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The integration of biocatalysts within metal-organic frameworks (MOFs) is attracting growing interest due to its potential to both enhance biocatalyst stability and sustain biocatalyst activity in organic solvents. However, the factors that facilitate the post-synthetic infiltration of such large molecules into MOF pores remain unclear. This systematic study enabled the identification of the influence of biocatalyst molecular size, molecular weight and affinity on the uptake by an archetypal MOF, NU-1000. We analyzed a range of six biocatalysts with molecular weights from 1.9 kDa to 44.4 kDa, respectively. By employing a combination of fluorescence tagging and 3D-STED confocal laser scanning microscopy, we distinguished between biocatalysts that were internalized within the MOF pores and those sterically excluded. The catalytic functions of the biocatalysts hosted within the MOF were investigated and found to show strong variations relative to the solvated case, ranging from a two-fold increase to a strong decrease., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

In downstream processing, the intricate nature of the interactions between biomolecules and adsorbent materials presents a significant challenge in the prediction of their binding and elution behaviors. This complexity is further heightened in multi-modal chromatography (MMC), which employs two distinct binding mechanisms. To gain a deeper understanding of the involved interactions, simulating the adsorption of biomolecules on resin surfaces is a focal point of ongoing research. However, previous studies often simplified the adsorbent surface, modeling it as a flat or slightly curved plane without including a realistic backbone structure. Here, we introduce and validate two novel workflows aimed at predicting peptide binding behaviors in MMC, specifically targeting methacrylate-based resins. Our first achievement was the development of an all-atom model of a commercial MMC resin surface, incorporating its polymethacrylic backbone. Furthermore, we established and tested a workflow for rapid calculations of binding free energies (ΔG) with 10 linear peptides as target molecules. These ΔG calculations were effectively used to predict Langmuir constants, achieving a high coefficient of determination (R²) of 0.96. In subsequent benchmarking tests, our model outperformed established, simpler resin surface models in terms of predictive capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This work introduces a new sustainable alternative of powdered activated carbon (PAC) - magnetically harvestable and reusable after regeneration via inductive heating - for the adsorptive removal of organic micropollutants (OMP) from secondary wastewater effluents. For this purpose, two commercial PACs - lignite "L" (1187 m 2 /g) and coconut "C"-based (1524 m 2 /g) - were modified with magnetic iron oxide following two different synthesis approaches: infiltration ("infiltr") and surface deposition ("depos") route. The resulting magnetic powdered activated carbons (mPAC) and their precursor PACs were fully characterized before application. The iron oxide content of the modified "L" and "C" samples was ∼30 % and ∼20 %, respectively. Iron oxide gives the PAC beneficial magnetic properties for easy magnetic separation and simultaneously acts as an inductively heatable agent for the carbon regeneration. The infiltrated samples displayed better inductive heating performance and regeneration than their deposited counterparts. Tests with real wastewater showed fast adsorption kinetics of the organic load following the pseudo-second-order kinetic model. Adsorption isotherms were compliant with the Freundlich isotherm model. Sample "L-infiltr" had the best overall adsorption performance throughout 5 reuse cycles when intermediately inductively regenerated (<3 % drop in organics removal per cycle with intermediate regeneration vs. ∼10 % drop per cycle without regeneration). The treated supernatant was additionally tested for 31 representative organic micropollutants and their transformation products (pharmaceuticals, personal care products, industrial chemicals, etc.), where 26 OMPs had consistently high removal (>85 %) throughout 5 cycles with intermediate regeneration and for 28 OMPs the total adsorption efficiency dropped by <5 % after 5 cycles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Understanding the neural correlates of consciousness has important ramifications for the theoretical understanding of consciousness and for clinical anaesthesia. A major limitation of prior studies is the use of responsiveness as an index of consciousness. We identified a collection of measures derived from unresponsive subjects and more specifically their association with consciousness (any subjective experience) or connectedness (specific experience of environmental stimuli)., Methods: Using published data generated through the UNderstanding Consciousness Connectedness and Intra-Operative Unresponsiveness Study (NCT03284307), we evaluated 10 previously published resting-state EEG-based measures that were derived using unresponsiveness as a proxy for unconsciousness. Measures were tested across dexmedetomidine and propofol sedation and natural sleep. These markers represent the complexity, connectivity, cross-frequency coupling, graph theory, and power spectrum measures., Results: Although many of the proposed markers were associated with consciousness per se (reported subjective experience), none were specific to consciousness alone; rather, each was also associated with connectedness (i.e. awareness of the environment). In addition, multiple markers showed no association with consciousness and were associated only with connectedness. Of the markers tested, loss of normalised-symbolic transfer entropy (front to back) was associated with connectedness across all three experimental conditions, whereas the transition from disconnected consciousness to unconsciousness was associated with significant decreases in permutation entropy and spectral exponent (P<0.05 for all conditions)., Conclusions: None of the proposed EEG-based neural correlates of unresponsiveness corresponded solely to consciousness, highlighting the need for a more conservative use of the term (un)consciousness when assessing unresponsive participants., Clinical Trial Registration: NCT03284307., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

