phosphorylated at S321 and S688, with S321 phosphorylation primarily induced by ATR after DNA damage. Phosphorylation of DHX9 at S321 promotes its interaction with γH2AX, BRCA1 and RPA, and is required for its association with R-loops under genotoxic stress. Inhibition of ATR or expression of the non-phosphorylatable DHX9S321A prevents DHX9 from interacting with RPA and R-loops, leading to the accumulation of stress-induced R-loops. Furthermore, depletion of RPA reduces the association between DHX9 and γH2AX,...