Outer membrane vesicles (OMVs) released from Gram-negative bacteria consist of lipids, proteins, lipopolysaccharides and other molecules. OMVs are associated with several biological functions such as ...horizontal gene transfer, intracellular and intercellular communication, transfer of contents to host cells, and eliciting an immune response in host cells. Although hypotheses have been made concerning the mechanism of biogenesis of these vesicles, research on OMV formation is far from complete. The roles of outer membrane components, bacterial quorum sensing molecules and some specific proteins in OMV biogenesis have been studied. This review discusses the different models that have been proposed for OMV biogenesis, along with details of the biological functions of OMVs and the likely scope of future research.
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•PDMS/CB nanocomposite has been successfully developed and tested as a photothermal actuator using an IR light source.•Critical Parameters, such as thermal and light absorbance, are ...thoroughly studied.•Maximum beam deflection of nanocomposite is found to be approximately 9 mm after illumination with IR light with strong repeatability.•The behaviour of the developed photothermal actuator is in line with the theoretical and experimental findings.
The new development of polymer-based actuators triggers the progress of nanocomposites. Polymer materials are currently used in sensors, microfluidic devices, electrical and thermal actuators, and energy harvesting applications due to ease of availability, excellent tolerable properties, and customizable properties. The polymer-based nanocomposite can be driven by various stimuli, which is the actuator's emerging field. Thus, photothermal actuation is a thurst area of research transforming light energy into mechanical energy through the polymer material. The photo-responsive material can be prepared and tested for photo-actuation by incorporating the nanoparticles into the polymer. The present work focuses on developing polydimethylsiloxane (PDMS) and carbon black (CB) nanocomposite. The objective here is to investigate the photothermal actuator's performance by illuminating the infrared (IR) light source and studying its most influential characteristics, such as absorbance, thermal conductivity, and the thermal expansion coefficient.
The PDMS / CB nanocomposite absorbs the IR light and then increases temperature, which is finally transformed into a beam deflection. Responses are measured as a result of time deflection using the Laser displacement sensor. It is noted that the deflection of the nanocomposite beam is linearly increased during illumination with light while it is exponentially decreasing when the light is turned off. The proposed polymer nanocomposite is approximately deflected by 9 mm in the duration of 16 s duration. Furthermore, the experimental deflection of the photothermal actuator is very close to theoretical results. The nanocomposite PDMS / CB reveals that there is an increase in absorbance by increasing the filler content. The nanocomposite conductivity is 35.2 % higher than the base material. As well, the thermal expansion coefficient decreases with an increase in carbon black content. The photothermal actuator's development is an ongoing process in which the material parameter, actuator geometry, and many more are modified. As a result, the photothermal bending performed can provide a means for various light-driven applications.
Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based ...computational method using a deep neural network architecture for DSS prediction.
The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS).
Area under the curve (AUC) in the YSM patients was 0.905 (
< 0.0001). AUC in the GHS patients was 0.880 (
< 0.0001). Using the cutoff selected in the YSM cohort, the computational model predicted DSS in the GHS cohort based on Kaplan-Meier (KM) analysis (
< 0.0001).
The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods.
•Mapping of ultrasonic bath for ultrasound assisted extraction of natural product.•Optimization of parameters for maximum extraction.•Position and shape of vessel has significant impact on extraction ...yield.•Mapping of ultrasonic bath can help to obtain maximum extraction yield.
The present work deals with the mapping of an ultrasonic bath for the maximum extraction of mangiferin from Mangifera indica leaves. I3− liberation experiments (chemical transformations) and extraction (physical transformations) were carried out at different locations in an ultrasonic bath and compared. The experimental findings indicated a similar trend in variation in an ultrasonic bath by both these methods. Various parameters such as position and depth of vessel in an ultrasonic bath, diameter and shape of a vessel, frequency and input power which affect the extraction yield have been studied in detail. Maximum yield of mangiferin obtained was approximately 31mg/g at optimized parameters: distance of 2.54cm above the bottom of the bath, 7cm diameter of vessel, flat bottom vessel, 6.35cm liquid height, 122W input power and 25kHz frequency. The present work indicates that the position and depth of vessel in an ultrasonic bath, diameter and shape of a vessel, frequency and input power have significant effect on the extraction yield. This work can be used as a base for all ultrasonic baths to obtain maximum efficiency for ultrasound assisted extraction.
Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has ...increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.
