Discovery and Optimization of Neutralizing SARS-CoV-2 Antibodies Using ALTHEA Gold Plus Libraries™.

We recently reported the isolation and characterization of anti-SARS-CoV-2 antibodies from a phage display library built with the VH repertoire of a convalescent COVID-19 patient, paired with four naïve synthetic VL libraries. One of the antibodies, called IgG-A7, neutralized the Wuhan, Delta (B.1.617.2) and Omicron (B.1.1.529) strains in authentic neutralization tests (PRNT). It also protected 100% transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from SARS-CoV-2 infection. In this study, the four synthetic VL libraries were combined with the semi-synthetic VH repertoire of ALTHEA Gold Libraries™ to generate a set of fully naïve, general-purpose, libraries called ALTHEA Gold Plus Libraries™. Three out of 24 specific clones for the RBD isolated from the libraries, with affinity in the low nanomolar range and sub-optimal in vitro neutralization in PRNT, were affinity optimized via a method called "Rapid Affinity Maturation" (RAM). The final molecules reached sub-nanomolar neutralization potency, slightly superior to IgG-A7, while the developability profile over the parental molecules was improved. These results demonstrate that general-purpose libraries are a valuable source of potent neutralizing antibodies. Importantly, since general-purpose libraries are "ready-to-use", it could expedite isolation of antibodies for rapidly evolving viruses such as SARS-CoV-2.

Redox-Mediated Gold Nanoparticles with Glucose Oxidase and Egg White Proteins for Printed Biosensors and Biofuel Cells.

Glucose oxidase (GOx)-based electrodes are important for bioelectronics, such as glucose sensors. It is challenging to effectively link GOx with nanomaterial-modified electrodes while preserving enzyme activity in a biocompatible environment. To date, no reports have used biocompatible food-based materials, such as egg white proteins, combined with GOx, redox molecules, and nanoparticles to create the biorecognition layer for biosensors and biofuel cells. This article demonstrates the interface of GOx integrated with egg white proteins on a 5 nm gold nanoparticle (AuNP) functionalized with a 1,4-naphthoquinone (NQ) and conjugated with a screen-printed flexible conductive carbon nanotube (CNT)-modified electrode. Egg white proteins containing ovalbumin can form three-dimensional scaffolds to accommodate immobilized enzymes and adjust the analytical performance. The structure of this biointerface prevents the escape of enzymes and provides a suitable microenvironment for the effective reaction. The bioelectrode's performance and kinetics were evaluated. Using redox-mediated molecules with the AuNPs and the three-dimensional matrix made of egg white proteins improves the transfer of electrons between the electrode and the redox center. By engineering the layer of egg white proteins on the GOx-NQ-AuNPs-mediated CNT-functionalized electrodes, we can modulate analytical performances such as sensitivity and linear range. The bioelectrodes demonstrate high sensitivity and can prolong the stability by more than 85% after 6 h of continuous operation. The use of food-based proteins with redox molecule-modified AuNPs and printed electrodes demonstrates advantages for biosensors and energy devices due to their small size, large surface area, and ease of modification. This concept holds a promise for creating biocompatible electrodes for biosensors and self-sustaining energy devices.

Determining the impact of gold nanoparticles on amyloid aggregation with 2D IR spectroscopy.

As nanomaterials become more prevalent in both industry and medicine, it is crucial to fully understand their health risks. One area of concern is the interaction of nanoparticles with proteins, including their ability to modulate the uncontrolled aggregation of amyloid proteins associated with diseases, such as Alzheimer's disease and type II diabetes, and potentially extend the lifetime of cytotoxic soluble oligomers. This work demonstrates that two-dimensional infrared spectroscopy and 13C18O isotope labeling can be used to follow the aggregation of human islet amyloid polypeptide (hIAPP) in the presence of gold nanoparticles (AuNPs) with single-residue structural resolution. 60 nm AuNPs were found to inhibit hIAPP, tripling the aggregation time. Furthermore, calculating the actual transition dipole strength of the backbone amide I' mode reveals that hIAPP forms a more ordered aggregate structure in the presence of AuNPs. Ultimately, such studies can provide insight into how mechanisms of amyloid aggregation are altered in the presence of nanoparticles, furthering our understanding of protein-nanoparticle interactions.

