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Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1–4 infection in vitro. RT-qPCR analysis of HCQ-treated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-β, AP-1, and NFκB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-κB kinase ɛ (IKKɛ), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS- and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.

Background Breastfeeding benefits both mothers and infants. Even though Taiwan national policy promotes exclusive breastfeeding (EBF), the rates in Taiwan are below those in other developed countries. This study aimed to investigate factors associated with EBF cessation at 1 and 2 months postpartum. Methods This study was conducted in a community hospital in southern Taiwan between December 2016 and June 2017. Birth mothers ( n  = 1077) were interviewed by telephone at 1 and 2 months postpartum to collect information on infant feeding patterns (EBF since birth or not) and reasons for EBF cessation. Multivariate logistic regression models were used to determine risk factors associated with EBF cessation at 1 and 2 months. Results At 1 month, 432 participants (40.1%) maintained EBF. Factors associated with cessation were lack of tertiary education, primiparity, perceived low milk quantity, mother/infant separation, medical condition in mother, inconvenience/fatigue due to breastfeeding, and baby-centered factors. At 2 months, 316 participants (29.3%) maintained EBF. Factors associated with cessation were lack of tertiary education, primiparity, perceived low milk quantity, and return to work. Conclusions Education level, primiparity, perceived low milk quantity, and return to work are associated with premature cessation of EBF in Taiwan. Strategies about health education, family support, and baby-mother friendly environment can be used to achieve higher EBF rate.

Background The proportion of older adults and individuals with disabilities in the general population increases each year. Thus, clinical clerkships designed for physiotherapy interns should provide more than simply knowledge and skills. For such interns to be able to handle the requirements of their future jobs, clerkships must enable them to develop empathy and positive attitudes toward patients. This study investigated the effect of simulation-based, holistic health-care education on physiotherapy interns’ empathy, attitudes, and knowledge.  Methods A parallel-group design. Thirty physiotherapy interns from a medical institution were enrolled as participants, with experimental and control groups each comprising 15 participants. Both groups received standard clinical training. However, the experimental group received an additional 3.5 h of simulation-based holistic health-care education. The Jefferson Scale of Empathy, Kogan’s Attitudes Toward Old People Scale, the Attitudes Towards the Elderly Scale, the Knowledge About Aging Scale, Knowledge of the Situation of Older People Scale, Perceptions of Working with Older People Scale, and Care Willingness Scale were used in a pretest and posttest. Results After the intervention period, we observed substantial between-group differences of 6.4 points on the Jefferson Scale of Empathy ( p  = 0.001), 7.7 points on Kogan’s Attitudes Toward Old People Scale ( p  = 0.002), 3.5 points on the Attitudes Toward the Elderly Scale ( p  = 0.002), 2.5 points on Knowledge About Aging ( p  = 0.055), 4.5 points on the Knowledge of the Situation of Older People Scale ( p  < 0.001), and 2.1 points on Perceptions of Working with Older People Scale ( p  = 0.046). Conclusion Simulation-based, holistic health-care education can significantly improve the empathy, knowledge, and attitudes of physiotherapy interns.

Detection of lead(II) (Pb2+) ions in water is important for the protection of human health and environment. The growing demand for onsite detection still faces challenges for sensitive and easy-to-use methods. In this work, a novel surface plasmon resonance (SPR) biosensor based on GR-5 DNAzyme and gold nanoparticles (AuNPs) was developed. Thiolated DNAzyme was immobilized on the gold surface of the sensor chip followed by anchoring the substrate-functionalized AuNPs through the DNAzyme-substrate hybridization. The coupling between the localized surface plasmon (LSP) of AuNPs and the surface plasmon polaritons (SPP) on the gold sensor surface was used to improve the sensitivity. The substrate cleavage in the presence of Pb2+ ions was catalyzed by DNAzyme, leading to the removal of AuNPs and the diminished LSP-SPP coupling. The optimal detection limit was 80 pM for the sensor fabricated with 1 μM DNAzyme, corresponding to two or three orders of magnitude lower than the toxicity levels of Pb2+ in drinking water defined by WHO and USEPA. By tuning the surface coverage of DNAzyme, the sensitivity and dynamic range could be controlled. This sensor also featured high selectivity to Pb2+ ions and simple detection procedure. Successful detection of Pb2+ ions in groundwater indicates that this method has the prospect in the onsite detection of Pb2+ ions in water. Given the variety of AuNPs and metal-specific DNAzymes, this detection strategy would lead to the development of more sensitive and versatile heavy metal sensors.

