18 research outputs found

    Outlook for inverse design in nanophotonics

    Full text link
    Recent advancements in computational inverse design have begun to reshape the landscape of structures and techniques available to nanophotonics. Here, we outline a cross section of key developments at the intersection of these two fields: moving from a recap of foundational results to motivation of emerging applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure

    Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase.

    Get PDF
    Metformin is a first-line drug for the treatment of individuals with type 2 diabetes, yet its precise mechanism of action remains unclear. Metformin exerts its antihyperglycemic action primarily through lowering hepatic glucose production (HGP). This suppression is thought to be mediated through inhibition of mitochondrial respiratory complex I, and thus elevation of 5'-adenosine monophosphate (AMP) levels and the activation of AMP-activated protein kinase (AMPK), though this proposition has been challenged given results in mice lacking hepatic AMPK. Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin. We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment. We observe this during a metformin tolerance test and in a metformin-euglycemic clamp that we have developed. The antihyperglycemic effect of metformin in high-fat diet-fed diabetic FBP1-KI mice was also significantly blunted compared to wild-type controls. Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects

    Interaction of Copper-Based Nanoparticles to Soil, Terrestrial, and Aquatic Systems: Critical Review of the State of the Science and Future Perspectives

    Get PDF
    In the past two decades, increased production and usage of metallic nanoparticles (NPs) has inevitably increased their discharge into the different compartments of the environment, which ultimately paved the way for their uptake and accumulation in various trophic levels of the food chain. Due to these issues, several questions have been raised on the usage of NPs in everyday life and has become a matter of public health concern. Among the metallic NPs, Cu-based NPs have gained popularity due to their cost-effectiveness and multifarious promising uses. Several studies in the past represented the phytotoxicity of Cu-based NPs on plants. However, comprehensive knowledge is still lacking. Additionally, the impact of Cu-based NPs on soil organisms such as agriculturally important microbes, fungi, mycorrhiza, nematode, and earthworms are poorly studied. This review article critically analyses the literature data to achieve a more comprehensive knowledge on the toxicological profile of Cu-based NPs and increase our understanding of the effects of Cu-based NPs on aquatic and terrestrial plants as well as on soil microbial communities. The underlying mechanism of biotransformation of Cu-based NPs and the process of their penetration into plants has also been discussed herein. Overall, this review could provide valuable information to design rules and regulations for the safe disposal of Cu-based NPs into a sustainable environment

    Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes : a systematic review

    No full text
    The management of diabetic foot ulcers (DFU) remains a challenge, and there is continuing uncertainty concerning optimal approaches to wound healing. The International Working Group of the Diabetic Foot (IWGDF) working group on wound healing has previously published systematic reviews of the evidence in 2008, 2012 and 2016 to inform protocols for routine care and to highlight areas which should be considered for further study. The working group has now updated this review by considering papers on the interventions to improve the healing of DFU's published between June 2014 and August 2018. Methodological quality of selected studies was independently assessed by a minimum of two reviewers using the recently published 21-point questionnaire as recommended by IWGDF/European Wound Management Association, as well as the previously incorporated Scottish Intercollegiate Guidelines Network criteria. Of the 2275 papers identified, 97 were finally selected for grading following full text review. Overall, there has been an improvement in study design and a significant rise in the number of published studies. While previous systematic reviews did not find any evidence to justify the use of newer therapies, except for negative pressure wound therapy in post-surgical wounds, in this review we found additional evidence to support some interventions including a sucrose-octasulfate dressing, the combined leucocyte, fibrin and platelet patch as well as topical application of some placental membrane products, all when used in addition to usual best care. Nonetheless, the assessment and comparison of published trials remains difficult with marked clinical heterogeneity between studies: in patient selection, study duration, standard of usual care provision and the timing and description of the clinical endpoints
    corecore