Effects of synchrotron-based X-rays and gold nanoparticles on normal and cancer cell morphology and migration.

It has been shown lately that gold nanoparticles (AuNPs) and ionizing radiation (IR) have inhibitory effects on cancer cell migration while having promoting effects on normal cells' motility. Also, IR increases cancer cell adhesion with no significant effects on normal cells. In this study, synchrotron-based microbeam radiation therapy, as a novel pre-clinical radiotherapy protocol, is employed to investigate the effects of AuNPs on cell migration. Experiments were conducted utilizing synchrotron X-rays to investigate cancer and normal cell morphology and migration behaviour when they are exposed to synchrotron broad beams (SBB) and synchrotron microbeams (SMB). This in vitro study was conducted in two phases. In phase I two cancer cell lines - human prostate (DU145) and human lung (A549) - were exposed to various doses of SBB and SMB. Based on the phase I results, in phase II two normal cell lines were studied: human epidermal melanocytes (HEM) and human primary colon epithelial (CCD841), along with their respective cancerous counterparts, human primary melanoma (MM418-C1) and human colorectal adenocarcinoma (SW48). The results show that radiation-induced damage in cells' morphology becomes visible with SBB at doses greater than 50 Gy, and incorporating AuNPs increases this effect. Interestly, under the same conditions, no visible morphological changes were observed in the normal cell lines post-irradiation (HEM and CCD841). This can be attributed to the differences in cell metabolic and reactive oxygen species levels between normal and cancer cells. The outcome of this study highlights future applications of synchrotron-based radiotherapy, where it is possible to deliver extremely high doses to cancer tissues whilst preserving surrounding normal tissues from radiation-induced damage.

An ultrasensitive split-type electrochemical immunosensor based on controlled-release strategy for detection of CA19-9.

In this study, a novel split-type electrochemical immunosensor based on controlled release strategy was proposed for sensitive analysis and detection of tumor marker carbohydrate antigen 199 (CA19-9). Specifically, glucose (Glu) was encapsulated in carrier mesoporous silica (MSN) with encapsulation technology, and surface functionalized Zinc sulfide (ZnS) caps were used as "gatekeepers". The complex is formed by encapsulating Glu within MSN with ZnS (ZnS@MSN-Glu) as a signal amplifier labeled on the signal antibody (Ab2). And the Ab2 can detect the presence of antibodies. To reduce the interference of biological analysis, the immune recognition process of ZnS@MSN-Glu-Ab2 bioconjugate and antigen was carried out in 96-well microplate, which did not interfere with the electrochemical analysis process. Therefore, the low sensitivity detection caused by biofouling of nanomaterials and immunoreaction on the testing platform is eliminated. Subsequently, the opening and timed release of mesopores were controlled by external stimuli, the disulfide bond cleavage by dithiothreitol (DTT), and glucose was effectively released. Then nickel cobalt layered double hydroxide (NiCo-LDH) were directly hydrothermally grown on carbon cloth (CC) electrodeposited with copper selenide (CuSe) nanosheets to construct three-dimensional (3D) cactus-like NiCo-LDH/CuSe/CC sensing platform. It can realize the catalytic oxidation of released glucose, triggering glucose-mediated signal amplification. The synergistic effect of the 3D cactus structure and active nanomaterials promotes electron conduction. Taking the detection of carbohydrate antigen CA19-9 as an example, the immunosensor shows a wide linear concentration range (0.001-100 U/mL) with the limit of detection of 0.0005 U/mL, realizing highly sensitive detection of CA19-9. This biosensing technique has considerable advantages and provides an innovative approach for trace detection of other biomarkers.

