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Comprehensive survey of tick infestations and pathogen detection in Taiwanese wildlife: Uncovering public health risks
No full text[[abstract]]INTRODUCTION: Ticks are important vectors of zoonotic diseases, yet their biodiversity and pathogen associations remain understudied in many regions. This study aims to provide a comprehensive survey of tick species and associated pathogens in Taiwanese wildlife to assess their ecological roles and public health implications. METHODS: We conducted a nationwide survey across Taiwan and its affiliated islands, collecting ticks from wildlife hosts and their environments. Morphological and molecular techniques were used to identify tick species and detect tick-borne pathogens, focusing on Rickettsia spp., Ehrlichia spp. and Anaplasma spp. Bayesian phylogenetic analyses were performed to confirm pathogen identities and explore genetic relationships. RESULTS: We identified 12 tick species and 6 pathogens, including a potential novel Rickettsia species. Haemaphysalis mageshimaensis and Haemaphysalis longicornis were the most abundant, with H. longicornis recorded in Taiwan for the first time. Molecular analysis revealed widespread Rickettsia spp. infections, with detection rates reaching 100% in New Taipei City, Changhua and Yilan, and 83.33% in Lienchiang. No pathogens were detected in counties such as Yunlin, Chiayi and Tainan. Phylogenetic analysis confirmed the presence of Rickettsia tamurae, Rickettsia massiliae and Candidatus Rickettsia jingxinensis, as well as a potential novel species closely related to R. conorii subsp. raoultii. CONCLUSIONS: This study highlights the diversity of ticks and tick-borne pathogens in Taiwanese wildlife, underscoring the importance of ongoing surveillance. The first record of H. longicornis and the identification of a novel Rickettsia species demonstrate the urgent need for research on their ecological and zoonotic impact
EGFRvIII-driven microenvironmental fibroblast activation and transformation accelerate oral cancer progression via lipocalin-2/ STAT3 axis
No full text[[abstract]]Oral squamous cell carcinoma (OSCC) is an aggressive malignancy frequently characterized by dysregulated epidermal growth factor receptor (EGFR) signaling. Among EGFR mutation, EGFRvIII, an extracellular domain truncated form without exons 2-7, exhibits ligand-independent and constitutive EGFR activation. Although EGFRvIII functions as an oncogene in glioblastoma, its role in OSCC remains unclear. Here, we demonstrate that EGFRvIII is highly prevalent in OSCC, with approximately 70 % of OSCC tumor samples revealing high EGFRvIII expression. EGFRvIII enhances metastatic and proliferative potential, while its knockdown significantly reduces these malignant phenotypes. Beyond its direct oncogenic effects, EGFRvIII actively remodels the tumor microenvironment (TME) by recruiting and activating fibroblasts. In both xenograft models and co-culture systems, OSCC cells expressing EGFRvIII stimulated the expression of fibroblast activation markers-including alpha-smooth muscle actin (alpha-SMA), platelet-derived growth factor receptors (PDGFRA/PDGFRB), and collagen-thereby promoting a tumor-supportive stroma. Moreover, RNA sequencing and cytokine array analyses revealed that EGFRvIII induces lipocalin-2 (LCN2) expression and secretion. Elevated LCN2 in the conditioned medium from OSCC-EGFRvIII cells further stimulates fibroblast activation via the STAT3 signaling pathway, as pharmacological inhibition of STAT3 attenuates LCN2 -driven fibroblast activation. Furthermore, exposure to environmental carcinogens such as nicotine-derived nitrosamine ketone (NNK) and arecoline enhances EGFRvIII expression and downstream signaling, exacerbating tumor aggressiveness. These findings reveal a positive feedback loop in which EGFRvIII fosters OSCC progression by stimulating LCN2-STAT3-mediated fibroblast activation. Targeting EGFRvIII and its downstream effectors may therefore represent a promising strategy to mitigate OSCC progression and improve therapeutic outcomes
Severe enterovirus A71 pathogenesis and immune responses in human nucleolin transgenic mice
