Display omitted
Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, the development of innovative therapeutic ...strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged as promising tools for addressing CVDs. However, inherent challenges associated with RNA, such as poor cellular uptake, susceptibility to RNase degradation, and capture by the reticuloendothelial system, underscore the necessity of combining these therapies with effective drug delivery systems.
Various non-viral delivery systems, including extracellular vesicles, lipid-based carriers, polymeric and inorganic nanoparticles, as well as hydrogels, have shown promise in enhancing the efficacy of RNA therapeutics. In this review, we offer an overview of the most relevant RNA-based therapeutic strategies explored for addressing CVDs and emphasize the pivotal role of delivery systems in augmenting their effectiveness. Additionally, we discuss the current status of these therapies and the challenges that hinder their clinical translation.
Malignant melanoma is the most aggressive form of skin cancer and accounts for about 3% of all cases of malignant tumour. Its incidence is increasing worldwide and it is becoming resistant to current ...therapeutic agents. Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. This paper systematically and critically surveys all natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and maps the mechanisms of action for these underexploited properties. As a result, over 30 natural active principles are described acting mainly through their antagonistic effects upon the TNF-α and EP2 receptors or the suppression of several protein kinases involved in metastatic pathways such as RAS, PI3K, ERK and FAK. Also, some were able to reduce the level of mesenchymal biomarkers such as N-cadherin and/or elevate the expression of other molecules such as E-cadherin. Consequently, downstream transcription factors namely NF-kB, AP-1, ATF-2, CREB, and HIF were inactivated leading to diminished production of MMPs, IL-1, IL-6, COX-2, VEGF and GM-CSF. This review also discusses the opportunity of combination therapies based on natural products and approved drugs, such as the combination of EGCG and dacarbazine, or the combination of two natural compounds such as quercetin and sulforaphane.
Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were originally commissioned by the ...Department of Health and developed during 1998–2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were first published in January 2001 and updated in 2007. A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective for the prevention of HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. The Department of Health commissioned a review of new evidence and we have updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the epic2 guidelines published in 2007 remain robust, relevant and appropriate, but some guideline recommendations required adjustments to enhance clarity and a number of new recommendations were required. These have been clearly identified in the text. In addition, the synopses of evidence underpinning the guideline recommendations have been updated. These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence. National evidence-based guidelines are broad principles of best practice that need to be integrated into local practice guidelines and audited to reduce variation in practice and maintain patient safety. Clinically effective infection prevention and control practice is an essential feature of patient protection. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of health care in NHS hospitals in England can be minimised.
In recent years, spin-orbit effects have been widely used to produce and detect spin currents in spintronic devices. The peculiar symmetry of the spin Hall effect allows creation of a spin ...accumulation at the interface between a metal with strong spin-orbit interaction and a magnetic insulator, which can lead to a net pure spin current flowing from the metal into the insulator. This spin current applies a torque on the magnetization, which can eventually be driven into steady motion. Tailoring this experiment on extended films has proven to be elusive, probably due to mode competition. This requires the reduction of both the thickness and lateral size to reach full damping compensation. Here we show clear evidence of coherent spin-orbit torque-induced auto-oscillation in micron-sized yttrium iron garnet discs of thickness 20 nm. Our results emphasize the key role of quasi-degenerate spin-wave modes, which increase the threshold current.
ASASSN-14ae: a tidal disruption event at 200 Mpc Holoien, T. W.-S; Prieto, J. L; Bersier, D ...
