Search

Purpose Reduced exposure to echinocandins has been reported in specific patient populations, such as critically ill patients; however, fixed dosing strategies are still employed. The present review examines the accumulated evidence supporting echinocandin therapeutic drug monitoring (TDM) and summarizes available assays and sampling strategies. Methods A literature search was conducted using PubMed® in December 2020, with search terms such as echinocandins, anidulafungin, caspofungin, micafungin, or rezafungin with pharmacology, pharmacokinetics, pharmacodynamics, drug-drug interactions, therapeutic drug monitoring, resistance, drug susceptibility testing, toxicity, adverse drug reactions, bioanalysis, chromatography, and mass spectrometry. Data on pharmacokinetic/pharmacodynamic (PK/PD) outcome markers, drug resistance, PK variability, drug-drug interactions, assays, and TDM sampling strategies were summarized. Results Echinocandins demonstrate drug exposure-efficacy relationships, and maximum concentration/minimal inhibitory concentration ratio (Cmax/MIC) and area under the concentration-time curve/MIC ratio (AUC/MIC) are proposed PK/PD markers for clinical response. The relationship between drug exposure and toxicity remains poorly clarified. TDM could be valuable in patients at risk of low drug exposure, such as those with critical illness and/or obesity. TDM of echinocandins may also be useful in patients with moderate liver impairment, drug-drug interactions, hypoalbuminemia, and those undergoing extracorporeal membrane oxygenation, as these conditions are associated with altered exposure to caspofungin and/or micafungin. Assays are available to measure anidulafungin, micafungin, and caspofungin concentrations. A limited-sampling strategy for anidulafungin has been reported. Conclusion Echinocandin TDM should be considered in patients at known risk of suboptimal drug exposure. However, for implementing TDM, clinical validation of PK/PD targets is needed.

AIM This study investigates the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of linezolid in patients infected with multidrug-resistant (MDR) tuberculosis (TB). METHODS A pharmacometric model was developed including 244 timed linezolid concentration samples from 39 patients employing NONMEM 7.4. The probability of target attainment (PTA, PK/PD target: unbound (f) area-under-the-concentration-time-curve (AUC)/minimal inhibitory concentration (MIC) of 119) as well as a region-specific cumulative fraction of response (CFR) were estimated for different dosing regimens. RESULTS A one-compartment model with linear elimination with a clearance (CL) of 7.69 L/h (interindividual variability 34.1%), a volume of distribution (Vd) of 45.2 L and an absorption constant (KA) of 0.679 h-1 (interoccasion variability 143.7%) allometric scaled by weight best described the PK of linezolid. The PTA at an MIC of 0.5 mg/L was 55% or 97% if patients receiving 300 or 600 mg twice daily, respectively. CFRs varied greatly among populations and geographic regions. A desirable global CFR of ≥90% was achieved if linezolid was administered at a dose of 600 mg twice daily but not at a dose of 300 mg twice daily. CONCLUSION This study showed that a dose of 300 mg twice daily of linezolid might not be sufficient to treat MDR-TB patients from a PK/PD perspective. Thus, it might be recommendable to start with a higher dose of 600 mg twice daily to ensure PK/PD target attainment. Hereby, therapeutic drug monitoring and MIC determination should be performed to control PK/PD target attainment as linezolid shows high variability in its PK in the TB population.

Different types of zinc compounds were successfully encapsulated using the technique of spray drying. Maltodextrin, pea proteins, and titanium dioxide were the materials used as bulk materials. We investigated the effect of the total solids weight percentage and the ratios between different components (zinc to maltodextrin, zinc to protein, zinc to titanium dioxide, and protein to maltodextrin) on zinc bioavailability, assessed at various times points in an in vitro digestion. The following formulation characteristics were found to produce encapsulated zinc microcapsules with highest bioavailability (up to 85%): a zinc oxide to maltodextrin ratio of 0.3, a weight percentage of 9, and a maltodextrin to pea protein ratio of 3. Other types of zinc compounds, citrate, gluconate, sulfate, carbonate, and chloride produce an average bioavailability of 45%. A small addition of the ratio zinc and titanium dioxide of 2.2 causes a decrease in zinc bioavailability of about 25%. These spray-dried microparticles containing encapsulated iron can be used for food fortification with the purpose of treating iron deficiency.

Tuning the self-assembly of dendritic amphiphiles represents a major challenge for the design of advanced nanomaterials for biomimetic applications. The morphology of the final aggregates, in fact, critically depends on the primary structure of the dendritic building blocks as well as the environmental conditions. Here we report a new family of fluorinated Janus-type dendrimers (FJDs), based on a short-chain and branched fluorinated synthon with 27 magnetically equivalent fluorine atoms, linked to bis-MPA polyester dendrons of different generations. Increasing size, flexibility, and number of peripheral hydroxyl groups, we observed a peculiar self-assembly behavior in bulk and in aqueous media as a consequence of the subtle balance between their fluorinated and hydrophilic portions. The lowest generation FJDs formed spherical nanoparticles in water, e.g., micelles, showing a single 19F NMR peak with good signal-to-noise ratio and over time stability, making them promising as 19F-MRI traceable probes. The highest generation FJD, instead, presented an interesting morphological transition from multilamellar dendrimersomes to tubules as a consequence of a subtle balance of intra- and intermolecular forces that compete at the interface. Interestingly, a reduction of the local mobility of CF3 groups passing from dendrimersomes to tubules switches off the 19F NMR signal. The transition mechanism has been rationalized by coarse-grain simulations as well as demonstrated by using cosolvents of different nature (e.g., fluorinated) that promote conformational changes, ultimately reflected in the self-assembly behavior. Short and branched fluorinated chains have here been demonstrated as new moieties for the design of FJDs with tunable self-assembly behavior for potential applications as biocompatible 19F MRI probes in the construction of theranostic platforms. publishedVersion

