Nanoplasmonics is a rapidly growing field of research that opens up multiple opportunities toward practical applications. The understanding of the extreme confinement of light at the nanoscale has ...facilitated the development of a wide range of interesting materials for many different fields. Nanoparticles of noble metals, such as gold or silver, present unique optical properties that may end up making a large impact on our daily lives. Modern biomedical techniques can successfully treat cancer via plasmon‐mediated photothermal therapy, in which metal nanoprobes act as intense heaters to kill cancer cells. Moreover, our society is also seeing an increasing interest in the development of alternative (green) energy sources, where plasmonic nanostructures are also considered to provide an advantage, e.g., improving the performance and feasibility of photovoltaic devices. In this progress report, relevant advances and applications of plasmonic nanoparticles, from energy to health, are discussed, and their potential implications in future society are highlighted.
Plasmonic nanoparticles present unique optical properties that render them extremely useful for application in many different fields. Current applications of plasmonic nanoparticles include their use as nanoheaters to effectively kill cancer cells, but they also contribute to the progress of solar energy technology. In this progress report, modern applications of plasmonic nanoparticles from which society may ultimately benefit are highlighted.
Abstract
Patients undergoing cardiac surgery represent a challenge in terms of pain management due to multiple factors relating to the patients and to the procedure itself. Our aim was to identify ...the influence of levels of preoperative anxiety on postoperative pain in patients undergoing cardiac surgery and explore associations between preoperative anxiety, postoperative pain, analgesic requirements, and sex. We present a prospective cohort study of 116 patients undergoing cardiac surgery between January and April 2020. Preoperative anxiety was evaluated using the State-Trait Anxiety Inventory and the amount of morphine needed to keep pain intensity below 4 on the verbal numerical rating scale was recorded for 48 h post-surgery. Given the extracorporeal circulation time, type of surgery and body surface, it was observed that every percentile increase in preoperative state anxiety led to an extra 0.068 mg of morphine being administered. For each extra year of age, the amount of morphine needed decreased by 0.26 mg, no difference was observed between men and women in terms of preoperative anxiety or postoperative analgesics requirements. It may be concluded that in cardiac surgery, postoperative analgesic requirements increased with higher levels of preoperative state anxiety and decreased for every extra year of age.
Care staff in nursing homes work in a challenging environment, and the COVID‐19 pandemic has exacerbated those challenges in an unprecedented way. On the other hand, the sense of coherence (SOC) is a ...competence that could help these professionals perceive the situation as understandable, manageable and meaningful. This study aims to analyse the extent to which potential risk and protective factors against burnout have affected nursing home workers during the COVID‐19 pandemic and to assess the contribution of these factors to their burnout. Three hundred forty professionals who worked in nursing homes in Spain completed a survey and reported on their sociodemographic characteristics and their organisational characteristics of the job related to COVID‐19, SOC and burnout. Multiple linear regression analyses were performed. The results showed that the SOC is highly related to the dimensions of burnout and is a protective factor against this. In addition, the increase in hours has a negative effect, facilitating inadequate responses to stressful situations; and whereas perceived social support and availability of resources have a protective effect, the deterioration in mental and physical health is the most important risk factor. This study could help better understand the psychological consequences of the effort that nursing home workers and can also help design mental health prevention and care interventions for workers that provide them with resources and supports that foster their coping skills.
West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus, which main natural hosts are birds but it also infects equines and humans, among other mammals. As in the case of other ...plus-stranded RNA viruses, WNV replication is associated to intracellular membrane rearrangements. Based on results obtained with a variety of viruses, different cellular processes have been shown to play important roles on these membrane rearrangements for efficient viral replication. As these processes are related to lipid metabolism, fatty acid synthesis, as well as generation of a specific lipid microenvironment enriched in phosphatidylinositol-4-phosphate (PI4P), has been associated to it in other viral models. In this study, intracellular membrane rearrangements following infection with a highly neurovirulent strain of WNV were addressed by means of electron and confocal microscopy. Infection of WNV, and specifically viral RNA replication, were dependent on fatty acid synthesis, as revealed by the inhibitory effect of cerulenin and C75, two pharmacological inhibitors of fatty acid synthase, a key enzyme of this process. However, WNV infection did not induce redistribution of PI4P lipids, and PI4P did not localize at viral replication complex. Even more, WNV multiplication was not inhibited by the use of the phosphatidylinositol-4-kinase inhibitor PIK93, while infection by the enterovirus Coxsackievirus B5 was reduced. Similar features were found when infection by other flavivirus, the Usutu virus (USUV), was analyzed. These features of WNV replication could help to design specific antiviral approaches against WNV and other related flaviviruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that affects humans and can cause severe neurological complications, including Guillain-Barré syndrome and microcephaly. Since 2007 there ...have been three large outbreaks; the last and larger spread in the Americas in 2015. Actually, ZIKV is circulating in the Americas, Southeast Asia, and the Pacific Islands, and represents a potential pandemic threat. Given the rapid ZIKV dissemination and the severe neurological and teratogenic sequelae associated with ZIKV infection, the development of a safe and efficacious vaccine is critical. In this study, we have developed and characterized the immunogenicity and efficacy of a novel ZIKV vaccine based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the ZIKV prM and E structural genes (termed MVA-ZIKV). MVA-ZIKV expressed efficiently the ZIKV structural proteins, assembled in virus-like particles (VLPs) and was genetically stable upon nine passages in cell culture. Immunization of mice with MVA-ZIKV elicited antibodies that were able to neutralize ZIKV and induced potent and polyfunctional ZIKV-specific CD8
T cell responses that were mainly of an effector memory phenotype. Moreover, a single dose of MVA-ZIKV reduced significantly the viremia in susceptible immunocompromised mice challenged with live ZIKV. These findings support the use of MVA-ZIKV as a potential vaccine against ZIKV.
