Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. ...Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible due to unclear treatment durability, drug toxicity, logistical constraints related to directly observed treatment strategy (DOTS) and the lengthy treatment protocols. Together, these factors promote non-adherence, contributing to relapse and establishment of drug-resistant Mtb strains. Although antibiotic treatment of drug-susceptible Mtb is generally effective, drug-resistant TB has a treatment efficacy below 50% and can, in a proportion, develop into progressive, untreatable disease. Other immune compromising co-infections and/or co-morbidities require more complex prevention/treatment approaches, posing huge financial burdens to national health services. Novel TB treatment strategies, such as host-directed therapeutics, are required to complement pathogen-targeted approaches. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. This review discusses promising pre-clinical candidates and forerunning compounds at advanced stages of clinical investigation in TB host-directed therapeutic (HDT) efficacy trials. Such approaches are rationalized to improve outcome in TB and shorten treatment strategies.
Commercial photoplethysmography (PPG) sensors rely on the measurement of continuous-wave diffuse reflection signals (CW-DRS) to monitor heart rate. Using Monte Carlo modeling of light propagation in ...skin, we quantitatively evaluate the dependence of continuous-wave photoplethysmography (CW-PPG) in commercial wearables on source-detector distance (SDD). Specifically, when SDD increases from 0.5 mm to 3.3 mm, CW-PPG signal increases by roughly 846% for non-obese (NOB) skin and roughly 683% for morbidly obese (MOB) skin. Ultimately, we introduce the concept of time-of-flight PPG (TOF-PPG) which can significantly improve heart rate signals. Our model shows that the optimized TOF-PPG improves heart rate monitoring experiences by roughly 47.9% in NOB and 93.2% in MOB when SDD = 3.3 mm is at green light. Moving forward, these results will provide a valuable source for hypothesis generation in the scientific community to improve heart rate monitoring.
Neuropathic pain remains an area of considerable unmet clinical need. Research based on preclinical animal models has failed to deliver truly novel treatment options, questioning the predictive value ...of these models. This review addresses the shortcomings of rodent in vivo models commonly used in the field and highlights approaches which could increase their predictivity, including more clinically relevant assays, outcome measures and animal characteristics. The methodological quality of animal studies also needs to be improved. Low internal validity and incomplete reporting lead to a waste of valuable research resources and animal lives, and ultimately prevent an objective assessment of the true predictivity of in vivo models.
This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81 μeV. The search excludes the range of axion-photon couplings predicted by plausible ...models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses.
A Comprehensive Review on Eryptosis Pretorius, Etheresia; du Plooy, Jeanette N.; Bester, Janette
Cellular physiology and biochemistry,
11/2016, Letnik:
39, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, ...whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized and organized membrane structure, which interacts and reacts to inflammatory molecule insults, and undergo programmed cell death, similar to apoptosis, known as eryptosis. Over the past years, eryptosis studies have focussed on determining if membrane changes have occurred, particularly whether a phosphatidylserine (PS) flip, Ca2+ leakage into the cell, changes to ceramide and cell shrinkage have occurred. Mostly, flow cytometry is used, but confocal microscopy and ultrastructural studies also confirm eryptosis. Here, we provide a comprehensive overview of eryptosis, where we revisit the biochemical process of the process, review all literature in PUBMED, that is shown under the search word, “eryptosis”, and also discuss current methodologies to determine the presence of eryptosis; included in the discussion of the methodologies, we discuss a pitfalls section for each method. This paper is therefore a comprehensive synopsis of current knowledge of eryptosis and discusses how RBCs may provide an essential in vivo cell model system to study not only inflammation in disease, but also track disease progression and treatment regimes.
Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which can result in cardiac hypertrophy and subsequent heart failure, associated with pyroptosis, the ...pro-inflammatory programmed cell death. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d expression was substantially increased in streptozotocin (STZ)-induced diabetic rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, knockdown of mir-30d attenuated it. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic property of mir-30d, we found that forced expression of mir-30d upregulated caspase-1 and pro-inflammatory cytokines IL-1β and IL-18. Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These findings promoted us to propose a new signaling pathway leading to cardiomyocyte pyroptosis under hyperglycemic conditions: mir-30d↑→foxo3a↓→ ARC↓→caspase-1↑→IL-1β, IL-18↑→pyroptosis↑. Therefore, mir-30d may be a promising therapeutic target for the management of diabetic cardiomyopathy.
Non-rare-earth dual green and red-emitting Mn-doped ZnAl2O4 phosphors were successfully synthesized by a co-precipitation method. XRD and XPS spectra reveal that Mn ions in two valence states Mn2+ ...and Mn4+ are co-existed in the ZnAl2O4 host lattice. The ZnAl2O4:(Mn2+, Mn4+) phosphors exhibit two intense emission bands in the green and red spectral regions, peaking at 510 and 679 nm. It is demonstrated that the PL intensity ratio of green emission and red emission (IGreen/Ired) can simply be controlled by adjusting the annealing temperature and found to vary from 2.78 to 0.48 when increasing the temperature from 1200 to 1400 °C. A prototype red-emitting LED was fabricated using a 310-nm UV LED combined with the ZnAl2O4:0.5% (Mn2+, Mn4+) phosphor. The CIE color coordinates are x = 0.5643 and y = 0.2798, while the red-emitting LED is driven by 60 mA current. The quantum efficiency (QE) of the ZnAl2O4:0.5%Mn phosphor is estimated to be about 27.3%. To the best of our knowledge, this is the first time that the QE of Mn-doped ZnAl2O4 phosphor is reported.
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•Synthesizing dual green and red-emitting phosphors from non-rare-earth Mn-doped ZnAl2O4 materials.•Controlling the PL intensity ratio between green and red emission.•Fabricating a prototype of red-emitting LED with the CIE chromaticity coordinates of (0.5643; 0.2798).
Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply ...scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.
Abstract
Anti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the ...right combination is challenging and would benefit from high-content, high-throughput combinatorial screens directly on patient biopsies. However, such screens require a large amount of material, normally not available from patients. To address these challenges, we present a scalable microfluidic workflow, called Combi-Seq, to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout for drug effects. We devise a deterministic combinatorial DNA barcoding approach to encode treatment conditions, enabling the gene expression-based readout of drug effects in a highly multiplexed fashion. We apply Combi-Seq to screen the effect of 420 drug combinations on the transcriptome of K562 cells using only ~250 single cell droplets per condition, to successfully predict synergistic and antagonistic drug pairs, as well as their pathway activities.
The development of full-visible-spectrum phosphors is essential for next-generation light-emitting devices with better light quality. Herein, we report on a novel broad-band-emitting phosphor based ...on single-composition Al-doped ZnO phosphors. Under the UV excitation of 325 nm, the ZnO : Al phosphor exhibits a full spectrum emission in the visible wavelength range from 400 to 800 nm with a CIE chromaticity coordinate of (0.42, 0.48), a quantum efficiency of 43%, a color rendering index (CRI) of 74, a correlated color temperature (CCT) value of 3873 K and an activation energy of 0.22 eV. A prototype of a UV-pumped warm WLED with a high CRI of 87 and a CCT of 4067 K has been achieved by using only this broad-band-emitting Al3+-doped ZnO phosphor. The obtained results indicate that the single-composition Al3+-singly doped warm white emitting phosphor is a promising candidate for UV-pump warm white light-emitting diodes.
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