Molecular imaging techniques are essential tools for better investigating biological processes and detecting disease biomarkers with improvement of both diagnosis and therapy monitoring. Often, a single imaging technique is not sufficient to obtain comprehensive information at different levels. Multimodal diagnostic probes are key tools to enable imaging across multiple scales. The direct registration of in vivo imaging markers with ex vivo imaging at the cellular level with a single probe is still challenging. Fluorinated (19F) probes have been increasingly showing promising potentialities for in vivo cell tracking by 19F-MRI. Here we present the unique features of a bioorthogonal 19F-probe that enables direct signal correlation of MRI with Raman imaging. In particular, we reveal the ability of PERFECTA, a superfluorinated molecule, to exhibit a remarkable intense Raman signal distinct from cell and tissue fingerprints. Therefore, PERFECTA combines in a single molecule excellent characteristics for both macroscopic in vivo 19F-MRI, across the whole body, and microscopic imaging at tissue and cellular levels by Raman imaging.

Sum-frequency generation imaging microscopy combined with compressive-sensing (CS-SFG) is a powerful micro-spectroscopic technique for probing interfaces and surfaces with a spatial resolution where contrast is based on the chemical functional groups. We reported the use of the CS-SFG technique to probe the electric field due to charge accumulation and the internal electric field in operating organic field-effect transistors (OFETs) with the aluminum oxide and octadecylphosphonic acid (ODPA) self-assembled monolayer as the gate dielectric layer and 2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT) as the semiconductor layer. In addition, the electric field behavior was discussed by a difference in the electric field induced SFG intensity between the open-circuit and the voltage application conditions. The SFG peak of CH stretching mode derived from methyl groups of ODPA and phenyl groups of DPh-BTBT could be observed at each interface of ODPA/DPh-BTBT or DPh-BTBT/Au, respectively. Moreover, the electric field induced SFG coming from ODPA/DPh-BTBT shows the presence of intense electric field due to charge injection and accumulation near the drain and source electrode edges under the operation of OFETs. Our studies show that the electric field-induced SFG imaging technique is useful for probing the local electric field distribution or charge accumulation behavior in OFETs under operating conditions.

According to the drug label, linezolid dosage adjustments are not needed in geriatric patients. Nevertheless, clinical evidence suggests that elderly patients may benefit from the use of reduced linezolid doses to limit drug overexposure. Here, we aimed to describe the results of the last 5 years of therapeutic drug monitoring of linezolid in our institution with a special focus on elderly patients.Linezolid therapeutic drug monitoring requests collected between January 2016 and June 2020 were considered. Linezolid trough concentrations were considered both as a continuous variable and as a categorical variable, clustering data according to the therapeutic range proposed by available literature (2, 2-8, and8 mg/L, respectively). Patients' age and sex were considered as categorical variables. Comparisons of linezolid trough concentrations between groups of patients stratified according to age were performed using an analysis of variance; comparisons in the frequency distributions were performed using the chi-squared test.From 2016 to 2020, we collected 3250 linezolid TDM requests. A highly significant, progressive increment in the linezolid trough concentrations was observed moving from patients aged50 years (5.8 ± 5.6 mg/L) to those aged90 years (16.6 ± 10.0 mg/L), with an overall increment of 30% per decade of age. Nearly 30%, 50%, and 65% of patients aged65 years, 65-80 years, and80 years, respectively, had supra-therapeutic linezolid trough concentrations at the first therapeutic drug monitoring assessment. This trend did not change significantly moving from 2016 to 2020.Elderly patients given linezolid at the conventional 600-mg twice-daily dose might be at a high risk of being overexposed to treatment, eventually increasing their risk to experience drug-related hematological toxicity. Reduced linezolid dosing schemes should be potentially considered in elderly patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring.

Neuroinflammation is involved in the pathogenesis of several neurologic disorders, including epilepsy. Both changes in the input/output functions of synaptic circuits and cell Ca2+ dysregulation participate in neuroinflammation, but their impact on neuron function in epilepsy is still poorly understood. Lipopolysaccharide (LPS), a toxic byproduct of bacterial lysis, has been extensively used to stimulate inflammatory responses both in vivo and in vitro. LPS stimulates Toll-like receptor 4, an important mediator of the brain innate immune response that contributes to neuroinflammation processes. Although we report that Toll-like receptor 4 is expressed in both excitatory and inhibitory mouse hippocampal neurons (both sexes), its chronic stimulation by LPS induces a selective increase in the excitatory synaptic strength, characterized by enhanced synchronous and asynchronous glutamate release mechanisms. This effect is accompanied by a change in short-term plasticity with decreased facilitation, decreased post-tetanic potentiation, and increased depression. Quantal analysis demonstrated that the effects of LPS on excitatory transmission are attributable to an increase in the probability of release associated with an overall increased expression of L-type voltage-gated Ca2+ channels that, at presynaptic terminals, abnormally contributes to evoked glutamate release. Overall, these changes contribute to the excitatory/inhibitory imbalance that scales up neuronal network activity under inflammatory conditions. These results provide new molecular clues for treating hyperexcitability of hippocampal circuits associated with neuroinflammation in epilepsy and other neurologic disorders. SIGNIFICANCE STATEMENT Neuroinflammation is thought to have a pathogenetic role in epilepsy, a disorder characterized by an imbalance between excitation/inhibition. Fine adjustment of network excitability and regulation of synaptic strength are both implicated in the homeostatic maintenance of physiological levels of neuronal activity. Here, we focused on the effects of chronic neuroinflammation induced by lipopolysaccharides on hippocampal glutamatergic and GABAergic synaptic transmission. Our results show that, on chronic stimulation with lipopolysaccharides, glutamatergic, but not GABAergic, neurons exhibit an enhanced synaptic strength and changes in short-term plasticity because of an increased glutamate release that results from an anomalous contribution of L-type Ca2+ channels to neurotransmitter release.