In the 1960s, chromatography processes were revolutionized by the invention of simulated moving bed chromatography. This method not only enhances the separation performance and resin utilization in comparison to batch-chromatography, it has also a much lower buffer consumption. While simulated moving bed chromatography nowadays is applied for a wide range of industrial applications, it was never transferred to the micro-scale (in regards to column and system volume). In our opinion a micro simulated moving bed chromatography system (µSMB) would be a useful tool for many applications, ranging from early process development and long term studies to downstream processing of speciality products. We implemented such a µSMB with a 3D printed central rotary valve and a microfluidic flow controller as flow source. We tested the system with a four zone open loop setup for the separation of bovine serum albumin and ammonium sulfate with size exclusion chromatography. We used four process points and could achieve desalting levels of BSA ranging from 94% to 99%, with yields ranging form 65% to 88%. Thus, we were able to achieve comparable results to common lab scale processes. With a total dead volume of 358 µL, including all sensors, connections and the valve, this is, to the best of our knowledge, the smallest SMB system that was ever built and we were able to perform experiments with feed flow rates reaching as low as 15 µL/min., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The neural mechanisms through which individuals lose sensory awareness of their environment during anesthesia remains poorly understood despite being of vital importance to the field. Prior research has not distinguished between sensory awareness of the environment (connectedness) and consciousness itself. In the current study, we investigated the neural correlates of sensory awareness by contrasting neural responses to an auditory roving oddball paradigm during consciousness with sensory awareness (connected consciousness) and consciousness without sensory awareness (disconnected consciousness). These states were captured using a serial awakening paradigm with the sedative alpha2 adrenergic agonist dexmedetomidine, chosen based on our published hypothesis that suppression of noradrenaline signaling is key to induce a state of sensory disconnection. High-density electroencephalography was recorded from 18 human subjects before and after administration of dexmedetomidine. By investigating event-related potentials and taking advantage of advances in Dynamic Causal Modeling (DCM), we assessed alterations in effective connectivity between nodes of a previously established auditory processing network. We found that during disconnected consciousness, the scalp-level response to standard tones produced a P3 response that was absent during connected consciousness. This P3 response resembled the response to oddball tones seen in connected consciousness. DCM showed that disconnection produced increases in standard tone feedback signaling throughout the auditory network. Simulation analyses showed that these changes in connectivity, most notably the increase in feedback from right superior temporal gyrus to right A1, can explain the new P3 response. Together these findings show that during disconnected consciousness there is a disruption of normal predictive coding processes, so that all incoming auditory stimuli become similarly surprising., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: How conscious experience becomes disconnected from the environment, or disappears, across arousal states is unknown. We sought to identify the neural correlates of sensory disconnection and unconsciousness using a novel serial awakening paradigm., Methods: Volunteers were recruited for sedation with dexmedetomidine i.v., propofol i.v., or natural sleep with high-density EEG monitoring and serial awakenings to establish whether subjects were in states of disconnected consciousness or unconsciousness in the preceding 20 s. The primary outcome was classification of conscious states by occipital delta power (0.5-4 Hz). Secondary analyses included derivation (dexmedetomidine) and validation (sleep/propofol) studies of EEG signatures of conscious states., Results: Occipital delta power differentiated disconnected and unconscious states for dexmedetomidine (area under the curve [AUC] for receiver operating characteristic 0.605 [95% confidence interval {CI}: 0.516; 0.694]) but not for sleep/propofol (AUC 0.512 [95% CI: 0.380; 0.645]). Distinct source localised signatures of sensory disconnection (AUC 0.999 [95% CI: 0.9954; 1.0000]) and unconsciousness (AUC 0.972 [95% CI: 0.9507; 0.9879]) were identified using support vector machine classification of dexmedetomidine data. These findings generalised to sleep/propofol (validation data set: sensory disconnection [AUC 0.743 {95% CI: 0.6784; 0.8050}]) and unconsciousness (AUC 0.622 [95% CI: 0.5176; 