Titanium and titanium alloys exhibit a unique combination of strength and biocompatibility, which enables their use in medical applications and accounts for their extensive use as implant materials ...in the last 50 years. Currently, a large amount of research is being carried out in order to determine the optimal surface topography for use in bioapplications, and thus the emphasis is on nanotechnology for biomedical applications. It was recently shown that titanium implants with rough surface topography and free energy increase osteoblast adhesion, maturation and subsequent bone formation. Furthermore, the adhesion of different cell lines to the surface of titanium implants is influenced by the surface characteristics of titanium; namely topography, charge distribution and chemistry. The present review article focuses on the specific nanotopography of titanium, i.e. titanium dioxide (TiO2) nanotubes, using a simple electrochemical anodisation method of the metallic substrate and other processes such as the hydrothermal or sol-gel template. One key advantage of using TiO2 nanotubes in cell interactions is based on the fact that TiO2 nanotube morphology is correlated with cell adhesion, spreading, growth and differentiation of mesenchymal stem cells, which were shown to be maximally induced on smaller diameter nanotubes (15 nm), but hindered on larger diameter (100 nm) tubes, leading to cell death and apoptosis. Research has supported the significance of nanotopography (TiO2 nanotube diameter) in cell adhesion and cell growth, and suggests that the mechanics of focal adhesion formation are similar among different cell types. As such, the present review will focus on perhaps the most spectacular and surprising one-dimensional structures and their unique biomedical applications for increased osseointegration, protein interaction and antibacterial properties.
This unit presents the protocol for the NanoString nCounter Gene Expression Assay, a robust and highly reproducible method for detecting the expression of up to 800 genes in a single reaction with ...high sensitivity and linearity across a broad range of expression levels. The methodology serves to bridge the gap between genome-wide (microarrays) and targeted (real-time quantitative PCR) expression profiling. The nCounter assay is based on direct digital detection of mRNA molecules of interest using target-specific, color-coded probe pairs. It does not require the conversion of mRNA to cDNA by reverse transcription or the amplification of the resulting cDNA by PCR. Each target gene of interest is detected using a pair of reporter and capture probes carrying 35- to 50-base target-specific sequences. In addition, each reporter probe carries a unique color code at the 5' end that enables the molecular barcoding of the genes of interest, while the capture probes all carry a biotin label at the 3' end that provides a molecular handle for attachment of target genes to facilitate downstream digital detection. After solution-phase hybridization between target mRNA and reporter-capture probe pairs, excess probes are removed and the probe/target complexes are aligned and immobilized in the nCounter cartridge, which is then placed in a digital analyzer for image acquisition and data processing. Hundreds of thousands of color codes designating mRNA targets of interest are directly imaged on the surface of the cartridge. The expression level of a gene is measured by counting the number of times the color-coded barcode for that gene is detected, and the barcode counts are then tabulated.
Activation of cannabinoid CB1 receptors suppresses pathological pain but also produces unwanted central side effects. We hypothesized that a positive allosteric modulator of CB1 signaling would ...suppress inflammatory and neuropathic pain without producing cannabimimetic effects or physical dependence. We also asked whether a CB1 positive allosteric modulator would synergize with inhibitors of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist.
GAT211, a novel CB1 positive allosteric modulator, was evaluated for antinociceptive efficacy and tolerance in models of neuropathic and/or inflammatory pain. Cardinal signs of direct CB1-receptor activation were evaluated together with the propensity to induce reward or aversion and physical dependence. Comparisons were made with inhibitors of endocannabinoid deactivation (JZL184, URB597) or an orthosteric cannabinoid agonist (WIN55,212-2). All studies used 4 to 11 subjects per group.
GAT211 suppressed allodynia induced by complete Freund’s adjuvant and the chemotherapeutic agent paclitaxel in wild-type but not CB1 knockout mice. GAT211 did not impede paclitaxel-induced tumor cell line toxicity. GAT211 did not produce cardinal signs of direct CB1-receptor activation in the presence or absence of pathological pain. GAT211 produced synergistic antiallodynic effects with fatty acid amide hydrolase and monoacylglycerol lipase inhibitors in paclitaxel-treated mice. Therapeutic efficacy was preserved over 19 days of chronic dosing with GAT211, but it was not preserved with the monoacylglycerol lipase inhibitor JZL184. The CB1 antagonist rimonabant precipitated withdrawal in mice treated chronically with WIN55,212-2 but not in mice treated with GAT211. GAT211 did not induce conditioned place preference or aversion.
Positive allosteric modulation of CB1-receptor signaling shows promise as a safe and effective analgesic strategy that lacks tolerance, dependence, and abuse liability.
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