Dual-ratiometric aptasensor for simultaneous detection of malathion and profenofos based on hairpin tetrahedral DNA nanostructures.

Due to the diversification and complexity of organophosphorus pesticide residues brings great challenges to the detection work. Therefore, we developed a dual-ratiometric electrochemical aptasensor that could detect malathion (MAL) and profenofos (PRO) simultaneously. In this study, metal ions, hairpin-tetrahedral DNA nanostructures (HP-TDN) and nanocomposites were used as signal tracers, sensing framework and signal amplification strategy respectively to develop the aptasensor. Thionine (Thi) labeled HP-TDN (HP-TDNThi) provided specific binding sites for assembling Pb2+ labeled MAL aptamer (Pb2+-APT1) and Cd2+ labeled PRO aptamer (Cd2+-APT2). When the target pesticides were present, Pb2+-APT1 and Cd2+-APT2 were dissociated from the hairpin complementary strand of HP-TDNThi, resulting in reduced oxidation currents of Pb2+ (IPb2+) and Cd2+ (ICd2+), respectively, while the oxidation currents of Thi (IThi) remained unchanged. Thus, IPb2+/IThi and ICd2+/IThi oxidation current ratios were used to quantify MAL and PRO, respectively. In addition, the gold nanoparticles (AuNPs) encapsulated in the zeolitic imidazolate framework (ZIF-8) nanocomposites (Au@ZIF-8) greatly increased the catch of HP-TDN, thereby amplifying the detection signal. The rigid three-dimensional structure of HP-TDN could reduce the steric hindrance effect on the electrode surface, which could greatly improve the recognition efficiency of the aptasensor for the pesticide. Under the optimal conditions, the detection limits of the HP-TDN aptasensor for MAL and PRO were 4.3 pg mL-1 and 13.3 pg mL-1, respectively. Our work proposed a new approach to fabricating a high-performance aptasensor for simultaneous detection of multiple organophosphorus pesticides, opening a new avenue for the development of simultaneous detection sensors in the field of food safety and environmental monitoring.

nanoGold and µGold inhibit autoimmune inflammation: a review.

The newest data on metallic gold have placed the noble metal central in the fight for the safe treatment of autoimmune inflammation. There are two different ways to use gold for the treatment of inflammation: gold microparticles > 20 µm and gold nanoparticles. The injection of gold microparticles (µGold) is a purely local therapy. µGold particles stay put where injected, and gold ions released from them are relatively few and taken up by cells within a sphere of only a few millimeters in diameter from their origin particles. The macrophage-induced release of gold ions may continue for years. Injection of gold nanoparticles (nanoGold), on the other hand, is spread throughout the whole body, and the bio-released gold ions, therefore, affect multitudes of cells all over the body, as when using gold-containing drugs such as Myocrisin. Since macrophages and other phagocytotic cells take up and transport nanoGold and remove it after a short period, repeated treatment is necessary. This review describes the details of the cellular mechanisms that lead to the bio-release of gold ions in µGold and nanoGold.

Gold@Carbon Quantum Dots Nanocomposites Based Two-In-One Sensor: A Novel Approach for Sensitive Detection of Aminoglycosides Antibiotics in Food Samples.

Antibiotics are life-saving drugs for humans, but their unwanted use leads to antibacterial resistance (ABR) and causes serious health problems. The excess of these antibiotics entered to the food chain and caused food contamination. Here, Au@CQDs nanocomposites (NCs) was used as a two-in-one sensor to detect two antibiotics. The color change of AuNCs and fluorescence resonance energy transfer are two distance-dependent phenomena used as sensing mechanisms. In the sensing process, Au@CQDs NCs change their color, enhancing the fluorescence intensity of NCs in the presence of Gentamicin (GENTA) and Kanamycin (KMC) antibiotics. The limit of detection of 116 nM and 133 nM for GENTA and 195 nM and 120 nM for KMC have been achieved with colorimetric and fluorimetric readout, respectively. The practicality of the reported sensor was evaluated in real spiked samples and showed excellent recovery efficiency. Therefore this two-in-one sensor can be used for the food monitoring system.

