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Artificial Intelligence (AI) will not just change our lives but bring about revolutionary transformation. AI can augment efficiencies of good and bad things and thus has been considered both an opportunity and risk for the sustainable development of humans. This study designed a survey to collect 1018 samples of educated people with access to the internet in Taiwan regarding their perceptions of AI and its connections to the Sustainable Development Goals (SDGs). The respondents showed high confidence in their AI knowledge. They had a very positive attitude toward AI but at the same time thought AI was risky. In general, people in Taiwan could be “rational optimists” regarding AI. We also examined how people think of the linkages between AI and the SDGs and found that SDG 4, SDG 9, and SDG 3 had the highest “synergy” and lowest rates of “trade-off”. Significant differences for some key questions were also identified concerning the demographic variables such as gender, age, education, and college major. According to the data analysis, education played as the base to construct a sustainable AI-aided town with an embedded innovative circular economy and high-quality water and energy services, making the residents live healthier lives. The findings of this study can be referred to when the perceptions of AI and sustainability issues are of interest for an emerging high-tech economy such as Taiwan and other Asian countries.

Zika virus (ZIKV) of the flaviviridae family, is the cause of emerging infections characterized by fever, Guillain-Barré syndrome (GBS) in adults and microcephaly in newborns. There exists an urgent unmet clinical need for anti-ZIKV drugs for the treatment of infected individuals. In the current work, we aimed at the promising virus drug target, ZIKV NS3 protease and constructed a Pharmacophore Anchor (PA) model for the active site. The PA model reveals a total of 12 anchors (E, H, V) mapped across the active site subpockets. We further identified five of these anchors to be critical core anchors (CEH1, CH3, CH7, CV1, CV3) conserved across flaviviral proteases. The ZIKV protease PA model was then applied in anchor-enhanced virtual screening yielding 14 potential antiviral candidates, which were tested by in vitro assays. We discovered FDA drugs Asunaprevir and Simeprevir to have potent anti-ZIKV activities with EC 50 values 4.7 µM and 0.4 µM, inhibiting the viral protease with IC 50 values 6.0 µM and 2.6 µM respectively. Additionally, the PA model anchors aided in the exploration of inhibitor binding mechanisms. In conclusion, our PA model serves as a promising guide map for ZIKV protease targeted drug discovery and the identified ‘previr’ FDA drugs are promising for anti-ZIKV treatments.

Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A . albopictus mosquitoes. The incidence of DENV infection has been gradually increasing in recent years due to global urbanization and international travel. Understanding the virulence determinants in host and vector transmissibility of emerging epidemic DENV will be critical to combat potential outbreaks. The DENV serotype 2 (DENV-2), which caused a widespread outbreak in Taiwan in 2015 (TW2015), is of the Cosmopolitan genotype and is phylogenetically related to the virus strain linked to another large outbreak in Indonesia in 2015. We found that the TW2015 virus was highly virulent in type I and type II interferon-deficient mice, with robust replication in spleen, lung, and intestine. The TW2015 virus also had high transmissibility to Aedes mosquitoes and could be effectively spread in a continuous mosquitoes-mouse-mosquitoes-mouse transmission cycle. By making 16681-based mutants carrying different segments of the TW2015 virus, we identified the structural pre-membrane (prM) and envelope (E) genes as key virulence determinants in the host, with involvement in the high transmissibility of the TW2015 virus in mosquitoes. The transmission mouse model will make a useful platform for evaluation of DENV with high epidemic potential and development of new strategies against dengue outbreaks.

Background Rapid and accurate viral detection is essential for clinical diagnosis and effective outbreak surveillance. Traditional methods, including culture-based isolation and antigen tests, are time-consuming and limited by tissue tropism. Multiplex PCR panels, although faster, are constrained by predefined targets, limiting their ability to detect novel or unexpected viral strains. Methods We applied Oxford Nanopore Technology sequencing (ONT-Seq), a long-read, real-time, and multiplex metagenomic platform, to 85 clinical specimens using a sequence-independent, single-primer amplification (SISPA) workflow. Sequencing results were compared with routine clinical diagnostics for concordance and for identification of co-infections Results ONT-Seq achieved 80% concordance with clinical diagnostics and identified co-infections in 7% of cases missed by routine testing, including influenza C virus (ICV), and Sapporovirus. Among 58 adenovirus-positive cases, 31 samples with over 80% genome coverage at 20× depth were used for phylogenetic analysis, revealing adenovirus B3 as the predominant circulating strain. Conclusions ONT-based metagenomic sequencing enhances the detection of both known and emerging viruses in clinical specimens. Its ability to provide real-time, unbiased data supports its utility in improving diagnostic accuracy and viral surveillance. Clinical Trial Not applicable.

Transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in regulating the expression of genes participating in cellular defense mechanisms against oxidative or xenobiotic insults. However, there is increasing evidence showing that hyperactivation of NRF2 is associated with chemoresistance in several cancers, including hepatocellular carcinoma (HCC), thus making NRF2 an attractive target for cancer therapy. Another important issue in cancer medication is the adverse effects of these substances on normal cells. Here, we attempted to identify a dual-selective NRF2 regulator that exerts opposite effects on NRF2-hyperactivated HCC cells and normal keratinocytes. An antioxidant response element driven luciferase reporter assay was established in Huh7 and HaCaT cells as high-throughput screening platforms. Screening of 3,000 crude extracts from the Taiwanese Indigenous Plant Extract Library resulted in the identification of Beilschmiedia tsangii (BT) root extract as a dual-selective NRF2 regulator. Multiple compounds were found to contribute to the dual-selective effects of BT extract on NRF2 signaling in two cell lines. BT extract reduced NRF2 protein level and target gene expression levels in Huh7 cells but increased them in HaCaT cells. Furthermore, notable combinatory cytotoxic effects of BT extract and sorafenib on Huh7 cells were observed. On the contrary, sorafenib-induced inflammatory reactions in HaCaT cells were reduced by BT extract. In conclusion, our results suggest that the combination of a selective NRF2 activator and inhibitor could be a practical strategy for fine-tuning NRF2 activity for better cancer treatment and that plant extracts or partially purified fractions could be a promising source for the discovery of dual-selective NRF2 regulators.

Zika virus (ZIKV) is primarily transmitted by Aedes mosquitoes in the subgenus Stegomyia but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (Stat1-/-) were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in Stat1-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to Stat1-/- mice back to mosquitoes and then to naïve Stat1-/- mice. The 50% mosquito infectious dose of viremic Stat1-/- mouse blood was close to 810 focus-forming units (ffu)/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.

Background The role of interleukin (IL) 17A in chronic liver diseases had been extensively studied, but the function of IL-17F, which shares a high degree of homology with IL-17A, in the progression of chronic hepatic diseases is poorly understood. The aim of the study was to evaluate the association between IL-17F and liver diseases including, fibrosis and hepatocellular carcinoma (HCC). Methods Hepatic tumor samples from both hepatitis C virus (HCV) positive and negative patients (without HBV and HCV, NBNC) were examined with quantitative PCR and immunohistochemistry staining for inflammatory cytokine genes expression. In addition, 250 HCV patients naïve for interferon treatment were also subjected to enzyme-linked immunosorbent Assay (ELISA) for their serum cytokine concentrations. Results Serum IL-17F concentrations were significantly elevated in HCV patients with severe fibrosis stages. In accordance with serum data, IL-17F expression was also found higher in HCV-associated HCC tissues compared with NBNC HCC tissues at both the mRNA and protein levels. Conclusions Our data suggest that IL-17F might be used as a valuable biological marker than IL-17A during chronic fibrosis progression and HCC development in HCV patients.

An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8 + T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.

Pharmacological inhibition of cGAS-STING-controlled innate immune pathway is an emerging therapeutic strategy for a myriad of inflammatory diseases, including autoimmune disease, ulcerative colitis, non-alcoholic fatty liver disease and aging-related neurodegeneration. Here we report GHN105 as an orally bioavailable covalent STING inhibitor. Late-stage diversification of the briarane-type diterpenoid excavatolide B allowed the installation of solubility-enhancing functional groups while enhancing its activity as a covalent STING inhibitor against multiple human STING variants, including the S154 variant responsible for a genetic autoimmune disease. Selectively engaging the membrane-proximal Cys91 residue of STING, GHN105 dose-dependently inhibited cGAS-STING signaling and type I interferon responses in cells and in vivo. Orally administered GHN105 exerted marked therapeutic efficacy and reversed key pathological features in a delayed-treatment acute colitis mouse model. Notably, we also showed that GHN105 covalently engaged STING in the colon tissues. Our study provided proof of concept that synthetic briarane analog GHN105 serves as a safe and orally active covalent STING inhibitor. With a growing number of chronic inflammatory diseases linked to aberrant STING activation, orally bioavailable STING inhibitors would benefit patients by lowering the infection risk from frequent injections while allowing long-term systemic administration.