A cell surface receptor for thyroid hormone that activates extracellular regulated kinase (ERK) 1/2 has been identified on integrin αvβ3. We have examined the actions of thyroid hormone initiated at ...the integrin on human NCI-H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At a physiologic total hormone concentration (10(-7) M), T(4) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T(3)) at a supraphysiologic concentration. Neutralizing antibody to integrin αvβ3 and an integrin-binding Arg-Gly-Asp (RGD) peptide blocked thyroid hormone-induced PCNA expression. Tetraiodothyroacetic acid (tetrac) lacks thyroid hormone function but inhibits binding of T(4) and T(3) to the integrin receptor; tetrac eliminated thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In these estrogen receptor-α (ERα)-positive lung cancer cells, thyroid hormone (T(4)>T(3)) caused phosphorylation of ERα; the specific ERα antagonist ICI 182,780 blocked T(4)-induced, but not T(3)-induced ERK1/2 activation, as well as ERα phosphorylation, proliferating-cell nuclear antigen (PCNA) expression and hormone-dependent thymidine uptake by tumor cells. Thus, in ERα-positive human lung cancer cells, the proliferative action of thyroid hormone initiated at the plasma membrane is at least in part mediated by ERα. In summary, thyroid hormone may be one of several endogenous factors capable of supporting proliferation of lung cancer cells. Activity as an inhibitor of lung cancer cell proliferation induced at the integrin receptor makes tetrac a novel anti-proliferative agent.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
White spot syndrome virus (WSSV), an enveloped double-stranded DNA virus, is the causative agent of white spot syndrome (WSS), which has been linked to cultured shrimp mass mortality in many ...countries. Therefore, the development of anti-WSSV agents is among the top priorities of the aquaculture sector. Here, we describe the preparation of polyamine-modified carbon quantum dots (polyamine CQDs) for the treatment of WSSV. Moreover, in vivo experiments were conducted in shrimp to confirm the anti-WSSV effect of the proposed CQD-based strategy.
Metal-doping is widely used to enhance charge generation and reduce carrier recombination of BiVO4 for catalyzing water oxidation. In this work, different Mo-doping levels are applied to synthesize ...Mo-doped BiVO4 (MBVO) on conductive glasses. Molybdenum plays multiple roles of dopant, structure-confined mediator, and sources for forming additional semiconductor. The MBVO with lower Mo-doping levels presents bi-layered structure with nanowire overlayer and nanorod underlayer, which can develop facile one-dimensional charge-transfer paths and efficient heterojunction. With preferable design of nanowire and nanorod layers, the high light absorption, small charge-transfer resistance and high carrier density are attained for MBVO with 1% Mo-doping, which shows the highest photocurrent density of 2.5 mA/cm2 at 1.23 VRHE, smallest onset potential of 0.22 VRHE and highest maximum photoconversion efficiency of 2.20%. This work carefully illustrates the function of molybdenum and firstly constructs the unique bi-layered structure for MBVO to display outstanding photoelectrochemical performance for catalyzing water oxidation.
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•Varied Mo-doping levels are used to make Mo-doped BiVO4 (MBVO) as photocatalysts.•Mo acts as dopant, structure-confined mediator, and source of other semiconductor.•The MBVO with less Mo-doping shows the nanowire and nanorod bi-layered structure.•MBVO (1% Mo) shows photocurrent of 2.5 mA/cm2 and onset potential of 0.22 VRHE.•Due to facile one-dimensional charge-transfer paths and efficient heterojunction.
Early studies demonstrated that whole‐body androgen receptor (AR)–knockout mice with hypogonadism exhibit insulin resistance. However, details about the mechanisms underlying how androgen/AR ...signaling regulates insulin sensitivity in individual organs remain unclear. We therefore generated hepatic AR‐knockout (H‐AR−/y) mice and found that male H‐AR−/y mice, but not female H‐AR−/− mice, fed a high‐fat diet developed hepatic steatosis and insulin resistance, and aging male H‐AR−/y mice fed chow exhibited moderate hepatic steatosis. We hypothesized that increased hepatic steatosis in obese male H‐AR−/y mice resulted from decreased fatty acid β‐oxidation, increased de novo lipid synthesis arising from decreased PPARα, increased sterol regulatory element binding protein 1c, and associated changes in target gene expression. Reduced insulin sensitivity in fat‐fed H‐AR−/y mice was associated with decreased phosphoinositide‐3 kinase activity and increased phosphenolpyruvate carboxykinase expression and correlated with increased protein‐tyrosine phosphatase 1B expression. Conclusion: Together, our results suggest that hepatic AR may play a vital role in preventing the development of insulin resistance and hepatic steatosis. AR agonists that specifically target hepatic AR might be developed to provide a better strategy for treatment of metabolic syndrome in men. (HEPATOLOGY 2008.)
•Global digitalization and changing consumer behaviors drive unprecedented industry changes.•Investing in digital transformation remains a concern, with a high failure rate and lack of value ...creation.•Absence of a clear definition for digital transformation, the lack of a bridging taxonomy between industry and academia, and the necessity for a guiding model in digital transformation for organizations.•The study establish a digital transformation taxonomy by deconstructing the notion of digital transformation into various dimensions.•This study strives to investigate the prioritization of dimensions within the DT taxonomy.•Through empirical research, this study underscore essential aspects that firms should not overlook in their digital transformation initiatives.