A clinically feasible diagnostic spectro-histology built on SERS-nanotags for multiplex detection and grading of breast cancer biomarkers.

Simultaneous detection of multiple biomarkers is always an obstacle in immunohistochemical (IHC) analysis. Herein, a straightforward spectroscopy-driven histopathologic approach has emerged as a paradigm of Raman-label (RL) nanoparticle probes for multiplex recognition of pertinent biomarkers in heterogeneous breast cancer. The nanoprobes are constructed by sequential incorporation of signature RL and target specific antibodies on gold nanoparticles, which are coined as Raman-Label surface enhanced Raman scattering (RL-SERS)-nanotags to evaluate simultaneous recognition of clinically relevant breast cancer biomarkers i.e., estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor2 (HER2). As a foot-step assessment, breast cancer cell lines having varied expression levels of the triple biomarkers are investigated. Subsequently, the optimized detection strategy using RL-SERS-nanotags is subjected to clinically confirmed, retrospective formalin-fixed paraffin embedded (FFPE) breast cancer tissue samples to fish out the quick response of singleplex, duplex as well as triplex biomarkers in a single tissue specimen by adopting a ratiometric signature RL-SERS analysis which enabled to minimize the false negative and positive results. Significantly, sensitivity and specificity of 95% and 92% for singleplex, 88% and 85% for duplex, and 75% and 67% for triplex biomarker has been achieved by assessing specific Raman fingerprints of the respective SERS-tags. Furthermore, a semi-quantitative evaluation of HER2 grading between 4+/2+/1+ tissue samples was also achieved by the Raman intensity profiling of the SERS-tag, which is fully in agreement with the expensive fluorescent in situ hybridization analysis. Additionally, the practical diagnostic applicability of RL-SERS-tags has been achieved by large area SERS imaging of areas covering 0.5-5 mm2 within 45 min. These findings unveil an accurate, inexpensive and multiplex diagnostic modality envisaging large-scale multi-centric clinical validation.

Influence of temperature on the torsional properties of two thermally treated NiTi rotary instruments.

This study aimed to evaluate the influence of temperature on torsional strength and angular deflection of two experimental NiTi rotary instruments manufactured from Blue and Gold thermal treatments and with identical cross-sections. A total of 40 experimental NiTi instruments 25.06 and with a triangular cross-section and manufactured from Blue and Gold thermal treatments were used (n=20). The torsional test was performed in the 3 mm from the tip of the instrument according to ISO 3630-1. The torsional test evaluated the torsional strength and angular deflection to failure at room temperature (21°C ± 1° C) and body temperature (36°C ±1°C). The fractured surface of each fragment was observed by using scanning electron microscopy (SEM). Data were analyzed using an unpaired t test for inter and intra-group comparison and the level of significance was set at 5%. The results showed that the body temperature did not affect the torsional strength and angular deflection of the instruments when compared with room temperature (P>0.05). However, at body temperature, the Blue NiTi instruments presented significantly lower angular deflection in comparison with Gold NiTi instruments (P<0.05). There was no significant difference regarding the torsional strength of the instruments at body temperature (P>0.05). The temperature did not affect the torsional strength of the instruments manufactured from Blue and Gold technology. However, the Blue NiTi instruments presented significantly lower angular deflection than Gold instruments at 36°C temperature.

Bacteriophage-based nano-biosensors for the fast impedimetric determination of pathogens in food samples.