No full text[[abstract]]Enterovirus A71 (EV-A71) infection is known to cause hand-foot-mouth disease, which may develop severe symptoms such as encephalitis, herpangina, and paralysis, leading to pulmonary edema and even death in children under five years old. Existing animal models for EV-A71 pathogenesis have limitations, necessitating novel models to study human-relevant disease mechanisms. Using glycoproteomic profiling to identify EV-A71-interacting proteins, we previously discovered human nucleolin (hNCL) as an attachment molecule that enhances viral binding and infection in vitro. Here, we developed human nucleolin transgenic (hNCL-Tg) mice to investigate EV-A71 pathogenesis in vivo. Compared to wild-type (WT) mice, EV-A71-infected hNCL-Tg mice exhibited higher clinical scores, progressive limb paralysis, and increased mortality. Six days post-infection, hNCL-Tg mice showed elevated viral loads in the spinal cord and skeletal muscle, with pronounced EV-A71 VP1 expression in these tissues and the brainstem. Histopathology revealed severe skeletal muscle damage and significant pulmonary edema, characterized by lung congestion, hemorrhage, and erythrocyte infiltration into alveoli. Infected hNCL-Tg mice also displayed elevated levels of encephalitis- and pulmonary edema-associated proinflammatory cytokines (IL-1 beta, IL-6, IL-13). These findings establish the hNCL-Tg mouse as a robust model for studying EV-A71 pathogenesis and evaluating preclinical therapeutics
Wireless chargeable gold Yarnball-mediated mitochondrial depolarization for dendritic cell detainment in programmed brain tumor immunotherapy
No full text[[abstract]]Activation of the innate immune cascade offers a potential strategy to inhibit glioblastoma (GBM) proliferation. However, immune privilege along with blood-brain barrier (BBB) and low immunogenicity of GBM often limits lymphocyte infiltration. In this study, a wireless charging mitochondria-targeted nanoantenna (WINA) served as a membrane-disrupting and mitochondria-depolarizing agent was developed for interning dendritic cells and a programmed immunotherapy. By convection-enhanced delivery, membrane-disrupting cationic triphenylphosphine (TPP)-conjugated polyglutathione (pGSH) on WINA improves tumor penetration to deep area and targets mitochondria. Under high-frequency magnetic field (HFMF) irradiation, WINA generates reactive oxygen species (ROS) from hydrogen peroxide (H2O2) in mitochondria and drives mitochondrial depolarization through eddy current generation. The depolarization further causes the dissipation of mitochondrial membrane potential (MMP), leading to the release of damage-associated molecular patterns (DAMPs). This process activates dendritic cells, thereby enhancing the effective infiltration of T cells to the brain tumor. Furthermore, transcriptome analysis of brain tumors revealed that key genes such as Cd8a, Ifng, Tnf, and Il1b, which are critical for T cell activation. In whole-brain diffusion MRI, fiber tracing of the M1-TH and S1HL-Cpu tracts was explored after treatment, indicating improved brain function. Combined with immune checkpoint therapy, this approach resulted in antitumor activity and tumor growth inhibition
Cross-correlation analysis of monthly Google search volume and suicide in Taiwan, 2012–2022
No full text[[abstract]]Background: The present study investigated the 1-month, 2-month, and 3-month prospective associations of Google search terms with suicide in Taiwan from 2012 to 2022. Methods: We analyzed daily suicide data from Taiwan’s Cause of Death Statistics between January 1, 2012, and December 31, 2022. Data on Google search volumes for 37 terms related to suicide-related, socioeconomic status, familial problems, and physical and psychiatric problems were extracted from Google Trends. Cross-correlation coefficients between monthly Google search term volumes and monthly suicide were calculated at lags of 3 months (lag-3), 2 months (lag-2), and 1 month (lag-1). Results: The monthly Google search volumes of two terms, “pain” and “Taiwan economy”, positively predicted monthly suicide in the total population. The search term “hypnotic” lag-3 negatively correlated with monthly suicide in the population aged ≥65. The search term “allergy” lag-1 positively correlated with monthly suicide in the population aged ≥65. Conclusions: The monthly Google search terms of “pain” and “Taiwan economy” positively correlated with monthly suicide. The search terms “hypnotic” and “allergy” negatively and positively correlated with monthly suicide in the population aged ≥65, respectively. These terms may enable more accurate forecasting of future suicides