Abstract
Background
Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on ...bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide.
Results
A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients. Real-time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptomics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregulation of hexokinases 2 and 3 (
Hk2
and
Hk3
) and pyruvate dehydrogenase kinase 4 (
Pdk4
). Treatment of infected mice with the Hk inhibitor, 2-deoxy-D-glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV-induced neuroinflammation.
Conclusions
These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology.
Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a ...great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.
Accurate 3D nanometrology of catalysts with small nanometer-sized particles of light 3d or 4d metals supported on high-atomic-number oxides is crucial for understanding their functionality. However, ...performing quantitative 3D electron tomography analysis on systems involving metals like Pd, Ru, or Rh supported on heavy oxides (e.g., CeO2) poses significant challenges. The low atomic number (Z) of the metal complicates discrimination, especially for very small nanoparticles (1–3 nm). Conventional reconstruction methods successful for catalysts with 5d metals (e.g., Au, Pt, or Ir) fail to detect 4d metal particles in electron tomography reconstructions, as their contrasts cannot be effectively separated from those of the underlying support crystallites. To address this complex 3D characterization challenge, we have developed a full deep learning (DL) pipeline that combines multiple neural networks, each one optimized for a specific image-processing task. In particular, single-image super-resolution (SR) techniques are used to intelligently denoise and enhance the quality of the tomographic tilt series. U-net generative adversarial network algorithms are employed for image restoration and correcting alignment-related artifacts in the tilt series. Finally, semantic segmentation, utilizing a U-net-based convolutional neural network, splits the 3D volumes into their components (metal and support). This approach enables the visualization of subnanometer-sized 4d metal particles and allows for the quantitative extraction of catalytically relevant structural information, such as particle size, sphericity, and truncation, from compressed sensing electron tomography volume reconstructions. We demonstrate the potential of this approach by characterizing nanoparticles of a metal widely used in catalysis, Pd (Z = 46), supported on CeO2, a very high density (7.22 g/cm3) oxide involving a quite high-atomic-number element, Ce (Z = 58).
Mosquito-borne flaviviruses are a group of RNA viruses that constitute global threats for human and animal health. Replication of these pathogens is strictly dependent on cellular lipid metabolism. ...We have evaluated the effect of the pharmacological activation of AMP-activated protein kinase (AMPK), a master regulator of lipid metabolism, on the infection of three medically relevant flaviviruses, namely, West Nile virus (WNV), Zika virus (ZIKV), and dengue virus (DENV). WNV is responsible for recurrent outbreaks of meningitis and encephalitis, affecting humans and horses worldwide. ZIKV has caused a recent pandemic associated with birth defects (microcephaly), reproductive disorders, and severe neurological complications (Guillain-Barré syndrome). DENV is the etiological agent of the most prevalent mosquito-borne viral disease, which can induce a potentially lethal complication called severe dengue. Our results showed, for the first time, that activation of AMPK using the specific small molecule activator PF-06409577 reduced WNV, ZIKV, and DENV infection. This antiviral effect was associated with an impairment of viral replication due to the modulation of host cell lipid metabolism exerted by the compound. These results support that the pharmacological activation of AMPK, which currently constitutes an important pharmacological target for human diseases, could also provide a feasible approach for broad-spectrum host-directed antiviral discovery.
To enlarge the applications of whole wheat grain (WWG) and wheat bran (WB) as functional ingredients in foodstuffs that can promote human health, researchers have explored bioprocessing approaches to ...improve the bioaccessibility of phenolic compounds from these food matrices and, subsequently, their biological effects. The objective of this study was to compare the composition in nutrients, anti-nutrients, and bioactive compounds of WWG and WB, and their respective bioprocessed products: sprouted wheat (GERM) and WB hydrolysate (stabilized by spray-drying SPD and microencapsulated MEC). In addition, to evaluate the functional properties of these ingredients, the bioaccessibility of phenolic compounds and their potential antioxidant and anti-inflammatory activities were monitored in different digestion steps. GERM had increased amounts of insoluble dietary fiber, higher diversity of oligosaccharides, and higher concentration of monosaccharides, free phosphorous, and phenolic compounds than WWG. SPD had improved content of soluble dietary fiber, oligosaccharides, monosaccharides, free phosphorous, and phenolic compounds (vs. WB), whereas MEC was mainly composed of protein and had nearly 2-fold lower content of SPD components. All the ingredients showed lower amounts of phytic acid as compared with raw materials. In all samples, hydroxycinnamic acids were the most representative polyphenols followed by minor amounts of hydroxybenzoic acids and flavonoids. Gastrointestinal digestion of GERM, SPD, and MEC revealed high stability of total phenolic compounds in both gastric and intestinal phases. Hydroxycinnamic acids were the most bioaccessible compounds during digestion among the three bioprocessed wheat ingredients studied, although their bioaccessibility varied across ingredients. In this sense, the bioaccessibility of ferulic acid (FA) derivatives increased in GERM with progression of the digestion, while it was reduced in SPD and MEC up to the end of the intestinal phase. Microencapsulation of SPD with pea protein led to generally to lower bioaccessible amounts of phenolic acids. Comparison analysis of biological effects highlighted SPD for its most potent antioxidant effects in the gastrointestinal tract (3 out 4 antioxidant parameters with highest values), while no clear differences were observed with regard to
anti-inflammatory activity. Overall, these results support the potential application of GERM, SPD, and MEC as functional and nutraceutical ingredients.