Several epidemiological studies have suggested that exposure to arsenic is strongly correlated with the development of cardiovascular diseases such as hypertension. To determine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on vasorelaxation using isolated rat aortic rings in an organ-bath system. Treatment with arsenite inhibited acetylcholine-induced relaxation of the aortic rings in a concentration-dependent manner, whereas several other arsenic species did not have any effect. Consistent with these findings, the levels of guanosine 3',5'-cyclic monophosphate (cGMP) in the aortic rings were significantly reduced by arsenite treatment. In cultured human aortic endothelial cells, treatment with arsenite resulted in a concentration-dependent inhibition of endothelial nitric oxide synthase (eNOS). In addition, higher concentrations of arsenite decreased the relaxation induced by sodium nitroprusside (an NO donor) and 8-Br-cGMP (a cGMP analog) in aortic rings without endothelium. These in vitro results indicate that arsenite is capable of suppressing relaxation in blood vessels by inhibiting eNOS activity in endothelial cells and by impairing the relaxation machinery in smooth muscle cells. In vivo studies revealed that the reduction of blood pressure by acetylcholine infusion was significantly suppressed after arsenite was administered intravenously to rats. These data suggest that an impairment of vasomotor tone due to arsenite exposure may be a contributing factor in the development of cardiovascular disease.

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Stabilizing atomically dispersed single atoms (SAs) on silicon photoanodes for photoelectrochemical-oxygen evolution reaction is still challenging due to the scarcity of anchoring sites. Here, we elaborately demonstrate the decoration of iridium SAs on silicon photoanodes and assess the role of SAs on the separation and transfer of photogenerated charge carriers. NiO/Ni thin film, an active and highly stable catalyst, is capable of embedding the iridium SAs in its lattices by locally modifying the electronic structure. The isolated iridium SAs enable the effective photogenerated charge transport by suppressing the charge recombination and lower the thermodynamic energy barrier in the potential-determining step. The Ir SAs/NiO/Ni/ZrO2/n-Si photoanode exhibits a benchmarking photoelectrochemical performance with a high photocurrent density of 27.7 mA cm−2 at 1.23 V vs. reversible hydrogen electrode and 130 h stability. This study proposes the rational design of SAs on silicon photoelectrodes and reveals the potential of the iridium SAs to boost photogenerated charge carrier kinetics.

This study investigated the efficacy of Toxoplasma GRA16, which binds to herpes virus‐associated ubiquitin‐specific protease (HAUSP), in anticancer treatment, and whether the expression of GRA16 in genetically modified hepatocellular carcinoma (HCC) cells (GRA16‐p53‐wild HepG2 and GRA16‐p53‐null Hep3B) regulates PTEN because alterations in phosphatase and tensin homologue (PTEN) and p53 are vital in liver carcinogenesis and the abnormal p53 gene appears in HCC. For this purpose, we established the GRA16 cell lines using the pBABE retrovirus system, assessed the detailed mechanism of PTEN regulation in vitro and established the anticancer effect in xenograft mice. Our study showed that cell proliferation, antiapoptotic factors, p‐AKT/AKT ratio, cell migration and invasive activity were decreased in GRA16‐stable HepG2 cells. Conversely, the apoptotic factors PTEN and p53 and apoptotic cells were elevated in GRA16‐stable HepG2 cells but not in Hep3B cells. The change in MDM2 was inconspicuous in both HepG2 and Hep3B; however, the PTEN level was remarkably elevated in HepG2 but not in Hep3B. HAUSP‐bound GRA16 preferentially increased p53 stabilization by the nuclear localization of PTEN rather than MDM2‐dependent mechanisms. These molecular changes appeared to correlate with the decreased tumour mass in GRA16‐stable‐HepG2 cell‐xenograft nude mice. This study establishes that GRA16 is a HAUSP inhibitor that targets the nuclear localization of PTEN and induces the anticancer effect in a p53‐dependent manner. The efficacy of GRA16 could be newly highlighted in HCC treatment in a p53‐dependent manner.

Background Tuberculosis (TB) is a highly infectious disease. Negative perceptions and insufficient knowledge have made its eradication difficult. Recently, mobile health care interventions, such as an anti-TB chatbot developed by the research team, have emerged in support of TB eradication programs. However, before the anti-TB chatbot is deployed, it is important to understand the factors that predict its acceptance by the population. Objective This study aims to explore the acceptance of an anti-TB chatbot that provides information about the disease and its treatment to people vulnerable to TB in South Korea. Thus, we are investigating the factors that predict technology acceptance through qualitative research based on the interviews of patients with TB and homeless facility personnel. We are then verifying the extended Technology Acceptance Model (TAM) and predicting the factors associated with the acceptance of the chatbot. Methods In study 1, we conducted interviews with potential chatbot users to extract the factors that predict user acceptance and constructed a conceptual framework based on the TAM. In total, 16 interviews with patients with TB and one focus group interview with 10 experts on TB were conducted. In study 2, we conducted surveys of potential chatbot users to validate the extended TAM. Survey participants were recruited among late-stage patients in TB facilities and members of web-based communities sharing TB information. A total of 123 responses were collected. Results The results indicate that perceived ease of use and social influence were significantly predictive of perceived usefulness (P=.04 and P<.001, respectively). Perceived usefulness was predictive of the attitude toward the chatbot (P<.001), whereas perceived ease of use (P=.88) was not. Behavioral intention was positively predicted by attitude toward the chatbot and facilitating conditions (P<.001 and P=.03, respectively). The research model explained 55.4% of the variance in the use of anti-TB chatbots. The moderating effect of TB history was found in the relationship between attitude toward the chatbot and behavioral intention (P=.01) and between facilitating conditions and behavioral intention (P=.02). Conclusions This study can be used to inform future design of anti-TB chatbots and highlight the importance of services and the environment that empower people to use the technology.