The early and rapid detection of pathogenic microorganisms is of critical importance in addressing serious public health issues. Here, a new bacteriophage-based nano-biosensor was constructed and the electrochemical impedimetric method was fully optimized and applied for the quantitative detection of Escherichia coli O157:H7 in food samples. The impact of using a nanocomposite consisting of gold nanoparticles (AuNPs), multi-walled carbon nanotubes (MWCNTs), and tungsten oxide nanostructures (WO3) on the electrochemical performance of disposable screen printed electrodes was identified using the cyclic voltammetry and electrochemical impedance spectroscopy. The use nanomaterials enabled high capturing sensitivity against the targeting bacterial host cells with the limit of detection of 3.0 CFU/ml. Moreover, selectivity of the covalently immobilized active phage was tested against several non-targeting bacterial strains, where a high specificity was achieved. Thus, the targeting foodborne pathogen was successfully detected in food samples with high specificity, and the sensor provided an excellent recovery rate ranging from 90.0 to 108%. Accordingly, the newly developed phage-biosensor is recommended as a disposable label-free impedimetric biosensor for the quick and real-time monitoring of food quality.

MXene supported biomimetic bilayer lipid membrane biosensor for zeptomole detection of BRCA1 gene.

A biomimetic bilayer lipid membrane supported MXene based biosensor is reported for electrochemical hybridization detection of the most prevalent and potential BC biomarker BRCA1. 2D MXene nanosheet-anchored gold nanoparticle-decorated biomimetic bilayer lipid membrane (AuNP@BLM) biosensor is used for the attachment of thiolated single-stranded DNA (HS-ssDNA) targeting hybridization detection. The interaction of biomimetic bilayer lipid membrane with 2D MXene nanosheets is explored in this work for the first time. The synergistic combination of MXene and AuNP@BLM has proven to efficiently improve the detection signal to several folds. The sensor provides hybridization signals only to the complementary DNA (cDNA) sequence with a linearity range 10 zM to 1 µM and LOD of 1 zM without the need of any further amplification. The specificity of the biosensor is validated using non-complementary (ncDNA) and double base mis-match oligonucleotide DNA (dmmDNA) sequences. The sensor successfully distinguishes the signal for different target DNAs with good reproducibility indicated by the RSD value of 4.9%. Hence, we envision that the reported biosensor can be used to construct efficient diagnostic point-of-care tools based on molecular affinity interactions.

Electrocatalytic Activities of a Platinum Nanostructured Electrode Modified by Gold Adatom toward Methanol and Glycerol Electrooxidation in Acid and Alkaline Media.

For practical applications such as fuel cells, it is important to exploit electrocatalysis with high activity for methanol and glycerol oxidation. A platinum nanostructured electrode (PtNPs) is modified by gold adatoms and is created by application of a square wave potential regime to a tantalum surface electrode. In nanostructured platinum, the structure and the surface properties are characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and cyclic voltammetry (CV). In acid and alkaline media, the CV and Chronoamperometric (CA) are studied to investigate the catalytic activity of the PtNPs nanoparticles for the electrooxidation of methanol and glycerol. The prepared nanostructured platinum on a tantalum electrode was allowed to balance an open circuit with a 1.0×10-3 M solution containing an Au ion. Consequently, the proximity of the irreversibly adsorbed Au-adatoms on the already described Pt-nanostructured electrode. In acidic and alkaline solutions, the electrocatalytically activities toward methanol and glycerol oxidation were evaluated and is found to strongly on the surface of the gold-modified PtNPs. The PtNPs modified by Au electrode system used direct methanol fuel cell (DMFC) and direct glycerol fuel cell (DGFC). The DMFC and DGFC are much higher than in acid output in alkaline. Comparison of the i-E curves of nanostructure platinum electrode with that of a platinum nanostructure electrode modified by Au under similar conditions for the letter, the charge under the peak (i-E curve) in the oxidation region was higher. Furthermore, rough chronoamperometric measurements confirmed the results. The results of showed that the electrocatalytic properties of the nanostructured prepared surface were enhanced by the inclusion of gold adatoms with a variable extent of advancement. The current peak (Ip) and the current chronoamperometric (ICA) of glycerol oxidation on the PtNPs electrode modified by Au in acid media (130 mA/cm2, 47 µA/cm2) were higher than those of the bare PtNPs electrode and in alkaline media (171 mA/cm2, 66 µA/cm2). The stronger catalytic behavior in alkaline media of the Au-PtNP electrode indicates its promising use in alkaline direct alcohol cells.