Digital transformation (DT) is an adaptive strategy in the evolving tech and business landscape. It helps organizations enhance operations and customer experiences to remain competitive. However, defining digital transformation, creating a universal taxonomy, and developing a practical assessment model remain challenges. This study aims to establish a comprehensive DT taxonomy by deconstructing DT into various dimensions. The research goes a step further by developing sub-dimensions and indicators, offering essential tools for investigating an organization's DT status. The study emphasizes the importance of considering industry-specific approaches, with a focus on the retail sector as a practical case study. Our research employs a structured approach, including an extensive literature review, focus group interviews, and the utilization of the FAHP method and e-surveys to prioritize DT taxonomy dimensions. The study makes significant contributions, including providing a clear DT definition, bridging the gap between corporate and academic perspectives, and introducing a practical survey questionnaire for DT initiatives. We highlight the critical role of customer experience, DT training, and resource allocation, and introduce a conceptual model illustrating the dynamic relationship among organizational operations, DT technology, and process optimization. This model also proposed the moderating roles played by customer experience and resource allocation.
Infectious diseases are considered the greatest threat to the modern high-density shrimp aquaculture industry. Specificity, rapidity, and sensitivity of molecular diagnostic methods for the detection ...of asymptomatic infected shrimp allows preventive measures to be taken before disease outbreaks. Routine molecular detection of pathogens in infected shrimp can be made easier with the use of a direct polymerase chain reaction (PCR). In this study, four direct PCR reagent brands were tested, and results showed that the detection signal of direct PCR in hepatopancreatic tissue was more severely affected. In addition, portable capillary electrophoresis was applied to improve sensitivity and specificity, resulting in a pathogen detection limit of 25 copies/PCR-reaction. Juvenile shrimp from five different aquaculture ponds were tested for white spot syndrome virus infection, and the results were consistent with the Organization for Animal Health's certified standard method. Furthermore, this methodology could be used to examine single post larvae shrimp. The overall detection time was reduced by more than 58.2%. Therefore, the combination of direct PCR and capillary electrophoresis for on-site examination is valuable and has potential as a suitable tool for diagnostic, epidemiological, and pathological studies of shrimp aquaculture.
Food safety concerns regarding foodborne pathogen contamination have gained global attention due to its significant implications. In this study, we developed a detection system utilizing a PCR array ...combined with an automated magnetic bead-based system and CE technology to enable the detection of three foodborne pathogens, namely Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus. The results showed that our developed method could detect these pathogens at concentrations as low as 7.3 × 101, 6.7 × 102, and 6.9 × 102 cfu/mL, respectively, in the broth samples. In chicken samples, the limit of detection for these pathogens was 3.1 × 104, 3.5 × 103, and 3.9 × 102 cfu/g, respectively. The detection of these pathogens was accomplished without the necessity for sample enrichment, and the entire protocols, from sample preparation to amplicon analysis, were completed in approximately 3.5 h. Regarding the impact of the extraction method on detection capability, our study observed that an automated DNA extraction system based on the magnetic bead method demonstrated a 10-fold improvement or, at the very least, yielded similar results compared to the column-based method. These findings demonstrated that our developed model is effective in detecting low levels of these pathogens in the samples analyzed in this study. The PCR-CE method developed in this study may help monitor food safety in the future. It may also be extended to identify other foodborne pathogens across a wide range of food samples.
The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid ...(tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance.
Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αvβ3. We investigated the role of thyroid hormone‐induced internalization ...of nuclear integrin αv monomer. Physiological concentration of thyroxine (free T4, 10–10 M), but not 3,5,3'‐triiodo‐L‐thyronine (T3), induced cellular internalization and nuclear translocation of integrin αv monomer in human non‐small‐cell lung cancer (H522) and ovarian carcinoma (OVCAR‐3) cells. T4 did not complex with integrin αv monomer during its internalization. The αv monomer was phosphorylated by activated ERK1/2 when it heterodimerized with integrin β3 in vitro. Nuclear αv complexed with transcriptional coactivator proteins, p300 and STAT1, and with corepressor proteins, NCoR and SMRT. Nuclear αv monomer in T4‐exposed cells, but not integrin β3, bound to promoters of specific genes that have important roles in cancer cells, including estrogen receptor‐α, cyclooxygenase‐2, hypoxia‐inducible factor‐1α, and thyroid hormone receptor β1 in chromatin immunoprecipitation assay. In summary, monomeric αv is a novel coactivator regulated from the cell surface by thyroid hormone for the expression of genes involved in tumorigenesis and angiogenesis. This study also offers a mechanism for modulation of gene expression by thyroid hormone that is adjunctive to the nuclear hormone receptor (TR)‐T3 pathway.—Lin, H.‐Y., Su, Y.‐F., Hsieh, M.‐T., Lin, S., Meng, M., London, D., Lin, C., Tang, H.‐Y., Hwang, J., Davis, F. B., Mousa, S. A.and Davis, P. J., Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone. FASEB J. 27, 3209–3216 (2013). www.fasebj.org
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