Cerium-doped calcium carbonate microparticles combined with low-intensity ultrasound for efficient sonodynamic therapy in body sculpting
No full text[[abstract]]Excessive caloric intake and reduced energy expenditure contribute to obesity and localized fat accumulation, adversely affecting overall health. Despite advancements in obesity treatments, noninvasive approaches for targeted fat reduction remain limited. This study introduces a novel sonosensitizer microparticle, cerium-doped calcium carbonate (CaCO(3):Ce), and evaluates its potential application in combination with low-intensity ultrasound (LIUS) for noninvasive body sculpting. CaCO(3):Ce was synthesized via an environmentally friendly method, producing uniform 1.77 μm particles optimized for endocytosis. Energy-dispersive X-ray and X-ray photoelectron spectroscopy confirmed successful cerium doping. The particles demonstrated excellent biocompatibility and generated reactive oxygen species under LIUS exposure. Safety was validated through biochemical, hematological, and histological analyses in Sprague-Dawley rats. Animal experiments further revealed that CaCO(3):Ce combined with ultrasound significantly reduced body weight growth rates, waistline measurements, and subcutaneous fat accumulation. These findings suggest that CaCO(3):Ce, coupled with LIUS, offers a promising, noninvasive, and low-risk strategy for body sculpting, addressing limitations of current methodologies
A novel immunogen comprising a bc loop and mutant fusion loop epitopes generates potent neutralization and protective abilities against flaviviruses without risk of disease enhancement
No full text[[abstract]]Flaviviruses, including Dengue virus (DENV), Zika virus (ZIKV) and Japanese encephalitis virus (JEV), remain major global health threats, and currently, there are no widely available vaccines for humans. The fusion loop region of the flavivirus envelope protein plays a crucial role in eliciting neutralizing antibodies and providing protection against secondary DENV infections. However, these antibodies often exhibit dual functionalities, with both neutralizing and enhancing activities, posing a challenge for vaccine development. In this study, we focused on optimizing the fusion loop epitope as the primary immunogen and incorporated the adjacent bc loop which we had reported previously as a complementary element, aiming to enhance the immunogen capable of robust neutralization and protection without inducing the risk of antibody-dependent enhancement (ADE). This newly designed immunogen was named as muBCFL which comprises sequences spanning from amino acid 69 to 116 primarily on DENV-2 envelope protein, along with four specific mutations (T76A, W101A, G106Q, and L107D). The synthesized muBCFL peptide elicited neutralizing antibodies against all four DENV serotypes, ZIKV, and JEV, with particularly strong neutralization activity against DENV-2, ZIKV, and JEV. Besides, compared to pre-immune sera, muBCFL-immune sera significantly reduced viremia levels in DENV- or ZIKV-infected AG129 mice and increased the survival rates of JEV-challenged ICR mice. Furthermore, in vitro and in vivo ADE assays validated that muBCFL-immune sera did not induce ADE compared with the control 4G2 monoclonal antibody. These findings indicated that the muBCFL sequence holds great potential as a safe and effective immunogen for developing a flavivirus vaccine in the future
[[alternative]]Immunosuppressive cells and methods of making and using thereof
No full text[[abstract]]This invention relates to an immunosuppressive cell, and methods of obtaining the cell and using the cell. The immunosuppressive cell is obtained by culturing a precursor cell in a medium that contains a GRO chemokine
[[alternative]]Multiple mosquito-borne flavivirus vaccine and use thereof in inducing neutralizing antibodies
No full text[[abstract]]本發明係關於一種胜肽免疫原，其包含至少一段複製的胺基酸序列：RCPTTGE(命名為JBP)，本發明之胜肽免疫原可誘發有效對抗二或多種蚊媒黃病毒的免疫反應。本發明亦提供單/多價病毒疫苗以保護動物免受蚊媒黃病毒感染，包括日本腦炎病毒(JEV)、西尼羅病毒(WNV)、登革熱病毒(DENV)與茲卡病毒(ZIKE)的感染
[[alternative]]Method for absolute quantification of target molecule having an amine group
No full text[[abstract]]本發明提供一種具有胺基團的目標分子的絕對定量方法，特別是針對胜肽或蛋白質