Machine learning for detecting DNA attachment on SPR biosensor.

Optoelectric biosensors measure the conformational changes of biomolecules and their molecular interactions, allowing researchers to use them in different biomedical diagnostics and analysis activities. Among different biosensors, surface plasmon resonance (SPR)-based biosensors utilize label-free and gold-based plasmonic principles with high precision and accuracy, allowing these gold-based biosensors as one of the preferred methods. The dataset generated from these biosensors are being used in different machine learning (ML) models for disease diagnosis and prognosis, but there is a scarcity of models to develop or assess the accuracy of SPR-based biosensors and ensure a reliable dataset for downstream model development. Current study proposed innovative ML-based DNA detection and classification models from the reflective light angles on different gold surfaces of biosensors and associated properties. We have conducted several statistical analyses and different visualization techniques to evaluate the SPR-based dataset and applied t-SNE feature extraction and min-max normalization to differentiate classifiers of low-variances. We experimented with several ML classifiers, namely support vector machine (SVM), decision tree (DT), multi-layer perceptron (MLP), k-nearest neighbors (KNN), logistic regression (LR) and random forest (RF) and evaluated our findings in terms of different evaluation metrics. Our analysis showed the best accuracy of 0.94 by RF, DT and KNN for DNA classification and 0.96 by RF and KNN for DNA detection tasks. Considering area under the receiver operating characteristic curve (AUC) (0.97), precision (0.96) and F1-score (0.97), we found RF performed best for both tasks. Our research shows the potentiality of ML models in the field of biosensor development, which can be expanded to develop novel disease diagnosis and prognosis tools in the future.

Gold and silver as safe havens: A fractional integration and cointegration analysis.

This paper investigates whether gold and silver can be considered safe havens by examining their long-run linkages with 13 stock price indices. More specifically, the stochastic properties of the differential between gold/silver prices and 13 stock indices are analysed applying fractional integration/cointegration methods to daily data, first for a sample from January 2010 until December 2019, then for one from January 2020 until June 2022 which includes the Covid-19 pandemic. The results can be summarised as follows. In the case of the pre-Covid-19 sample ending in December 2019, mean reversion is found for the gold price differential only vis-à-vis a single stock index (SP500). whilst in seven other cases, although the estimated value of d is below 1, the value 1 is inside the confidence interval and thus the unit root null hypothesis cannot be rejected. In the remaining cases the estimated values of d are significantly higher than 1. As for the silver differential, the upper bound is 1 only in two cases, whilst in the others mean reversion does not occur. Thus, the evidence is mixed on whether these precious metals can be seen as safe havens, though it appears that this property characterises gold in a slightly higher number of cases. By contrast, when using the sample starting in January 2020, the evidence in favour of gold and silver as possible safe havens is pretty conclusive since mean reversion is only found in a single case, namely that of the gold differential vis-à-vis the New Zealand stock index.

A copper ion-mediated on-off-on gold nanocluster for pyrophosphate sensing and bioimaging in cells.