BACKGROUND Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings. METHODS Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. RESULTS Eleven HIV-positive patients prescribed carbamazepine or oxcarbazepine were identified. All the TDM evaluations for carbamazepine and oxcarbazepine that resulted were within the therapeutic ranges. TDM results of darunavir measured in these patients were comparable with values usually measured in the control group. Conversely, the trough concentrations for atazanavir and dolutegravir demonstrated significantly lower values when compared with values usually measured in HIV-infected patients not treated with antiepileptic drugs (190 ± 91 versus 546 ± 380 ng/mL; -65%, P < 0.001; 191 ± 78 versus 1096 ± 510 ng/mL; -83%, P < 0.001, respectively). CONCLUSIONS Co-administration of carbamazepine or oxcarbazepine with atazanavir or dolutegravir should be avoided owing to the potential risk of virological failure; in case of these 2 drugs, the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving alpha-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal alpha-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest alpha-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of alpha-synucleinopathy patients with isolated RBD might develop.

Summary: Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca2+ dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca2+ and associated with a reduced contribution of P/Q-type Ca2+ channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca2+ currents due to a decreased membrane targeting of the channel with unchanged total expression levels. Co-immunoprecipitation, pull-down assays, and proteomics reveal a specific and direct interaction of PRRT2 with P/Q-type Ca2+ channels. At presynaptic terminals lacking PRRT2, P/Q-type Ca2+ channels reduce their clustering at the active zone, with a corresponding decrease in the P/Q-dependent presynaptic Ca2+ signal. The data highlight the central role of PRRT2 in ensuring the physiological Ca2+ sensitivity of the release machinery at glutamatergic synapses.

Mutations in PRoline Rich Transmembrane protein 2 (PRRT2) cause pleiotropic syndromes including benign infantile epilepsy, paroxysmal kinesigenic dyskinesia, episodic ataxia, that share the paroxysmal character of the clinical manifestations. PRRT2 is a neuronal protein that plays multiple roles in the regulation of neuronal development, excitability, and neurotransmitter release. To better understand the physiopathology of these clinical phenotypes, we investigated PRRT2 interactome in mouse brain by a pulldown-based proteomic approach and identified α1 and α3 Na+/K+ ATPase (NKA) pumps as major PRRT2-binding proteins. We confirmed PRRT2 and NKA interaction by biochemical approaches and showed their colocalization at neuronal plasma membrane. The acute or constitutive inactivation of PRRT2 had a functional impact on NKA. While PRRT2-deficiency did not modify NKA expression and surface exposure, it caused an increased clustering of α3-NKA on the plasma membrane. Electrophysiological recordings showed that PRRT2-deficiency in primary neurons impaired NKA function during neuronal stimulation without affecting pump activity under resting conditions. Both phenotypes were fully normalized by re-expression of PRRT2 in PRRT2-deficient neurons. In addition, the NKA-dependent afterhyperpolarization that follows high-frequency firing was also reduced in PRRT2-silenced neurons. Taken together, these results demonstrate that PRRT2 is a physiological modulator of NKA function and suggest that an impaired NKA activity contributes to the hyperexcitability phenotype caused by PRRT2 deficiency.

Short-term exposures to indoor air contaminants can cause adverse health impacts and warrant a need for real-time measurements. The most common indoor pollutants are carbon dioxide (CO2), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), total volatile organic compounds (TVOCs), and particulate matter with a diameter of less than 2.5 μm (PM2.5). Several low-cost monitors for indoor air quality are commercially available; however, few of them are accurately tested. A stable, easy to use, and reproducible platform was developed in this paper. In these laboratory conditions, the comparison between the low-cost sensors and calculated concentration was shown to be linear (R2 of 0.980, 0.972, 0.990, 0.958, 0.987, and 0.816 and rs of 0.982, 0.985, 0.900, 0.924, 0.982, and 0.571 for PM2.5, CO2, CO, NO2, TVOC (ethylene), and O3 respectively). Laboratory conditions were used to test possible cross-interferences to the TVOC sensor; an increase of CO2, CO, and NO2 of 2500 ppm, 100 ppb, and 100 ppb respectively generated a change in the curve fit from linear to quadratic. A complete validation of a low-cost sensor was achieved by its application in a real indoor place. Good correlation between the reference methods and uHoo measurements of PM2.5, CO2, and O3 was achieved (rs = 0.765 to 0.894, 0.721 to 0.863, and 0.523 to 0.622 respectively).

A simple imaging add-on utilizing the combination of a relay lens and an optical grating to a nulling ellipsometer for the purpose of imaging and correcting angular distortion is designed, built, and tested. Image contrast is achieved on a standardized silicon wafer, graphene transferred on silicon wafer, a self-assembled monolayer of 1-octadecanethiol on gold, and a 1:1 mixture of dilauroylphosphatidylcholine / distearoylphosphatidylcholine (DLPC/DSPC) on copper. The configuration used in this paper corrects the angular distortion and depth of focus with a spatial resolution of 4.38 μm in the laser's incident direction and 7.81 μm in the direction that is perpendicular to the incident plane together with 3 Å of normal resolution while still maintaining a large field of view of at least 720 μm × 550 μm in focus without executing any line scanning, post-image reconstruction, or specially customized objective method. Better resolution is possibly attained with higher NA optics.

