Albumins, in the form of nanoparticles, are increasingly used as drug carriers in the medical field, and the size effect of these nanomaterials is of major importance since it may affect their ...bioavailability and the in vivo behaviour after intravenous injection. This research provides a comprehensive study on the preparation of BSA nanoparticles, based on a simple coacervation method, with suitable size, size distribution, and surface charge for drug-delivery applications. Numerous experimental variables were examined in order to characterize their impact on nanoparticle size, distribution, electrophoretic mobility, and yield. Particle size was controlled by adjusting self-assembly phenomena of the protein molecules, which was affected by preparation conditions including BSA content, pH, and ionic strength (a parameter that strongly influences nanoparticle formation but surprisingly has not been previously studied in detail). Small particles with a narrow size distribution were obtained under experimental conditions where the repulsion between BSA molecules was high, i.e. at pH values far from the isoelectric point of the protein and low salt concentration. Changes in temperature, volume, and rate of addition of the dehydrating agent (ethanol) also affect nanoparticle characteristics, as they influence the nucleation rate and particle growth. The effect of these experimental conditions on the quantity of protein still dissolved in the aqueous phase after desolvation (i.e. the yield of BSA nanoparticles) was also studied. Nanoparticles surface charge was modulated with the extension of cross-linking. Finally, long-term colloidal stability of samples was evaluated after 2 months of storage.
A nanocomposite is fabricated by formation of a conductive polymer, using in situ oxidative polymerization, inside a thermosensitive crosslinked hydrogel. FE-SEM micrographs show the nanometric ...domains of the conductive material (polyaniline, PANI) dispersed in the hydrogel matrix based on cross linked poly(N-isopropylacrylamide) (PNIPAm). The thermosensitive properties of PNIPAm and copolymers with 2-acrylamido-2-methyl propane sulfonic acid (AMPS) are not affected by the presence of conductive polymer nanoparticles. The incorporation of PANI improves the mechanical properties of the hydrogel allowing it to swell up to 30,000% without breaking. Since the conductive polymer absorbs strongly microwave radiation at pH<4 and heats up, the nanocomposite containing PANI suffer phase transition upon microwave irradiation. At pH>4, PANI is not conductive and the nanocomposite becomes insensitive to microwaves. However, using a pH insensitive conductive polymer (polypyrrole, PPy) in the nanocomposite makes it sensitive to microwaves at all pH values. The nanocomposite is used in a chemomechanical actuator where drug release is driven remotely by microwave irradiation. Since the PNIPAm-co-2%AMPS/PANI nanocomposite is soft and electronically conductive, could be used as pressure/force sensor. It is shown that a compressive force applied on a cylinder of that nanocomposite increases the conductivity of material. Additionally a switch is built which turns off upon microwave irradiation. Therefore, the nanocomposites are potential candidates for different technological applications, such as: a force/pressure electrical sensor, a drug delivery device driven remotely by microwaves, pH or temperature electrical switches and an electric switch driven by microwaves.
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is ...accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA
) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8
T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8
T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA
cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8
T-lymphocyte activation as a tumour-promoting mechanism.
This study analyzes the feasibility of using biomass combustion ash waste (rice husk or wood ash from boards) as secondary raw materials in the manufacture of clay bricks.
The ash was characterized ...using particle size distribution analysis, chemical composition analysis by X-ray diffraction (XRD) and X-ray fluorescence (XRF), thermal analysis, elemental analysis, and scanning electron microscopy (SEM). Either rice husk ash or wood ash was used to replace different amounts (10–30wt%) of clay in brick manufacture. Brick samples were formed by compression at 54.5MPa and fired at temperatures of 900 or 1000°C for 4h, at a heating rate of 3°C/min. The bricks’ properties were compared to conventional products containing only clay and prepared following standard procedures. The bricks’ technological properties depended on type and amount of ash used, and firing temperature. The results showed small variations due to firing temperature. Firing at 1000°C achieved greater densification and thus lower water absorption and higher compressive strength firing at 900°C produced higher porosity, which reduced compressive strength. Based on the results, 1000°C was selected as the optimal firing temperature; and 10wt% rice husk ash and 20wt% wood ash as the optima amounts of biomass ash waste. Moreover, the bricks containing wood ash showed properties similar to the control bricks containing only clay and improved thermal conductivity. Finally, the bricks containing 10wt% rice husk ash and 30wt% wood ash fulfilled standard requirements for clay masonry units.