Herein, gold nanoclusters (AuNCs@EW@Lzm, AuEL) with the bright red fluorescence at 650 nm were prepared by egg white and lysozyme as double protein ligands, which exhibited good stability and high biocompatibility. The probe displayed highly selective detected pyrophosphate (PPi) based on Cu2+-mediated AuEL fluorescence quenching. Specifically, the fluorescence of AuEL was quenched once the Cu2+/Fe3+/Hg2+ is added to chelate with amino acids on the AuEL surface, respectively. Interestingly, the fluorescence of quenched AuEL-Cu2+ was significantly recovered by PPi, but not the other two. This phenomenon was attributed to the stronger bond between PPi and Cu2+ than that of Cu2+ with AuEL nanoclusters. The results demonstrated a good linear relationship between PPi concentration and the relative fluorescence intensity of AuEL-Cu2+ in the range of 131.00-685.40 µM with a detection limit of 2.56 µM. In addition, the quench AuEL-Cu2+ system can also be recovered in acidic environments (pH ≤ 5). And the as-synthesized AuEL showed excellent cell imaging and target the nucleus. Thus the fabrication of AuEL offers a facile strategy for efficient PPi assay and offers the potential for drug/gene delivery to the nucleus.

Cytotoxicity, uptake and accumulation of selenium nanoparticles and other selenium species in neuroblastoma cell lines related to Alzheimer's disease by using cytotoxicity assays, TEM and single cell-ICP-MS.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, representing 80% of the total dementia cases. The "amyloid cascade hypothesis" stablishes that the aggregation of the beta-amyloid protein (Aß42) is the first event that subsequently triggers AD development. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) have demonstrated excellent anti-amyloidogenic properties in previous works, leading to an improvement of AD aetiology. Here, the in vitro effect of selenium species in AD model cell line has been study to obtain a better assessment of their effects in AD treatment. For this purpose, mouse neuroblastoma (Neuro-2a) and human neuroblastoma (SH-SY5Y) cell lines were used. Cytotoxicity of selenium species, such as selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys) and Ch-SeNPs, has been determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry methods. Intracellular localisation of Ch-SeNPs, and their pathway through SH-SY5Y cell line, have been evaluated by transmission electron microscopy (TEM). The uptake and accumulation of selenium species by both neuroblastoma cell lines have been quantified at single cell level by single cell- Inductively Coupled Plasma with Mass Spectrometry detection (SC-ICP-MS), with a previous optimisation of transport efficiency using gold nanoparticles (AuNPs) ((69 ± 3) %) and 2.5 mm calibration beads ((92 ± 8) %). Results showed that Ch-SeNPs would be more readily accumulated by both cell lines than organic species being accumulation ranges between 1.2 and 89.5 fg Se cell-1 for Neuro-2a and 3.1-129.8 fg Se cell-1 for SH-SY5Y exposed to 250 µM Ch-SeNPs. Data obtained were statistically treated using chemometric tools. These results provide an important insight into the interaction of Ch-SeNPs with neuronal cells, which could support their potential use in AD treatment.

Golden Chanterelle or a Gold Mine? Metabolites from Aqueous Extracts of Golden Chanterelle (Cantharellus cibarius) and Their Antioxidant and Cytotoxic Activities.

Cantharellus cibarius, the golden chanterelle, is the second most-collected wild edible mushroom in Europe and very frequently harvested in Croatia. Wild mushrooms have been considered a healthy food since ancient times and are today highly valued for their beneficial nutritional as well as medicinal properties. Since golden chanterelle is added to different food products to improve their nutritive value, we studied the chemical profile of aqueous extracts of golden chanterelle (at 25 °C and 70 °C) and their antioxidant and cytotoxic activities. Malic acid, pyrogallol and oleic acid were some of the main compounds identified by GC-MS from derivatized extract. p-Hydroxybenzoic acid, protocatechuic acid and gallic acid were the most abundant phenolics quantitatively determined by HPLC, with somewhat higher amounts for samples extracted at 70 °C. Antioxidant activity was determined by ferric reducing antioxidant power assay and oxygen radical absorption method, and the highest results were recorded for golden chanterelle extracted at 70 °C, being 41.54 ± 1.54 and 38.72 ± 2.47 µM TE/L, respectively. Aqueous extract at 25 °C showed the better response against human breast adenocarcinoma MDA-MB-231 (IC50 = 375µg/mL). Our results confirm the beneficial effect of golden chanterelle even under aqueous extraction conditions and highlight its significance as a dietary supplement and in the development of new beverage products.