Background: ER- HER2+ BC is comprised of a heterogeneous mix of intrinsic BC subtypes which have differential responsiveness to preop HER2-directed therapies combined with chemotherapy. Patients (pts) with ER- HER2+ BC whose disease progressed while on or who had no response to preop HER2-directed therapy are uncommon and the mechanisms of resistance within this primary-refractory disease are unknown. We utilized RPPA-based protein pathway activation mapping to map the drug target signaling architecture in pts’ primary-refractory ER- HER2+ BCs to begin to assess mechanisms of resistance. Methods: Eight primary-refractory ER- HER2+ FFPE BC tissues obtained from 5 pts (preop biopsies n=4 and/or post-treatment surgical resection n=4) underwent laser capture microdissection to isolate pure tumor epithelium followed by RPPA-based analysis of the levels and/or activation/phosphorylation of approximately 130 key signaling proteins known to be involved in tumorigenesis and metastatic progression. Results: Pts were all treated with preop trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) with no response and/or with progression of disease. Three pts also received preop doxorubicin/cyclophosphamide without response. RPPA-based analysis revealed that post-TCHP surgical samples had higher activation of a number of drug targets including receptor tyrosine kinases (RTK) such as MET and ALK, as well as HER family signaling proteins phospho-HER3 and phospho-EGFR compared to the matched pre-TCHP samples. Conclusions: In these ER- HER2+ BCs that were primary-refractory to preop TCHP, in those pts with patient-matched pre/post treatment samples, activation of several potential resistance pathways such as alternative RKT signaling as well as EGFR and HER3 signaling was observed. These data are hypothesis-generating and require exploration in additional ER- HER2+ primary-refractory tissues. Citation Format: Mariaelena Pierobon, Maren K Levin, Elisa Baldelli, Leslie SL Kim, Lance Liotta, Emanuel F Petricoin, Joyce O'Shaughnessy. Patterns of protein expression and signaling assessed by reverse phase protein array (RPPA) in estrogen-receptor negative (ER-), HER2-amplified breast cancer (BC) that was primary-refractory to preoperative (preop) HER2-directed therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-31.

The direction and magnitude of surface dipoles directly affect the interfacial properties and can be tuned through molecular design. This article examines the effect of a hydrocarbon–fluorocarbon, ...

Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic. In this work, we have characterized the effect of SynI knockout (KO) in the regulation of GABA release dynamics. Using patch-clamp recordings in hippocampal slices, we demonstrate that the lack of SynI impairs synchronous GABA release via a reduction of the readily releasable SVs and, in parallel, increases asynchronous GABA release. The effects of SynI deletion on synchronous GABA release were occluded by ω-AgatoxinIVA, indicating the involvement of P/Q-type Ca2+channel-expressing neurons. Using in situ hybridization, we show that SynI is more expressed in parvalbumin (PV) interneurons, characterized by synchronous release, than in cholecystokinin or SOM interneurons, characterized by a more asynchronous release. Optogenetic activation of PV and SOM interneurons revealed a specific reduction of synchronous release in PV/SynIKO interneurons associated with an increased asynchronous release in SOM/SynIKO interneurons. The results demonstrate that SynI is differentially expressed in interneuron subpopulations, where it boosts synchronous and limits asynchronous GABA release.

International audience; The Aβ(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the Aβ(1-42) fibril formation in the presence of pyrimethanil, a widely used fungicide belonging to the anilinopyrimidine class. Our results evidenced a pro-aggregating effect of pyrimethanil on Aβ(1-42). Aβ(1-42) assemblies were successfully detected using conical nanopore coated with PEG. Using an analytical model, the large current blockades observed (>0.7) were assigned to species with size close to the sensing pore. The long dwell times (hundreds ms scale) were interpreted by the possible interactions amyloid/PEG using molecular dynamic simulation. Such interaction could leave until splitting phenomena of the dimer structure. Our work also evidences that the pyrimethanil induce an aggregation of Aβ(1-42) mechanism in two steps including the reorganization prior the elongation phase.

Global flaring volume exceeds 140 billion m³ annually and flares are a key source of particulate air pollution. During flowback operations subsequent to fracturing of a well, droplets of flowback water-with varying levels of dissolved salts-can be entrained in the flared gas. Despite the widespread prevalence of fracturing, very little is known about the properties of particle emissions from such flares. To study these properties, we used a laboratory pipe flare producing a turbulent diffusion flame without and with entrained droplets. Entrained droplets of deionized water, sodium chloride solution, and solutions representing two typical flowback waters in Canada (Cardium and Duvernay) were used. Three different gas compositions (consisting of C1 to C7 alkanes, carbon dioxide, and nitrogen) representative of flares in the upstream oil and gas sector in Alberta, Canada were studied. The results showed that the salt in the entrained flowback droplets increased the particle concentration by about one order of magnitude by forming freshly nucleated salt particles. Moreover, soot concentration increased as a result of entrained salt. Effective density results showed that small particles (300 nm) were mostly soot—a result also confirmed by transmission electron microscopy (TEM). Electron micrographs showed that the majority of particles were either individual salt particles or internally-mixed soot-salt particles. The inorganic salt particles mainly consisted of Na and Cl, the two most abundant elements in flowback water. Raman spectroscopy indicated that the salt had much less (or no) impact on graphitic nanostructure of soot, while the fuel blend had a significant effect. The results of this study are significant as they reveal that current emission inventories based on flaring of gases only may underestimate soot emissions from flares with entrained droplets.

