OMA1 protease eliminates arrested protein import intermediates upon mitochondrial depolarization.

Most mitochondrial proteins originate from the cytosol and require transport into the organelle. Such precursor proteins must be unfolded to pass through translocation channels in mitochondrial membranes. Misfolding of transported proteins can result in their arrest and translocation failure. Arrested proteins block further import, disturbing mitochondrial functions and cellular proteostasis. Cellular responses to translocation failure have been defined in yeast. We developed the cell line-based translocase clogging model to discover molecular mechanisms that resolve failed import events in humans. The mechanism we uncover differs significantly from these described in fungi, where ATPase-driven extraction of blocked protein is directly coupled with proteasomal processing. We found human cells to rely primarily on mitochondrial factors to clear translocation channel blockage. The mitochondrial membrane depolarization triggered proteolytic cleavage of the stalled protein, which involved mitochondrial protease OMA1. The cleavage allowed releasing the protein fragment that blocked the translocase. The released fragment was further cleared in the cytosol by VCP/p97 and the proteasome.

Covalent-organic framework nanobionics for robust cytoprotection.

We present a novel study introducing a durable and robust covalent-organic framework (COF) nanocoating, developed in situ on living cells. This COF nanocoating demonstrates remarkable resistance against a diverse range of lethal stressors, including high temperature, extreme pH, ultraviolet radiation, toxic metal ions, organic pollutants, and strong oxidative stress. Notably, the nanocoating exhibits exceptional cell survival enhancement under high temperature and strongly acidic conditions, an aspect yet unexplored in the case of metal-organic framework nanocoatings and other nanomaterials. Moreover, functionalization of the nanocoating with an exogenous enzyme catalase enables yeast fermentation and ethanol production even under strong oxidative stress. Our findings establish the durable and robust COF nanocoating as a reliable platform for safeguarding vulnerable microorganisms to allow their utilisation in a wide range of adverse environments.

Oocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors.

Mammalian oocytes develop and mature in a mutually dependent relationship with surrounding cumulus cells. The oocyte actively regulates cumulus cell differentiation and function by secreting soluble paracrine oocyte-secreted factors (OSFs). We characterized the molecular mechanisms by which two model OSFs, cumulin and BMP15, regulate oocyte maturation and cumulus-oocyte cooperativity. Exposure to these OSFs during mouse oocyte maturation in vitro altered the proteomic and multispectral autofluorescence profiles of both the oocyte and cumulus cells. In oocytes, cumulin significantly upregulated proteins involved in nuclear function. In cumulus cells, both OSFs elicited marked upregulation of a variety of metabolic processes (mostly anabolic), including lipid, nucleotide, and carbohydrate metabolism, whereas mitochondrial metabolic processes were downregulated. The mitochondrial changes were validated by functional assays confirming altered mitochondrial morphology, respiration, and content while maintaining ATP homeostasis. Collectively, these data demonstrate that cumulin and BMP15 remodel cumulus cell metabolism, instructing them to upregulate their anabolic metabolic processes, while routine cellular functions are minimized in the oocyte during maturation, in preparation for ensuing embryonic development.NEW & NOTEWORTHY Oocyte-secreted factors (OSFs) promote oocyte and cumulus cell cooperativity by altering the molecular composition of both cell types. OSFs downregulate protein catabolic processes and upregulate processes associated with DNA binding, translation, and ribosome assembly in oocytes. In cumulus cells, OSFs alter mitochondrial number, morphology, and function, and enhance metabolic plasticity by upregulating anabolic pathways. Hence, the oocyte via OSFs, instructs cumulus cells to increase metabolic processes on its behalf, thereby subduing oocyte metabolism.

ROS-mediated anticancer effects of EGFR-targeted nanoceria.