0.7238]). We identified that sensory disconnection was associated with broad spatial and spectral changes. In contrast, unconsciousness was associated with focal decreases in activity in anterior and posterior cingulate cortices., Conclusions: These findings may enable novel monitors of the anaesthetic state that can distinguish sensory disconnection and unconsciousness, and these may provide novel insights into the biology of arousal., Clinical Trial Registration: NCT03284307., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Fully exploiting the potential of enzymes in cell-free biocatalysis requires stabilization of the catalytically active proteins and their integration into efficient reactor systems. Although in recent years initial steps towards the immobilization of such biomolecules in metal-organic frameworks (MOFs) have been taken, these demonstrations have been limited to batch experiments and to aqueous conditions. Here we demonstrate a MOF-based continuous flow enzyme reactor system, with high productivity and stability, which is also suitable for organic solvents. Under aqueous conditions, the stability of the enzyme was increased 30-fold, and the space-time yield exceeded that obtained with other enzyme immobilization strategies by an order of magnitude. Importantly, the infiltration of the proteins into the MOF did not require additional functionalization, thus allowing for time- and cost-efficient fabrication of the biocatalysts using label-free enzymes., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Phase change materials (PCMs) are an effective thermal mass and their integration into the structure of a building can reduce the ongoing costs of building operation, such as daily heating/cooling. PCMs as a thermal mass can absorb and retard heat loss to the building interior, maintaining comfort in the building. Although a large number of PCMs have been reported in the literature, only a handful of them, with their respective advantages and disadvantages, are suitable for building wall construction. Based on the information available in the literature, a critical evaluation of PCMs was performed in this paper, focusing on two aspects: (i) PCMs for building wall applications and (ii) the inclusion of PCMs in building wall applications. Four different PCMs, namely paraffin wax, fatty acids, hydrated salts, and butyl stearate, were identified as being the most suitable for building wall applications and these are explained in detail in terms of their physical and thermal properties. Although there are several PCM encapsulation techniques, the direct application of PCM in concrete admixtures is the most economical method to keep costs within manageable limits. However, care should be taken to ensure that PCM does not leak or drip from the building wall.

Herein, a simple model setup is presented to spray fine liquid droplets containing nanoparticles in an air stream transporting this toward a filter material. The nanoparticles are made of silica and tagged with a fluorescent dye in order to render the trace of the particles easily visible. The silica nanoparticles, in a first approximation, mimic virus (severe acute respiratory syndrome coronavirus 2) particles. The setup is used to evaluate different tissues, nowadays, in times of the coronavirus pandemic, commonly used as facemasks, with regard to their particle retention capability. The setup enables adjusting different "breathing scenarios" by adjusting the gas flow speed and, thereby, to compare the filter performance for these scenarios. The effective penetration of particles can be monitored via fluorescence intensity measurements and is visualized via scanning electron micrographs and photographs under UV light. Ultimately, a strong increase of particle penetration in various mask materials as function of flow speed of the droplets is observed and an ultimate retention is only observed for FFP3 and FFP2 masks., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Materials Technologies published by Wiley‐VCH GmbH.)

Background: Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium., Methods: A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity., Results: GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001)., Conclusions: The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation., Clinical Trial Registration: NCT02926417 and NCT03124303., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Electroencephalography signatures of amyloid-β, tau and neurodegenerative pathologies would aid in screening for, tracking progression of, and critically, understanding the pathogenesis of dementia. We hypothesized that slowing of the alpha peak frequency, as a signature of hyperpolarization-activated cyclic nucleotide gated 'pacemaker' channel activity, would correlate with amyloid and tau pathology burden measured by amyloid (Pittsburgh Compound B) and tau (MK-6240) positron emission tomography or CSF biomarkers. We also hypothesized that EEG power would be associated with neurodegeneration (CSF neurofilament light and hippocampal volume). Wakeful high-density EEG data were collected from 53 subjects. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency [Pittsburgh Compound B (+) vs. Pittsburgh Compound B (-) subjects, P  = 0.039 and MK-6240 (+) vs. MK-6240 (-) subjects, P  = 0.019]. Furthermore, slowing in the peak alpha frequency correlated with CSF Aβ 42/40 ratio ( r 2 = 0.270; P  = 0.003), phosphoTau (pTau 181 , r 2 = 0.290; P  = 0.001) and pTau 181 /Aβ 42 ( r 2 = 0.343; P  < 0.001). Alpha peak frequency was not associated with neurodegeneration. Higher CSF neurofilament light was associated with lower total EEG power ( r 2 = 0.136; P  = 0.018), theta power ( r 2 = 0.148; P  = 0.014) and beta power ( r 2 = 0.216; P  = 0.002); the latter was also associated with normalized hippocampal volume ( r 2 = 0.196; P  = 0.002). Amyloid-tau and neurodegenerative pathologies are associated with distinct electrophysiological signatures that may be useful as mechanistic tools and diagnostic/treatment effect biomarkers in clinical trials., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Delirium frequently affects older patients, increasing morbidity and mortality; however, the pathogenesis is poorly understood. Herein, we tested the cognitive disintegration model, which proposes that a breakdown in frontoparietal connectivity, provoked by increased slow-wave activity (SWA), causes delirium., Methods: We recruited 70 surgical patients to have preoperative and postoperative cognitive testing, EEG, blood biomarkers, and preoperative MRI. To provide evidence for causality, any putative mechanism had to differentiate on the diagnosis of delirium; change proportionally to delirium severity; and correlate with a known precipitant for delirium, inflammation. Analyses were adjusted for multiple corrections (MCs) where appropriate., Results: In the preoperative period, subjects who subsequently incurred postoperative delirium had higher alpha power, increased alpha band connectivity (MC P<0.05), but impaired structural connectivity (increased radial diffusivity; MC P<0.05) on diffusion tensor imaging. These connectivity effects were correlated (r 2 =0.491; P=0.0012). Postoperatively, local SWA over frontal cortex was insufficient to cause delirium. Rather, delirium was associated with increased SWA involving occipitoparietal and frontal cortex, with an accompanying breakdown in functional connectivity. Changes in connectivity correlated with SWA (r 2 =0.257; P<0.0001), delirium severity rating (r 2 =0.195; P<0.001), interleukin 10 (r 2 =0.152; P=0.008), and monocyte chemoattractant protein 1 (r 2 =0.253; P<0.001)., Conclusions: Whilst frontal SWA occurs in all postoperative patients, delirium results when SWA progresses to involve posterior brain regions, with an associated reduction in connectivity in most subjects. Modifying SWA and connectivity may offer a novel therapeutic approach for delirium., Clinical Trial Registration: NCT03124303, NCT02926417., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light and that this putative neurotoxicity may contribute to the pathogenesis of delirium itself, independent of changes in inflammation., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Surface modified superparamagnetic iron oxide nanoparticles are assembled into nanostructured micro-raspberry particles via spray drying. The micro-raspberry powder is readily redispersed to individual nanoparticles or nanostructured sub-units, depending on the initially adjusted nanoparticle modification. In this work, it is demonstrated how the technique of magnetic zero-field-cooled/field-cooled (ZFC/FC) measurements can be used to judge the degree of agglomeration, i.e. the extent of hard-agglomerates and soft-agglomerates in a system and predict the redispersibility of the powder particles. Furthermore, the uniformity of surface modification of the individual nanoparticles can be judged via this method. In addition, the technique can be applied to characterise complex nanostructured particle systems composed of iron oxide nanoparticles mixed with another type of nanoparticulate building-block. Thus, this work shows that magnetic measurement techniques are a promising approach to characterise agglomeration states of nanoparticles, their degree of surface modification and their distribution in complex particle and composite systems., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Despite immense progress in nanoscience and technology, one of the yet unsolved challenges is the redispersion of nanoparticles from dry powders back to the individual, primary particles. Herein, an easy to handle powder consisting of nanostructured micron sized raspberry-like particles is presented. These nanostructured micro-raspberries are composed of individual nanoparticles which are equipped with molecules that introduce a separating effect or "spring" functionality. Thereby, a powder system is obtained that allows for an easy and complete redispersibility of the agglomerates down to the level of individual nanoparticles in solvents and polymers. The mechanism of redispersibility involves mechanic stimuli/force as well as solvent like disintegration aspects ("like dissolves like" effect). Furthermore, by tailoring the degree of spacer-equipped particles, the bursting behavior can also be tuned, yielding different redispersion degrees. The redispersibility of the nanostructured micro-raspberries is demonstrated in solvents and silicone-based nanocomposites., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Active silica nanoparticle-based raspberry-like container depots for agents such as antimicrobial substances are presented. The nano raspberry-containers are integrated into coatings in a way that they form a mole-hill structure; i.e., they are partly standing out of the coating. As an application example, it is demonstrated that the containers can be filled with antimicrobially active agents such as nano ZnO or Ag or organic molecules such as thymol. It is demonstrated that the containers can be partly chopped-off via abrasion by rubbing over the surface. This mechanism proves to be an attractive approach to render surfaces refreshable. A first proof of principle for antimicrobial activity of the intact containers in the coatings and the abrasion treated, chopped-off (and thereby reactivated) containers is demonstrated.