An important issue for developing a molecular-level mechanism of heterogeneous interactions at the aqueous interface is determining changes in the interface with changes in the bulk composition. Development of the nonlinear spectroscopy, sum frequency generation (SFG) provides a technique to probe these changes. Several molecular and ionic solutes have been used to investigate changes in the structure of the aqueous interface. Molecular solutes include glycerol and ammonia. Ionic and associated ion complexes include sulfuric acid as well as alkali sulfate and bisulfate salts. Molecular solutes and associated ion complexes penetrate to the top monolayer of the aqueous-air interface displacing water from the interface. Specifically, the conjectured ammonia-water complex is observed with ammonia tilted, on average, 25-38° from the normal. Ionic solutes generate a double layer in the interfacial region due to the differential distribution of anions and cations near the interface. The strength of the double layer is dependent on ion size and charge. Due to the extreme size of the proton, the strongest field is generated by acidic solutes. As the ionic solute concentration increases, associated ion pairs form and these penetrate to the top monolayer. These results have wide implications because the aqueous interface is ubiquitous in atmospheric and biological systems.

Objectives. Some DNA viruses, such as BKPyV, are capable of inducing neoplastic transformation in human tissues through still unclear mechanisms. The goal of this study is to investigate the carcinogenic potential of BK polyomavirus (BKPyV) in human embryonic kidney 293 (Hek293) cells, dissecting the molecular mechanism that determines the neoplastic transformation. Materials and Methods. BKPyV, isolated from urine samples of infected patients, was used to infect monolayers of Hek293 cells. Subsequently, intracellular redox changes, GSH/GSSH concentration by HPLC, and reactive oxygen/nitrogen species (ROS/RNS) production were monitored. Moreover, to understand the signaling pathway underlying the neoplastic transformation, the redox-sensitive HFS1-Hsp27 molecular axis was examined using the flavonoid quercetin and polishort hairpin RNA technologies. Results. The data obtained show that while BKPyV replication is closely linked to the transcription factor p53, the increase in Hek293 cell proliferation is due to the activation of the signaling pathway mediated by HSF1-Hsp27. In fact, its inhibition blocks viral replication and cell growth, respectively. Conclusions. The HSF1-Hsp27 signaling pathway is involved in BKPyV infection and cellular replication and its activation, which could be involved in cell transformation.

Objectives: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens. Methods: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan–Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed. Results: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30–43) years vs. 33 (IQR 27–39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257–421) cells/μL vs. 447 (IQR 347–580) cells/μL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92–4.74) log10 copies/mL vs. 4.23 (IQR 3.81–4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89–5.80], for toxicity (RH 2.23; 95% CI 1.05–4.73) for intolerance (RH 5.17; 95% CI 2.66–10.07) and for proactive switch (RH 10.96; 95% CI 3.17–37.87) than those starting RPV. Conclusions: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.

Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. In this respect, azobenzene-based photoswitches are promising nanoscale tools for neuronal photostimulation. Here we engineered a light-sensitive azobenzene compound (Ziapin2) that stably partitions into the plasma membrane and causes its thinning through trans-dimerization in the dark, resulting in an increased membrane capacitance at steady state. We demonstrated that in neurons loaded with the compound, millisecond pulses of visible light induce a transient hyperpolarization followed by a delayed depolarization that triggers action potential firing. These effects are persistent and can be evoked in vivo up to 7 days, proving the potential of Ziapin2 for the modulation of membrane capacitance in the millisecond timescale, without directly affecting ion channels or local temperature. Light-sensitive azobenzene compounds can be engineered to stably partition into the plasma membrane, thus causing its thinning in the dark and relaxation upon light stimulation. In neurons, the resulting light-dependent change in membrane capacitance induces a transient hyperpolarization followed by rebound depolarization and action potential firing.

The exposure to linezolid is characterized by a large inter-individual variability; age, renal dysfunction and body weight explain this variability only to a limited extent and a considerable portion of it remains unexplained; therefore, we decided to investigate the role of individual genetic background focusing in particular on the risk of linezolid underexposure. 191 patients in therapy with linezolid at the standard dose of 600 mg twice daily were considered. Linezolid plasma concentration was determined at the steady state and classified as “below”, “within” or “above” reference range. Genetic polymorphisms for ATP Binding Cassette Subfamily B Member 1 (ABCB1), Cytochrome P450 (CYP) enzymes CYP3A4 and CYP3A5, and Cytochrome P450 Oxidoreductase (POR) were investigated. Age significantly correlated with drug exposure, and patients CYP3A5 expressers (GA and AA) were found at high risk to be underexposed to the drug when treated at standard dose. This association was confirmed even after correction with age. No association was found with ABCB1 polymorphism. Our data suggest that CYP3A5 polymorphisms might significantly affect linezolid disposition, putting patients at higher risk to be underexposed, while P-glycoprotein polymorphism seem not to play any role.

Nanoparticle (NP) self-assembly has led to the fabrication of an array of functional nanoscale systems, having diverse architectures and functionalities. In this perspective, we discuss the design and application of NP suprastructures (SPs) characterized by nanoconfined compartments in their self-assembled framework, providing an overview about SP synthetic strategies reported to date and the role of their confined nanocavities in applications in several high-end fields. We also set to give our contribution towards the formation of more advanced nanocompartmentalized SPs able to work in dynamic manners, discussing the opportunities of further advances in NP self-assembly and SP research., This perspective gives an outlook on the design of interparticle confined nanocavities in self-assembled NP systems and their functional relevance.