The therapeutic effectiveness of anticancer drugs, including nanomedicines, can be enhanced with active receptor-targeting strategies. Epidermal growth factor receptor (EGFR) is an important cancer biomarker, constitutively expressed in sarcoma patients of different histological types. The present work reports materials and in vitro biomedical analyses of silanized (passive delivery) and/or EGF-functionalized (active delivery) ceria nanorods exhibiting highly defective catalytically active surfaces. The EGFR-targeting efficiency of nanoceria was confirmed by receptor-binding studies. Increased cytotoxicity and reactive oxygen species (ROS) production were observed for EGF-functionalized nanoceria owing to enhanced cellular uptake by HT-1080 fibrosarcoma cells. The uptake was confirmed by TEM and confocal microscopy. Silanized nanoceria demonstrated negligible/minimal cytotoxicity toward healthy MRC-5 cells at 24 and 48 h, whereas this was significant at 72 h owing to a nanoceria accumulation effect. In contrast, considerable cytotoxicity toward the cancer cells was exhibited at all three times points. The ROS generation and associated cytotoxicity were moderated by the equilibrium between catalysis by ceria, generation of cell debris, and blockage of active sites. EGFR-targeting is shown to enhance the uptake levels of nanoceria by cancer cells, subsequently enhancing the overall anticancer activity and therapeutic performance of ceria.

UiO-66-NH2 Metal-Organic Framework for the Detection of Alzheimer's Biomarker Aß (1-42).

Neurodegenerative disorders pose a significant challenge to global healthcare, with Alzheimer's disease (AD) being one of the most prevalent forms. Early and accurate detection of amyloid-ß (Aß) (1-42) monomers, a key biomarker of AD pathology, is crucial for effective diagnosis and intervention of the disease. Current gold standard detection techniques for Aß include enzyme-linked immunosorbent assay and surface plasmon resonance. Although reliable, they are limited by their cost and time-consuming nature, thus restricting their point-of-care applicability. Here we present a sensitive and rapid colorimetric sensor for the detection of Aß (1-42) monomers within 5 min. This was achieved by harnessing the peroxidase-like activity of metal-loaded metal-organic frameworks (MOFs), specifically UiO-66-NH2, coupled with the strong affinity of Aß (1-42) to the MOFs. Various metal-loaded MOFs were synthesized and investigated, and platinum-loaded UiO-66-NH2 was identified as the optimal candidate for our purpose. The Pt-loaded UiO-66-NH2 sensor demonstrated detection limits of 2.76 and 4.65 nM Aß (1-42) monomers in water and cerebrospinal fluid, respectively, with a linear range from 0.75 to 25 nM (R2 = 0.9712), outperforming traditional detection techniques in terms of both detection time and complexity. Moreover, the assay was specific toward Aß (1-42) monomers when evaluated against interfering compounds. The rapid and cost-effective sensor may help circumvent the limitations of conventional detection methods, thus providing a promising avenue for early AD diagnosis and facilitating improved clinical outcomes.

Molecular dissection of the soluble photosynthetic antenna from the cryptophyte alga Hemiselmis andersenii.

Cryptophyte algae have a unique phycobiliprotein light-harvesting antenna that fills a spectral gap in chlorophyll absorption from photosystems. However, it is unclear how the antenna transfers energy efficiently to these photosystems. We show that the cryptophyte Hemiselmis andersenii expresses an energetically complex antenna comprising three distinct spectrotypes of phycobiliprotein, each composed of two αß protomers but with different quaternary structures arising from a diverse α subunit family. We report crystal structures of the major phycobiliprotein from each spectrotype. Two-thirds of the antenna consists of open quaternary form phycobiliproteins acting as primary photon acceptors. These are supplemented by a newly discovered open-braced form (~15%), where an insertion in the α subunit produces ~10 nm absorbance red-shift. The final components (~15%) are closed forms with a long wavelength spectral feature due to substitution of a single chromophore. This chromophore is present on only one ß subunit where asymmetry is dictated by the corresponding α subunit. This chromophore creates spectral overlap with chlorophyll, thus bridging the energetic gap between the phycobiliprotein antenna and the photosystems. We propose that the macromolecular organization of the cryptophyte antenna consists of bulk open and open-braced forms that transfer excitations to photosystems via this bridging closed form phycobiliprotein.