Current liver fibrosis scoring by computer-assisted image analytics is not fully automated as it requires manual preprocessing (segmentation and feature extraction) typically based on domain knowledge in liver pathology. Deep learning-based algorithms can potentially classify these images without the need for preprocessing through learning from a large dataset of images. We investigated the performance of classification models built using a deep learning-based algorithm pre-trained using multiple sources of images to score liver fibrosis and compared them against conventional non-deep learning-based algorithms - artificial neural networks (ANN), multinomial logistic regression (MLR), support vector machines (SVM) and random forests (RF). Automated feature classification and fibrosis scoring were achieved by using a transfer learning-based deep learning network, AlexNet-Convolutional Neural Networks (CNN), with balanced area under receiver operating characteristic (AUROC) values of up to 0.85–0.95 versus ANN (AUROC of up to 0.87–1.00), MLR (AUROC of up to 0.73–1.00), SVM (AUROC of up to 0.69–0.99) and RF (AUROC of up to 0.94–0.99). Results indicate that a deep learning-based algorithm with transfer learning enables the construction of a fully automated and accurate prediction model for scoring liver fibrosis stages that is comparable to other conventional non-deep learning-based algorithms that are not fully automated.

In this study, aramid fiber (Kevlar® 29 fiber) and carbon fiber were added into concrete in a hybrid manner to enhance the static and impact mechanical properties. The coupling agent presence on the surface of carbon fibers was spotted in Scanning Electron Microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) graphs. The carbon fiber with a coupling agent affected the mechanical strength of the reinforced concrete. At 1% fiber/cement weight percentage, the hybrid fiber-reinforced concrete (HFRC) prepared using Kevlar fiber and carbon fiber of 12 and 24 mm in length under different mix proportions was investigated to determine the maximum mechanical strengths. From the test results, the mechanical strength of the HFRC attained better performance than that of the concrete with only Kevlar or carbon fibers. Foremost, the mix proportion of Kevlar/carbon fiber (50–50%) significantly improved the compressive, flexural, and splitting tensile strengths. Under different impact energies, the impact resistance of the HFRC specimen was much higher than that of the benchmark specimen, and the damage of the HFRC specimens was examined with an optical microscope to identify slippage or rupture failure of the fiber in concrete.

Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus , using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C 14 H 19 O 10 P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus .

The symmetrical Double-O-Tube (DOT) shield tunneling method, first developed in Japan in the 1980s, offers advantages in optimizing cross-sectional area and reducing construction space. While past studies have primarily focused on construction-induced settlement or empirical modeling, this study presents the first comprehensive three-dimensional seismic analysis of Taiwan’s first DOT shield tunnel, part of the CA450A contract of the Taoyuan International Airport MRT. A detailed numerical simulation is conducted using PLAXIS 3D 2024 with the Hardening Soil model, capturing both static and dynamic responses under earthquake loading. Notably, the analysis incorporates full-direction seismic input (3D) using Arias intensity-based filtering and scaling to assess the tunnel’s mechanical behavior under varying seismic intensities. Key structural responses such as displacement, axial force, shear force, and bending moment are evaluated. The findings reveal critical deformation patterns and stress concentrations in the central support structure, offering novel insights for the seismic design of complex multi-cell shield tunnels in high-risk seismic zones.

ObjectiveThe rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD.Design442 incident cases (186 Crohn's disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs.ResultsIn multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC.ConclusionsThis first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Concrete is a brittle material due to its poor tensile strength; consequently, concrete tends to crack or peel under an applied external load. Previous studies have investigated the effect of incorporating fiber into concrete, which can improve its tensile strength. In this study, the static and dynamic mechanical characteristics of three types of fiber-reinforced concrete (FRC) were examined: carbon-fiber-reinforced concrete (CFRC); Kevlar-fiber-reinforced concrete (KFRC); and a combination of both, known as carbon/Kevlar-hybrid-fiber-reinforced concrete (HFRC). This study created concrete specimens by pneumatically dispersing carbon and Kevlar fibers and mixing them with cement to comprise 1% of the weight. The mixture was then combined with aggregates and water to form the concrete specimens. When compared with the benchmark concrete specimens, it was found that the compressive strength of the CFRC, KFRC, and HFRC specimens increased by about 19% to 50%, the bending strength increase by about 8% to 32%, and the splitting strength increased by about 4% to 36%. Specifically, the HFRC made with the 24 mm carbon and Kevlar fibers displayed the most significant mechanical strength in a static state. Furthermore, the HFRC showed superior resistance to impact compared to the benchmark concrete specimens across various impact energies, with the 24 mm carbon and Kevlar fiber HFRC showing the highest resistance. The inclusion of fibers in the split Hopkinson pressure bar (SHPB) test demonstrated a notable increase in the maximum strength, particularly in the case of the 12 mm carbon fiber combined with the 24 mm Kevlar fiber in the HFRC specimen.