Oleuropein, a glycosylated secoiridoid present in olive leaves, is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 &mu, M and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells, because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant.

Background Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling. Objectives To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA). Methods We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets. Results A total of 41 participants (59% male) median age of 75 years (IQR 63–79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6–15 mL/min, in whom suboptimal PTA of ≤71% is predicted. Conclusions Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is

Nanocomposite coatings, i.e., a combination of nanocompounds, and a polymer matrix together with suitable additives and solvents is a very versatile method for producing multifunctional coatings. Some of the most desired coating properties have a high repellency to liquids (e.g., superhydrophobic and/or superoleophobic) and electrical and thermal conductivities. From a practical perspective, coatings that can be sprayed are very suitable for large-scale production, conformity, and reduced time and cost. Carbon-based, metallic, and ceramic are the three groups of nanocompounds commonly used to formulate spray-on nanocomposite coatings. In this invited feature article, we discuss the applications, advantages, and challenges of using such nanocompounds to produce coatings with good water repellency or/and elevated electrical or/and thermal conductivities. We also discuss the role of additives and solvents briefly in relation to the properties of the coatings. Important spraying parameters, such as stand-off distance and its influence on the final coating properties, will also be examined. Our overall aim is to provide a guideline for the production of practical multifunctional nanocomposites utilizing carbon-based, metallic, or ceramic nanoparticles or nanofibers that covers both aspects of in-air wettability and conductivity under one umbrella.

Purpose: Low levels of ghosting are found during quality control of digital mammography (DM). In digital breast tomosynthesis (DBT) mode, the x-ray detector is not cleared during the series of exposures potentially leading to ghosting issues. Methods: The ghosting image factor (GIF) was calculated for systems from three manufacturers as follows. A 45 mm thick polymethyl methacrylate (PMMA) block covering half the detector was imaged, followed by the PMMA block plus 0.1 mm thick aluminium sheet centred on the block, this time positioned to fully cover the detector. This was undertaken for (1) DM and (2) between separate DBT scans. Inter-projection ghosting (3) was measured by moving the PMMA block from covering half the detector to covering the whole detector after the first projection. In method (4), a 3 mm thick aluminium plate with a 0.1 mm thick aluminium sheet on top was placed on the compression paddle at 100 mm above the breast covering half of the detector. Results: The GIF measured via test (1) and (2) was lower than the 0.3 tolerance set in the European guidelines for DM, however higher values were found for one system in DBT mode. Test 3, inter-projection GIF values were between 0.08 and 0.89, mostly above 0.3. Test 4 was a practical method and gave larger GIF values of between 1.07 and 8.01. Conclusions Ghosting factors measured between projections are considerably higher than the GIF measured between separate DBT scans. We propose a simple method using an aluminium plate to estimate the GIF.

The structures of novel double-strand imidazolium iodide ionic liquids (ILs)-based lipid in the water phase have been studied in this research. We report the effect of alkyl chain length of 1,3-dimethyl-4,5-dialkyl-imidazolium iodide([2(Me)2(Cn)im]I, n = 7, 11, 15) ILs on their structures in the aqueous solution by molecular dynamics simulation. The structure details of IL clusters lead to the various aggregation forms by increasing the alkyl chain length of ILs. The ILs with n = 7 and 11 can help develop micelle structures of different sizes, and the IL with n = 15, the benign IL, feasible to develop lipidlike vesicle. To obtain more details about bilayer properties, [2(Me)2(C15)im]I IL is investigated by different IL/water ratios in this study exclusively. The [2(Me)2(C15)im]I IL bilayer thickness and deuterium order parameters are compared with lipid membrane, and they reveal a small difference. The energies, radial distribution functions, spatial distribution function, cluster size, number density, an...

Sum frequency generation (SFG) images of microcontact patterned self-assembled alkanethiol monolayers on metal surfaces were analyzed by factor analysis (FA) to determine the spatial distribution of the patterned monolayers over the images. Additionally, each significant abstract factor produced by FA was assessed to determine the information contained within it. These results indicate that FA of the SFG spectra is a promising method to determine the composition and identities of mixed alkanethiol systems that show different vibrational spectra and image contrast. Factor analysis has successfully been applied to SFG images obtained with low signals, which reduces the time required for full spectral SFG imaging.

Among globally relevant combustion sources, such as diesel emission and biomass burning, gas flaring remains the most uncertain. In this study, small-scale turbulent gas flaring was used to characterize particulate emissions produced under different operating conditions, such as various burner diameters and exit velocities. The composition of the fuel was also varied by modifying the percentage of methane, ethane, propane, butane, N2, and CO2, which are the predominant constituents in the upstream oil and gas industry. A broad suite of physical, chemical, and microscopic techniques was employed for analysis, and scanning electron microscopy showed the generated soot agglomerates to be composed of primary spherules that were 30 ± 10 nm in diameter. Additionally, high-resolution transmission electron microscopy, used to determine the length, tortuosity, and separation of individual graphene fringes on the primary particles, revealed a fullerenic, multiple-nuclei internal structure. Single-particle analysis revealed the dominance of elemental carbon vs. oxidized and metal-contaminated particles, and infrared spectroscopy showed the presence of alkanes and aromatics with oxygenated compounds. Intercomparing the microstructure and the composition, we also concluded that the vast majority of particles are hydrophobic.