Emerging Aeromonas enteric infections: their association with inflammatory bowel disease and novel pathogenic mechanisms.

Aeromonas species are emerging human enteric pathogens. This study examines the isolation of Aeromonas and other enteric bacterial pathogens from patients with and without inflammatory bowel disease (IBD). This study also investigates the intestinal epithelial pathogenic mechanisms of Aeromonas veronii. The isolation rates of seven enteric bacterial pathogens from 2,279 patients with IBD and 373,276 non-IBD patients were compared. An A. veronii strain (AS1) isolated from intestinal biopsies of a patient with IBD was used for pathogenic mechanism investigation, and Escherichia coli K12 was used as a bacterial control. HT-29 cells were used as a model of human intestinal epithelium. A significantly higher isolation of Aeromonas species was found in patients with IBD as compared to non-IBD patients (P = 0.0001, odds ratio = 2.11). A. veronii upregulated 177 inflammatory genes and downregulated 52 protein-coding genes affecting chromatin assembly, multiple small nuclear RNAs, multiple nucleolar RNAs, and 55 cytoplasmic tRNAs in HT-29 cells. These downregulation effects were unique to A. veronii and not observed in HT-29 cells infected with E. coli K12. A. veronii induced intestinal epithelial apoptosis involving the intrinsic pathway. A. veronii caused epithelial microvilli shortening and damage and epithelial production of IL-8. In conclusion, this study for the first time reports the association between IBD and Aeromonas enteric infection detected by bacterial cultivation. This study also reports that A. veronii damages intestinal epithelial cells via multiple mechanisms, of which the downregulating cytoplasmic tRNA, small nuclear RNA, and small nucleolar RNA are novel bacterial pathogenic mechanisms. IMPORTANCE This study for the first time reports the association between inflammatory bowel disease (IBD) and Aeromonas enteric infection detected by bacterial pathogen cultivation, highlighting the need of clinical and public health attention. The finding that patients with IBD are more susceptible to Aeromonas enteric infection suggests that detection of Aeromonas enteric infection should be routinely performed for the diagnosis and treatment of IBD. This study also reports novel bacterial pathogenic mechanisms employed by Aeromonas veronii. Through comparative transcriptomic analysis and other techniques, this study revealed the pathogenic mechanisms by which A. veronii causes damage to intestinal epithelial cells. Among the various pathogenic mechanisms identified, the downregulating tRNA, small nuclear and nucleolar RNAs in human intestinal epithelial cells are novel bacterial pathogenic mechanisms.

Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer's Disease.

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer's disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (Aß) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-Aß antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle's binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI.

A liquid metal-polydopamine composite for cell culture and electro-stimulation.

Gallium (Ga) is a low melting point metal in the liquid state in the biological environment which presents a unique combination of fluidity, softness, and metallic electrical and thermal properties. In this work, liquid Ga is proposed as a biocompatible electrode material for cell culture by electro-stimulation since the cytotoxicity of Ga is generally considered low and some Ga compounds have been reported to exhibit anti-bacterial and anti-inflammatory activities. Complementarily, polydopamine (PDA) was coated on liquid Ga to increase the attachment capability of cells on the liquid Ga electrode and provide enhanced biocompatibility. The liquid Ga layer could be readily painted at room temperature on a solid inert substrate, followed by the formation of a nanoscale PDA coating layer resulting in a conformable and biocompatible composite electrode. The PDA layer was shown to coordinate with Ga3+, which is sourced from liquid Ga, providing electrical conductivity in the cell culture medium. The PDA-Ga3+ composite acted as a conductive substrate for advanced electro-stimulation for cell culture methods of representative animal fibroblasts. The cell proliferation was observed to increase by ∼143% as compared to a standard glass coverslip at a low potential of 0.1 V of direct coupling stimulation. This novel PDA-Ga3+ composite has potential applications in cell culture and regenerative medicine.

Electron Microscopy and Elemental Analysis of Defective Drysdale Nucleus Manipulator Instruments Implicated in Surgical Complications.