This paper investigates the incentives and inhibiting factors of eco-innovation capacities in the firm. Firms materialize the objectives of eco-innovation from a reactive attitude to external ...pressures, to a more proactive attitude that implies the voluntary incorporation of eco-innovation activities. This variability in the behaviour of companies with respect to the level of eco-innovation development has been a motivator for the research. However, despite the importance of this research question, this has been approached in a dispersed way from multiple approaches. From a dynamic capabilities perspective, we assume that the innovation capacity of the firm encourages eco-innovations. Our paper is focused on the process of eco-innovation, identifying the elements that facilitate or hinder the eco-innovation in the firm. We study the Spanish case, using a panel from the Spanish Innovation Survey, with a sample of 5461 Spanish firms. The results highlight that the complexity of the eco-innovation process negatively affects the decision to develop eco-innovations. However, our results suggest that institutions and organizations of the Spanish environment are making efforts to compensate these obstacles and provide incentives to develop eco-innovations.
•We model investigates the incentives and inhibiting factors of eco-innovation.•Our focus is on the process of eco-innovation from dynamic capabilities perspective.•The complexity of the eco-innovation process negatively affects to develop eco-innovations.•Results show that the experience facilitates the development of future eco-innovations.•The institutions provide incentives to develop eco-innovations.
Phenotypic plasticity has been suggested as the main mechanism for species persistence under a global change scenario, and also as one of the main mechanisms that alien species use to tolerate and ...invade broad geographic areas. However, contrasting with this central role of phenotypic plasticity, standard models aimed to predict the effect of climatic change on species distributions do not allow for the inclusion of differences in plastic responses among populations. In this context, the climatic variability hypothesis (CVH), which states that higher thermal variability at higher latitudes should determine an increase in phenotypic plasticity with latitude, could be considered a timely and promising hypothesis. Accordingly, in this study we evaluated, for the first time in a plant species (Taraxacum officinale), the prediction of the CVH. Specifically, we measured plastic responses at different environmental temperatures (5 and 20°C), in several ecophysiological and fitness-related traits for five populations distributed along a broad latitudinal gradient. Overall, phenotypic plasticity increased with latitude for all six traits analyzed, and mean trait values increased with latitude at both experimental temperatures, the change was noticeably greater at 20° than at 5°C. Our results suggest that the positive relationship found between phenotypic plasticity and geographic latitude could have very deep implications on future species persistence and invasion processes under a scenario of climate change.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of temperature cycle on the void volume fraction, shape and spatial distribution was determined by means of X-ray microtomography in 0
10 AS4/8552 composite laminates manufactured by ...compression molding. Cure temperatures were designed to obtain different processing windows while the overall degree of cure was equivalent, leading to laminates with average porosities in the range 0.4% and 2.9%. Regardless of the final porosity, voids were elongated, oriented parallel to the fibers and concentrated in channels along the width of the laminate as a result of the inhomogeneous process of consolidation and resin flow along the fibers. The interlaminar shear strength was found to be controlled by the void volume fraction in panels with porosity above 1%.
A CRISPR-Cas Cure for HIV/AIDS Hussein, Mouraya; Molina, Mariano A; Berkhout, Ben ...
International journal of molecular sciences,
01/2023, Letnik:
24, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Human immunodeficiency virus (HIV) infections and HIV-induced acquired immunodeficiency syndrome (AIDS) continue to represent a global health burden. There is currently no effective vaccine, nor any ...cure, for HIV infections; existing antiretroviral therapy can suppress viral replication, but only as long as antiviral drugs are taken. HIV infects cells of the host immune system, and it can establish a long-lived viral reservoir, which can be targeted and edited through gene therapy. Gene editing platforms based on the clustered regularly interspaced palindromic repeat-Cas system (CRISPR-Cas) have been recognized as promising tools in the development of gene therapies for HIV infections. In this review, we evaluate the current landscape of CRISPR-Cas-based therapies against HIV, with an emphasis on the infection biology of the virus as well as the activity of host restriction factors. We discuss the potential of a combined CRISPR-Cas approach that targets host and viral genes to activate antiviral host factors and inhibit viral replication simultaneously. Lastly, we focus on the challenges and potential solutions of CRISPR-Cas gene editing approaches in achieving an HIV cure.