Staphylococcus aureus infections associated with implanted medical devices are difficult to treat and require long-lasting antibiotic therapies, especially when device removal is not possible or easy such as in the case of joint prostheses. Biofilm formation is a major cause of treatment failure and infection recurrence. This study aimed to test, for the first time, the in vitro combination of tedizolid plus rifampicin on methicillin-sensitive (MSSA ATCC 6538) and methicillin-resistant (MRSA ATCC 43300) S. aureus mature biofilm. Here, we demonstrated that the combination of tedizolid with rifampicin significantly disaggregated pre-formed biofilm of both strains, reduced their metabolic activity and exerted bactericidal activity at clinically meaningful concentrations. Notably, tedizolid was able to completely prevent the emergence of resistance to rifampicin. Moreover these effects were similar to those obtained with daptomycin plus rifampicin, a well-known and widely used combination. Preliminary results on some MRSA clinical isolates confirmed the efficacy of this combination in reducing biofilm biomass and preventing rifampicin resistance onset. Further in vivo studies are needed to confirm the validity of this promising therapeutic option that can be useful against biofilm-associated S. aureus infections.

Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to VIRO-immunoclinical events. Results Pre-ART HIV DNA [median (IQR): 10 € 702 (3397-36 € 632) copies/10 6 CD4+ T cells] was correlated with pre-ART HIV RNA [R 2 = +0.44, (P < 0.0001)], CD4+ T cells [R 2 = '0.58, (P < 0.0001)] and CD4/CD8 ratio [R 2 = '0.48, (P < 0.0001)], while weaker correlations were observed with CD8+ T cells (R 2 = '0.20, P = 0.01), IL-6 (R 2 = +0.16, P = 0.002) and soluble CD14 (R 2 = +0.09, P = 0.05). Patients with higher pre-ART HIV DNA showed lower rate and delayed VIROlogical response (defined as HIV RNA ≤50 copies/mL), compared with those having lower HIV DNA (67.2% for >10 € 000, 81.1% for 1000-10 € 000 and 86.4% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of VIROlogical rebound (defined as HIV RNA >50 copies/mL) by 24 months (17.2% for >10 € 000, 7.4% for 1000-10 € 000 and 4.3% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0048). Adjusted HRs of all VIROlogical rebound definitions confirmed these findings (P ≤ 0.02). Conclusions Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of VIROlogical suppression (≤50 copies/mL).

Objectives Our primary aim was to study diabetes mellitus (DM) arising during combination ART (cART) and to attempt to identify associations between these cases and triglycerides (TRG) and the TRG to HDL-cholesterol (TRG/HDL) ratio. Our secondary aim was to analyse the association between DM development and hepatic fibrosis. Methods This was a retrospective cohort study. Patients from the Icona Foundation study initiating first-line cART between 1997 and 2013 were selected and observed until new-onset DM or most recent clinical follow-up. The predictive value of TRG and TRG/HDL ratio levels on DM was evaluated using multivariable Poisson regression models. Results Three-thousand, five-hundred and forty-six patients (males, 73.7%; median age, 38 years; median BMI, 23.1 kg/m2; and hepatitis C virus antibody positive, 22.1%) were included. Of these, 80 developed DM over 13 911 person-years of follow-up (PYFU), corresponding to 5.7 cases per 1000 PYFU (95% CI = 4.6–7.1). At multivariable analysis, latest TRG/HDL ratio, when high, was associated with significant increases in DM risk [relative risk (RR) = 1.63; 95% CI = 1.32–2.01 per 10 points higher], while current TRG, in contrast, was associated with new-onset DM only at crude analysis. Advanced liver fibrosis (defined as fibrosis-4 index >3.25) was also shown to be an independent risk factor for DM (RR = 2.91; 95% CI = 1.10–7.72). Conclusions High TRG/HDL ratio predicted risk of new-onset DM, independently of other traditional risk factors. Furthermore, our findings suggest that advanced hepatic fibrosis, estimated using the fibrosis-4 score, could provide an additional predictor for DM.

Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management.

The striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase involved in synaptic transmission. The current hypothesis on STEP function holds that it opposes synaptic strengthening by dephosphorylating and inactivating key neuronal proteins involved in synaptic plasticity and intracellular signaling, such as the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. Although STEP has a predominant role at the post-synaptic level, it is also expressed in nerve terminals. To better investigate its physiological role at the presynaptic level, we functionally investigated brain synaptosomes and autaptic hippocampal neurons from STEP knockout (KO) mice. Synaptosomes purified from mutant mice were characterized by an increased basal and evoked glutamate release compared with wild-type animals. Under resting conditions, STEP KO synaptosomes displayed increased cytosolic Ca2+ levels accompanied by an enhanced basal activity of Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and hyperphosphorylation of synapsin I at CaMKII sites. Moreover, STEP KO hippocampal neurons exhibit an increase of excitatory synaptic strength attributable to an increased size of the readily releasable pool of synaptic vesicles. These results provide new evidence that STEP plays an important role at nerve terminals in the regulation of Ca2+ homeostasis and neurotransmitter release.