PURPOSE: To analyze microtopography of 5 reusable Drysdale nucleus manipulator (DNM) paddled tips for sharp defects and evaluate their elemental composition to determine probable source, investigating 2 instruments (DNM 1 and 4) implicated in causing posterior capsule rupture (PCR) and 3 instruments with sharp edges identified by finger-tip interrogation intraoperatively. DESIGN: Experimental laboratory investigation. METHODS: DNM paddled tips were analyzed using scanning electron microscopy (SEM) to evaluate for sharp surface defects (number, dimensions), and subsequently energy dispersive x-ray spectroscopy (EDS) performed on sharp defects to determine their elemental composition. RESULTS: All reused DNMs analyzed (5 of 5) had significant structural defects on SEM analysis including sharp burrs, cavities and indentations, surface debris or residues, and roughening, compared to the new instrument (DNM 3, control) which had no defects. DNM 1 had 2 sharp defects, a larger 14 × 76-µm one and a craterlike 167 × 220-µm defect containing debris. EDS found that DNM 2 had 3 of 4 burrs composed mainly of carbon, the fourth of mixed composition (calcium, sulfur, oxygen); DNM 4 had 1 small burr, EDS significant for carbon; DNM 5 had 3 prominent burrs, the largest of 20 × 28 µm, 2 composed of aluminum, and some carbon residue. DNM 6 had 1 burr composed of aluminum and 3 prominent cavity defects, the largest covering 781 µm2. CONCLUSION: Reusable DNMs are widely used in cataract surgery. Sharp carbon- or aluminum-containing burrs were detected on all reused instruments analyzed together with 1 burr of mixed composition, originating from (1) organic residues, (2) instrument fragments, or (3) salt and contaminant deposits. Sharp defects may contribute to capsular damage including PCR, and residues may pose other safety concerns. Therefore, we support development of a quality, reliable single-use alternative instrument and further encourage careful inspection of all reusable instruments principally by finger-tip interrogation for sharp edges preuse.

Mechanistic Observation of Interactions between Macrophages and Inorganic Particles with Different Densities.

Many different types of inorganic materials are processed into nano/microparticles for medical utilization. The impact of selected key characteristics of these particles, including size, shape, and surface chemistries, on biological systems, is frequently studied in clinical contexts. However, one of the most important basic characteristics of these particles, their density, is yet to be investigated. When the particles are designed for drug delivery, highly mobile macrophages are the major participants in cellular levels that process them in vivo. As such, it is essential to understand the impact of particles' densities on the mobility of macrophages. Here, inorganic particles with different densities are applied, and their interactions with macrophages studied. A set of these particles are incubated with the macrophages and the outcomes are explored by optical microscopy. This microscopic view provides the understanding of the mechanistic interactions between particles of different densities and macrophages to conclude that the particles' density can affect the migratory behaviors of macrophages: the higher the density of particles engulfed inside the macrophages, the less mobile the macrophages become. This work is a strong reminder that the density of particles cannot be neglected when they are designed to be utilized in biological applications.

Macrophage-Targeting and Complete Lysosomal Degradation of Self-assembled Two-Dimensional Poly(ε-caprolactone) Platelet Particles.

Understanding cellular uptake and particle trafficking within the cells is essential for targeted drug delivery applications. Existing studies reveal that the geometrical aspects of nanocarriers, for example, shape and size, determine their cell uptake and sub-cellular transport pathways. However, considerable efforts have been directed toward understanding the cell uptake mechanism and trafficking of spherical particles. Detailed analysis on the uptake mechanism and downstream intracellular processing of non-spherical particles remains elusive. Here, we used polymeric two-dimensional platelets based on poly(ε-caprolactone) (PCL) prepared by living crystallization-driven self-assembly as a platform to investigate the cell uptake and intracellular transport of non-spherical particles in vitro. PCL is known to degrade only slowly, and these platelets were still stable after 2 days of incubation in artificial lysosomal media. Upon cell uptake, the platelets were transported through an endo/lysosomal pathway and were found to degrade completely in the lysosome at the end of the cell uptake cycle. We observed a morphological transformation of the lysosomes, which correlates with the stages of platelet degradation in the lysosome. Overall, we found an accelerated degradation of PCL, which was likely caused by mechanical forces inside the highly stretched endosomes.

RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3'UTR required for intermediate vancomycin resistance.

Treatment of methicillin-resistant Staphylococcus aureus infections is dependent on the efficacy of last-line antibiotics including vancomycin. Treatment failure is commonly linked to isolates with intermediate vancomycin resistance (termed VISA). These isolates have accumulated point mutations that collectively reduce vancomycin sensitivity, often by thickening the cell wall. Changes in regulatory small RNA expression have been correlated with antibiotic stress in VISA isolates however the functions of most RNA regulators is unknown. Here we capture RNA-RNA interactions associated with RNase III using CLASH. RNase III-CLASH uncovers hundreds of novel RNA-RNA interactions in vivo allowing functional characterisation of many sRNAs for the first time. Surprisingly, many mRNA-mRNA interactions are recovered and we find that an mRNA encoding a long 3' untranslated region (UTR) (termed vigR 3'UTR) functions as a regulatory 'hub' within the RNA-RNA interaction network. We demonstrate that the vigR 3'UTR promotes expression of folD and the cell wall lytic transglycosylase isaA through direct mRNA-mRNA base-pairing. Deletion of the vigR 3'UTR re-sensitised VISA to glycopeptide treatment and both isaA and vigR 3'UTR deletions impact cell wall thickness. Our results demonstrate the utility of RNase III-CLASH and indicate that S. aureus uses mRNA-mRNA interactions to co-ordinate gene expression more widely than previously appreciated.

Gallium Nanodroplets are Anti-Inflammatory without Interfering with Iron Homeostasis.

Gallium (Ga) compounds, as the source of Ga ions (Ga3+), have been historically used as anti-inflammatories. Currently, the widely accepted mechanisms of the anti-inflammatory effects for Ga3+ are rationalized on the basis of their similarities to ferric ions (Fe3+), which permits Ga3+ to bind with Fe-binding proteins and subsequently disturbs the Fe homeostasis in the immune cells. Here in contrast to the classic views, our study presents the mechanisms of Ga as anti-inflammatory by delivering Ga nanodroplets (GNDs) into lipopolysaccharide-induced macrophages and exploring the processes. The GNDs show a selective inhibition of nitric oxide (NO) production without affecting the accumulation of pro-inflammatory mediators. This is explained by GNDs disrupting the synthesis of inducible NO synthase in the activated macrophages by upregulating the levels of eIF2α phosphorylation, without interfering with the Fe homeostasis. The Fe3+ transferrin receptor-independent endocytosis of GNDs by the cells prompts a fundamentally different mechanism as anti-inflammatories in comparison to that imparted by Ga3+. This study reveals the fundamental molecular basis of GND-macrophage interactions, which may provide additional avenues for the use of Ga for anti-inflammatory and future biomedical and pharmaceutical applications.

Nanocellulose from Nata de Coco as a Bioscaffold for Cell-Based Meat.

The three-dimensional formation of bio-engineered tissue for applications such as cell-based meat requires critical interaction between the bioscaffold and cellular biomass. To explore the features underlying this interaction, we have assessed the commercially available bacterial nanocellulose (BNC) product from Cass Materials for its suitability to serve as a bioscaffold for murine myoblast attachment, proliferation, and differentiation. Rigorous application of both scanning electron microscopy and transmission electron microscopy reveals cellular details of this interaction. While the retention rate of myoblast cells appears low, BNC is able to provide effective surface parameters for the formation of anchor points to form mature myotubes. Understanding the principles that govern this interaction is important for the successful scaling of these materials into edible, commercially viable, and nutritious biomass.

Influence of Anionic Surfactants on the Fundamental Properties of Polymer/Reduced Graphene Oxide Nanocomposite Films.