Monthly notices of the Royal Astronomical Society,
12/2014, Letnik:
445, Številka:
3
Journal Article
Recenzirano
Odprti dostop
ASASSN-14ae is a candidate tidal disruption event (TDE) found at the centre of SDSS J110840.11+340552.2 (d ≃ 200 Mpc) by the All-Sky Automated Survey for Supernovae (ASAS-SN). We present ground-based ...and Swift follow-up photometric and spectroscopic observations of the source, finding that the transient had a peak luminosity of L ≃ 8 × 1043 erg s−1 and a total integrated energy of E ≃ 1.7 × 1050 erg radiated over the ∼5 months of observations presented. The blackbody temperature of the transient remains roughly constant at T ∼ 20 000 K while the luminosity declines by nearly 1.5 orders of magnitude during this time, a drop that is most consistent with an exponential, L ∝ e-t/t
0
with t
0 ≃ 39 d. The source has broad Balmer lines in emission at all epochs as well as a broad He ii feature emerging in later epochs. We compare the colour and spectral evolution to both supernovae and normal AGN to show that ASASSN-14ae does not resemble either type of object and conclude that a TDE is the most likely explanation for our observations. At z = 0.0436, ASASSN-14ae is the lowest-redshift TDE candidate discovered at optical/UV wavelengths to date, and we estimate that ASAS-SN may discover 0.1–3 of these events every year in the future.
We present ground-based and Swift photometric and spectroscopic observations of the candidate tidal disruption event (TDE) ASASSN-14li, found at the centre of PGC 043234 (d ... 90 Mpc) by the All-Sky ...Automated Survey for SuperNovae (ASAS-SN). The source had a peak bolometric luminosity of ... and a total integrated energy of ... erg radiated over the ~6 months of observations presented. The UV/optical emission of the source is well fitted by a blackbody with roughly constant temperature of T ... 35,000 K, while the luminosity declines by roughly a factor of 16 over this time. The optical/UV luminosity decline is broadly consistent with an exponential decline, ..., with t0 ... 60 d. ASASSN-14li also exhibits soft X-ray emission comparable in luminosity to the optical and UV emission but declining at a slower rate, and the X-ray emission now dominates. Spectra of the source show broad Balmer and helium lines in emission as well as strong blue continuum emission at all epochs. We use the discoveries of ASASSN-14li and ASASSN-14ae to estimate the TDE rate implied by ASAS-SN, finding an average rate of ... per galaxy with a 90 per cent confidence interval of ... per galaxy. ASAS-SN found roughly 1 TDE for every 70 Type Ia supernovae in 2014, a rate that is much higher than that of other surveys. (ProQuest: ... denotes formulae/symbols omitted.)
Magnetoelectric coupling between magnetic and electrical properties presents valuable degrees of freedom for applications. The two most promising scenarios are magnetic-field sensors that could ...replace low-temperature superconducting quantum interference devices, and electric-write magnetic-read memory devices that combine the best of ferroelectric and magnetic random-access memory. The former scenario requires magnetically induced continuous and reversible changes in electrical polarization. These are commonly observed, but the coupling constants thus obtained are invalid for data-storage applications, where the more difficult to achieve and rarely studied magnetic response to an electric field is required. Here, we demonstrate electrically induced giant, sharp and persistent magnetic changes (up to 2.3×10−7 s m−1) at a single epitaxial interface in ferromagnetic 40 nm La0.67Sr0.33MnO3 films on 0.5 mm ferroelectric BaTiO3 substrates. X-ray diffraction confirms strain coupling via ferroelastic non-180 BaTiO3 domains. Our findings are valid over a wide range of temperatures including room temperature, and should inspire further study with single epitaxial interfaces.
We present ~47,000 periodic variables found during the analysis of 5.4 million variable star candidates within a 20,000 degsup 2 region covered by the Catalina Surveys Data Release-1 (CSDR1). ...Combining these variables with type ab RR Lyrae from our previous work, we produce an online catalog containing periods, amplitudes, and classifications for ~61,000 periodic variables. By cross-matching these variables with those from prior surveys, we find that >90% of the ~8000 known periodic variables in the survey region are recovered. Based on the examination of 31,000 contact binary light curves we find evidence for two subgroups exhibiting irregular light curves. One subgroup presents significant variations in mean brightness that are likely due to chromospheric activity. The other subgroup shows stable modulations over more than a thousand days and thereby provides evidence that the O'Connell effect is not due to stellar spots.
PDF