Background An enzymatic immunoassay is under development by ARK Diagnostics, Inc for the quantification of plasma concentrations of linezolid (LZD). In this study, the authors aimed to assess the performance of this immunoassay using a validated high-performance liquid chromatography (HPLC) ultraviolet method as reference. Methods Within- and between-day in vitro inaccuracy and imprecision of the ARK LZD assay were firstly tested using spiked quality controls (QC) provided by the kit manufacturer. Subsequently, the performance of the immunoassay was verified in vivo by analyzing 170 trough LZD plasma samples from patients on antibiotic therapy. Results Imprecision of the spiked QCs resulted in every instance less than 7.0% and the inaccuracy ranged from -1.5% to 6.6%. The linear correlation between the 2 methods was documented by the Pearson analysis of plasma samples from patients on LZD therapy (coefficient = 0.9619). By Bland-Altman comparison, 8.2% of the patient samples resulted out of the limits ranging from -27.0% to +33.5%, with most of them having LZD concentrations exceeding 10 mg/L. Conclusions Acceptable analytical performance of the ARK LZD immunoassay has been demonstrated both with spiked QC and patients' samples, making it a viable alternative to HPLC for the therapeutic drug monitoring of LZD in clinical practice in laboratory hospitals that do not have HPLC equipment.

Viral nanoparticles in gastric and intestinal fluids: evaluation of digestion, denaturation, aggregation and protein corona formation., Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical (i.e. digestion of the polypeptides) stability of CPMV and its empty virus-like particles (eVLPs) in conditions resembling the gastrointestinal fluids were evaluated. The nanoparticles were incubated in various simulated gastric and intestinal fluids and in pig gastric and intestinal fluids. CPMV and eVLPs had similar stabilities. In simulated gastric media, they were stable at pH ≥ 2.5. At lower pH destabilisation of the particle structure occurred, which, in turn, rendered the polypeptides extremely sensitive to pepsin digestion. However, both CPMV and eVLPs were stable in simulated intestinal fluids, in pig gastric fluids and in pig intestinal fluids. Thus CPMV, despite being a protein-based nanoparticle, was much more resistant to the harsh GI conditions than soluble proteins. Remarkably, both CPMV and eVLPs incubated in pig gastric and intestinal fluids were not subject to protein adsorption, with no formation of a detectable protein corona. The lack of a protein corona on CPMV and eVLP surfaces in GI fluids would imply that, if orally administered, these nanoparticles could maintain their native surface characteristics; thus, their biological interactions would remain predictable and unchanged. In summary, CPMV and eVLPs can be considered promising nanocarriers for applications requiring oral delivery, given their chemical, physical and colloidal stability and lack of protein adsorption from the environment in most of the tested conditions.

Nanocellulose is of growing interest due to its great potential in many value-added applications and its unique characteristics. However, conventional methods for nanocellulose isolation are challenged by various economic and environmental concerns. With the use of recyclable oxalic acid dihydrate (OAD), this study demonstrated the rapid, high-yield production of lignin-containing cellulose nanocrystals (LCNCs) from thermomechanical pulp (TMP). Serving as the sole solvent and reactant, molten OAD effectively hydrolyzed TMP within 30 min at 110 °C, leading to complete removal of hemicellulose (97 %) but retaining most of the cellulose (93 %) and lignin (97 %). This modified TMP can be converted into LCNCs with a high overall yield of >70 % via microfluidization. The LCNCs possessed satisfactory thermal stability and exhibited a nanoscale morphology of highly uniform cellulose nanocrystals (7.0 nm in width, 3.9 nm in height, 200–300 nm in length, and 72 % in crystallinity), randomly implanted by lignin aggregates. The unreacted OAD could also be readily recycled via crystallization from the post-hydrolysis mixture. The recycled OAD showed good performance retention for at least 4 cycles, indicating its suitability for continuous TMP hydrolysis. Further life cycle assessment suggested that the recycling potential could reduce the global warming potential and energy use by 48 % and 47 %, respectively. Overall, it was apparent that recycling molten OAD provided a promising approach to rapidly make clean, high-yield LCNCs with low energy use and improved reagent utilization.

Gas flaring is a common practice in the oil and gas industry, where droplets of flowback water with varying levels of dissolved salts (mainly composed of sodium and chloride) often become entrained in the flared gas. In this study, we examine the mixing state of the aerosol produced by a laboratory flare with and without entrained droplets of sodium chloride solutions. The resultant aerosol is cross-examined using several different methods, including: transmission electron microscopy (TEM), tandem measurements using a CPMA and a differential mobility analyzer (DMA), tandem measurements using a centrifugal particle mass analyzer (CPMA) and a single particle soot photometer (SP2), and Raman spectroscopy. A focus is placed on two-dimensional distributions of properties and the kind of morphological information contained therein. The TEM and CPMA-SP2 measurements both show that the majority of soot particles were internally mixed with salt, while TEM and CPMA-DMA measurements indicate that there are also a large number of isolated salt particles.

The carbon soot has generally negative connotation due to the adverse impact on the human health and ambient environment. Most of the studies involving soot analysis focus on the need of preventing or reducing the sources of soot production. However, if the atmospheric soot aerosols are capable of repelling the ambient water vapor and thus impeding the water film formation on the soot particles’ outer shell, they can be considered as competitive and cost-effective candidates for the development of multifunctional non-wettable coatings. The physicochemistry of the soot, particularly the surface oxidation, the presence of heteroatoms and the degree of surface heterogeneity, regulates its chemical non-polarity and hygroscopicity. Appropriately selecting the types of soot sources facilitates the material’s recycling into a liquid-repellent tool with potential applicability in cryobiology, medicine, water purification devices, desalination systems, passive anti-bioadhesive and icephobic surfaces. This review article summarizes for the first time the main soot aerosol patterns based on their water uptake and provides detailed guidelines for the choice of suitable coating fabrication protocol and successive chemical processing. The latter are determinative factors in designing mechanically robust soot withstanding the impact of gusty winds, water jetting, abrasion or finger wiping. Finally, the state-of-the-art in the practical relevance of the hydrophobic soot is discussed, while the existing limitations and the future trends in the soot coatings technology are outlined.