Surfactants are frequently employed in the fabrication of polymer/graphene-based nanocomposites via emulsion techniques. However, the impact of surfactants on the electrical and mechanical properties of such nanocomposite films remains to be explored. We have systematically studied the impact of two anionic surfactants [sodium dodecyl sulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS)] on intrinsic properties of the nanocomposite films comprising reduced graphene oxide in a matrix of poly(styrene-stat-n-butyl acrylate). Using these ambient temperature film-forming systems, we fabricated films with different concentrations of the surfactants (1-7 wt %, relative to the organic phase). Significant differences in film properties were observed both as a function of amount and type of surfactant. Thermally reduced films exhibited concentration-dependent increases in surface roughness, electrical conductivity, and mechanical properties with increasing SDS content. When compared with SDBS, SDS films exhibited an order of magnitude higher electrical conductivity values at every concentration (highest value of ∼4.4 S m-1 for 7 wt % SDS) and superior mechanical properties at higher surfactant concentrations. The present results illustrate how the simple inclusion of a benzene ring in the SDS structure (as in SDBS) can cause a significant change in the electrical and mechanical properties of the nanocomposite. Overall, the present results demonstrate how nanocomposite properties can be judiciously manipulated by altering the concentration and/or type of surfactant.

Characterization of a novel roseophage and the morphological and transcriptional response of the sponge symbiont Ruegeria AU67 to infection.

Sponges have recently been recognized to contain complex communities of bacteriophages; however, little is known about how they interact with their bacterial hosts. Here, we isolated a novel phage, called Ruegeria phage Tedan, and characterized its impact on the bacterial sponge symbiont Ruegeria AU67 on a morphological and molecular level. Phage Tedan was structurally, genomically and phylogenetically characterized to be affiliated with the genus Xiamenvirus of the family Siphoviridae. Through microscopic observations and transcriptomic analysis, we show that phage Tedan upon infection induces a process leading to metabolic and morphological changes in its host. These changes would render Ruegeria AU67 better adapted to inhabit the sponge holobiont due to an improved utilization of ecologically relevant energy and carbon sources as well as a potential impediment of phagocytosis by the sponge through cellular enlargement. An increased survival or better growth of the bacterium in the sponge environment will likely benefit the phage reproduction. Our results point towards the possibility that phages from host-associated environments require, and have thus evolved, different strategies to interact with their host when compared to those phages from free-living or planktonic environments.

ß-Glucan from Lentinula edodes prevents cognitive impairments in high-fat diet-induced obese mice: involvement of colon-brain axis.

BACKGROUND: Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-ß-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes (L. edodes), has the potential to remodel gut microbiota. However, the effects of L. edodes derived ß-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes ß-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet. METHODS: C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edodes ß-glucan supplementation diets for 7 days (short-term) or 15 weeks (long-term). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS: We reported that short-term and long-term L. edodes ß-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Long-term L. edodes ß-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the ß-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the ß-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. CONCLUSIONS: This study revealed that L. edodes ß-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes ß-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.

Effect of a protein corona on the fibrinogen induced cellular oxidative stress of gold nanoparticles.

The protein corona of nanoparticles is becoming a tool to understand the relation between intrinsic physicochemical properties and extrinsic biological behaviour. A diverse set of characterisation techniques such as transmission electron microscopy, mass spectrometry, dynamic light scattering, zeta-potential measurements and surface enhanced Raman spectroscopy are used to determine the composition and physical properties of the soft and hard corona formed around spherical gold nanoparticles. Advanced characterisation via small angle X-ray scattering and cryo-transmission electron microscopy suggests the presence of a thin hard corona of a few nm on 50 nm gold nanoparticles. The protein corona does not cause changes in cell viability, but inhibits the generation of reactive oxygen species in microglia cells. When a pre-incubated layer of fibrinogen, a protein with high affinity for the gold surface, is present around the nanoparticles before a protein corona is formed in bovine serum, the cellular uptake is significantly increased with an inhibition of ROS. The selective sequential pre-formation of protein complexes prior to incubation in cells is demonstrated as a viable method to alter the biological behaviour of nanoparticles.