Design of Novel Phosphatidylinositol 3-Kinase Inhibitors for Non-Hodgkin's Lymphoma: Molecular Docking, Molecular Dynamics, and Density Functional Theory Studies on Gold Nanoparticles.

Non-Hodgkin's lymphomas are a diverse collection of lymphoproliferative cancers that are much less predictable than Hodgkin's lymphomas with a far greater tendency to metastasize to extranodal sites. A quarter of non-Hodgkin's lymphoma cases develop at extranodal sites and the majority of them involve nodal and extranodal sites. The most common subtypes include follicular lymphoma, chronic/small lymphocytic leukaemia, mantel cell lymphoma, and marginal zone lymphoma. Umbralisib is one of the latest PI3Kδ inhibitors in clinical trials for several hematologic cancer indications. In this study, new umbralisib analogues were designed and docked to the active site of PI3Kδ, the main target of the phosphoinositol-3-kinase/Akt/mammalian target of the rapamycin pathway (PI3K/AKT/mTOR). This study resulted in eleven candidates, with strong binding to PI3Kδ with a docking score between -7.66 and -8.42 Kcal/mol. The docking analysis of ligand-receptor interactions between umbralisib analogues bound to PI3K showed that their interactions were mainly controlled by hydrophobic interactions and, to a lesser extent, by hydrogen bonding. In addition, the MM-GBSA binding free energy was calculated. Analogue 306 showed the highest free energy of binding with -52.22 Kcal/mol. To identify the structural changes and the complexes' stability of proposed ligands, molecular dynamic simulation was used. Based on this research finding, the best-designed analogue, analogue 306, formed a stable ligand-protein complex. In addition, pharmacokinetics and toxicity analysis using the QikProp tool demonstrated that analogue 306 had good absorption, distribution, metabolism, and excretion properties. Additionally, it has a promising predicted profile in immune toxicity, carcinogenicity, and cytotoxicity. In addition, analogue 306 had stable interactions with gold nanoparticles that have been studied using density functional theory calculations. The best interaction with gold was observed at the oxygen atom number 5 with -29.42 Kcal/mol. Further in vitro and in vivo investigations are recommended to be carried out to verify the anticancer activity of this analogue.

Tectomer-Mediated Optical Nanosensors for Tyramine Determination.

The development of optical sensors for in situ testing has become of great interest in the rapid diagnostics industry. We report here the development of simple, low-cost optical nanosensors for the semi-quantitative detection or naked-eye detection of tyramine (a biogenic amine whose production is commonly associated with food spoilage) when coupled to Au(III)/tectomer films deposited on polylactic acid (PLA) supports. Tectomers are two-dimensional oligoglycine self-assemblies, whose terminal amino groups enable both the immobilization of Au(III) and its adhesion to PLA. Upon exposure to tyramine, a non-enzymatic redox reaction takes place in which Au(III) in the tectomer matrix is reduced by tyramine to gold nanoparticles, whose reddish-purple color depends on the tyramine concentration and can be identified by measuring the RGB coordinates (Red-Green-Blue coordinates) using a smartphone color recognition app. Moreover, a more accurate quantification of tyramine in the range from 0.048 to 10 µM could be performed by measuring the reflectance of the sensing layers and the absorbance of the characteristic 550 nm plasmon band of the gold nanoparticles. The relative standard deviation (RSD) of the method was 4.2% (n = 5) with a limit of detection (LOD) of 0.014 µM. A remarkable selectivity was achieved for tyramine detection in the presence of other biogenic amines, especially histamine. This methodology, based on the optical properties of Au(III)/tectomer hybrid coatings, is promising for its application in food quality control and smart food packaging.