The aim of this study was to evaluate the transfer of the most widely used antibiotics in dairy goats from milk to cheese as well as their effect on the cheese-making process and cheese ...characteristics during ripening. Antibiotic-free milk was spiked individually with 7 veterinary drugs (amoxicillin, benzylpenicillin, cloxacillin, erythromycin, ciprofloxacin, enrofloxacin, and oxytetracycline) at an equivalent concentration of the European Union maximum residue limit. Spiked goat milk was used to make mature Tronchón cheeses, which were analyzed at 0, 30, and 60 d of maturation to determine pH, chemical composition, proteolytic and lipolytic activities, and color and textural properties. A sensory evaluation of 60-d ripened cheeses was carried out. Cheeses from raw antibiotic-free goat milk were made simultaneously to be used as reference. The cheese-making process was unaffected by the presence of most antibiotics evaluated. Only erythromycin and oxytetracycline significantly increased the time required for cheese production (122 ± 29 and 108 ± 25 min, respectively). However, variable amounts of antibiotics, ranging from 7.4 to 68%, were transferred from milk to cheese, with oxytetracycline and quinolones showing the highest retention rates. In general, antibiotic residues present in the cheeses at the beginning of maturation decrease significantly along time. Thus, β-lactams and erythromycin residues were not detectable after 30 d of ripening. However, relatively high concentrations of enrofloxacin (148 ± 12 µg/kg) and ciprofloxacin (253 ± 24 µg/kg) residues were found in the cheeses after 60 d of maturation. The quality characteristics of the Tronchón cheeses were only slightly affected by such substances, with few significant differences in the free fatty acid concentration and color and textural properties of the cheeses. Results herein indicate that the use of goat milk containing antibiotics, such as quinolones, at the European Union maximum residue limit for cheese production could adversely affect the safety of the final products because relatively high concentrations of these substances could be retained in soft and semi-mature cheeses, making it necessary to assess the risk for consumer health. Studies on the partition of the antibiotic substances during cheese-making, using specific technologies, would be convenient to guarantee the safety of cheese and related products.
Background and purpose
An association between high blood pressure (BP) in acute intracerebral hemorrhage (ICH) and hematoma growth (HG) has not been clearly demonstrated. Therefore, the impact of BP ...changes and course on HG and clinical outcome in patients with acute ICH was determined.
Methods
In total, 117 consecutive patients with acute (<6 h) supratentorial ICH underwent baseline and 24‐h CT scans, CT angiography for the detection of the spot sign and non‐invasive BP monitoring at 15‐min intervals over the first 24 h. Maximum and minimum BP, maximum BP increase and drop from baseline, and BP variability values from systolic BP (SBP), diastolic BP and mean arterial pressure (MAP) were calculated. SBP and MAP loads were defined as the proportion of readings >180 and >130 mmHg, respectively. HG (>33% or >6 ml), early neurological deterioration (END) and 3‐month mortality were recorded.
Results
Baseline BP variables were unrelated to either HG or clinical outcome. Conversely, SBP 180‐load independently predicted HG (odds ratio 1.05, 95% CI 1.010–1.097, P = 0.016), whilst both SBP 180‐load (odds ratio 1.04, 95% CI 1.001–1.076, P = 0.042) and SBP variability (odds ratio 1.2, 95% CI 1.047–1.380, P = 0.009) independently predicted END. Although none of the BP monitoring variables was associated with HG in the spot‐sign‐positive group, higher maximum BP increases from baseline and higher SBP and MAP loads were significantly related to HG in the spot‐sign‐negative group.
Conclusions
In patients with acute supratentorial ICH, SBP 180‐load independently predicts HG, whilst both SBP 180‐load and SBP variability predict END.
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