Pattern recognition of multiple metal ions using fluorescent Perylenyl nanoaggregates and application in food traceability.

Metal ions (MIs) identification is essential for the safety assessment, traceability and authentication of food. Most current approaches for detecting MIs are difficult to reconcile the simplicity, sensitivity and stability simultaneously. In this work, we proposed a novel strategy for discriminating MIs based on fluorescent supramolecular nanoaggregates (SNAs). In the presence of MI, perylene diimide derivatives (PDI)-based SNAs could be formed through the multiple non-covalent interactions between them including electrostatic, coordination and π-π interactions. With the assistance of discriminant analysis (LDA), different MIs (Hg2+, Ag+, Cd2+, Fe3+, Cr3+, Fe2+, Zn2+, Cu2+ and Pb2+) were successfully identified at three different concentration levels. It featured good quantitative sensing abilities in buffer solutions and practical samples. Furthermore, a water-quality evaluation model was successfully constructed for the distinction of different sources of drinking water, and the fluorescence array sensor technology was applied for the first time to the geographical traceability of apples.

Round robin experiment to detect, size, and characterize flaws in the welds of existing hydraulic steel structures using phased array ultrasonic testing.

Limited information exists on the ability of nondestructive testing techniques to detect, size, and characterize flaws in existing hydraulic steel structures (HSS). Round robin experiments were conducted using phased array ultrasonics to inspect welded steel specimens representing joints in existing HSS. Technicians detected 83% of the flaws scanned, but detection rates varied widely by flaw and technician. Uncertainty in flaw size estimates, represented by 90% confidence bounds on the ratio of estimated to actual length or height, ranged from 0.52 to 2.10 for length and 0.32 to 3.59 for height. Planar, volumetric and laminar flaws were accurately characterized 80% of the time.

2q31 microdeletion syndrome with the velocardiofacial phenotype and review of the literature: a case report.

BACKGROUND: The 2q31 deletion results in a distinct phenotype characterized by varying degrees of developmental delay, short stature, facial dysmorphism, and variable limb defects. Dysmorphic features include microcephaly, downslanting palpebral fissures, a long and flat philtrum, micrognathia, and dysplastic, low-set ears. To date, comparative genomic hybridization has identified this deletion in 38 patients. Consequently, additional patients with comprehensive clinical data are required to fully understand the spectrum of clinical manifestation associated with a deletion in the 2q31 cytoband. CASE PRESENTATION: We present the case of an 8-year-old female patient with clinical features of velocardiofacial syndrome, which include facial dysmorphism, congenital heart disease (persistent truncus arteriosus and ostium secundum-type atrial septal defect), and a seizure syndrome. Array comparative genomic hybridization revealed a non-continous deletion spanning cytobands 2q31.1-to 2q31.3, confirming a diagnosis of 2q31 microdeletion syndrome. The patient has undergone supportive therapies for swallowing and speech. Additionally, we provide a review of the literature on previous cases to give context. CONCLUSION: In this report, we present the first documented case of a complex, discontinuous deletion spanning in the 2q31-2q32 regions. This case contributes to our understanding of the phenotypic and mutational spectrum observed in individuals with deletions in these cytobands. It underscores the significance of employing high-resolution techniques and comprenhensive analysis in diagnosing patients with complex phenotypes. Such approaches are crucial for differentiating this condition from more common microdeletion syndromes, such as the 22q11 deletion syndrome.

A 1024-Channel 268 nW/pixel 36×36 µm2/channel Data-Compressive Neural Recording IC for High-Bandwidth Brain-Computer Interfaces.

This paper presents a data-compressive neural recording IC for single-cell resolution high-bandwidth brain-computer interfaces. The IC features wired-OR lossy compression during digitization, thus preventing data deluge and massive data movement. By discarding unwanted baseline samples of the neural signals, the output data rate is reduced by 146× on average while allowing the reconstruction of spike samples. The recording array consists of pulse position modulation-based active digital pixels with a global single-slope analog-to-digital conversion scheme, which enables a low-power and compact pixel design with significantly simple routing and low array readout energy. Fabricated in a 28-nm CMOS process, the neural recording IC features 1024 channels (i.e., 32 × 32 array) with a pixel pitch of 36 µm that can be directly matched to a high-density microelectrode array. The pixel achieves 7.4 µVrms input-referred noise with a -3 dB bandwidth of 300-Hz to 5-kHz while consuming only 268 nW from a single 1-V supply. The IC achieves the smallest area per channel (36 × 36 µm2) and the highest energy efficiency among the state-of-the-art neural recording ICs published to date.

Molecular genetic characterization of myeloid neoplasms with idic(X)(q13) and i(X)(q10).

Background/Aim: Isodicentric [idic(X)(q13)] and isochromosome [i(X)(q10)] are infrequent aberrations in neoplastic diseases. The former is mainly reported in elderly women with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), whereas the latter is mostly found as a secondary aberration or part of complex karyotypes in various types of neoplasms, including MDS and AML. Here, we present the molecular genetics and clinical features of six patients with myeloid neoplasia and the above-mentioned aberrations. Patients and Methods: Array comparative genome hybridization (aCGH) and next-generation sequencing (NGS) myeloid panel were used to examine genetic alterations in five bone marrow samples containing neoplastic cells carrying idic(X)(q13) and one sample with i(X)(q10). Results: The breakpoints of idic(X)(q13) were clustered within a 200 kbp region encompassing FAM236B, DMRTC1B, and DMRTC1. The breakpoint of i(X)(q10) was identified within a 112 kbp region on sub-band p11.22 containing SSX2, SSX2B, and SPANXN5. Pathogenic variants of TET2 were identified in four cases, SF3B1 in three cases, ASXL1 and SRSF2 in two cases each, whereas STAG2, RUNX1, U2AF1, and TP53 pathogenic variants were detected in only single cases. Conclusions: The breakpoints of idic(X)(q13) are within a 200kbp. i(X)(q10) in our study turned out to be a cryptic idic(X)(p11) aberration, reported for the first time here. TET2, SF3B1, ASXL1, or SRSF2 were highly prevalent in patients with idic(X)(q13)/i(X)(q10) abnormalities and were often associated with a worse prognosis.

Diagnostic and prognostic role of soft ultrasound markers in prenatal detection and assessment of foetal abnormalities.

Various soft markers can be detected in the ultrasonography of foetuses, which can be related to chromosomal abnormalities and increases the risk of abnormalities, or they can be considered as normal variations that can disappear due to the pregnancy progress. There are different tools to detect chromosomal abnormalities like conventional karyotyping, chromosomal microarray analysis (CMA), single nucleotide polymorphism (SNP) array, non-invasive prenatal test (NIPT), and non-invasive prenatal screening (NIPS). Therefore, in the present study, we aim to assess the accuracy of ultrasonic soft markers in the diagnosis of chromosomal abnormalities such as chromosomal structural abnormalities, aneuploidy, and triploidy, especially Trisomy 21 and Trisomy 18. A systemic literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science. We gathered all articles published before August 2023. We selected English studies such as retrospective and cross-sectional ones that assessed the relationship between ultrasonic soft markers and foetal chromosomal abnormalities. A total of 10 articles with 18,580 cases were included in our systematic review article that assessed the foetal abnormalities and aneuploidies by using conventional karyotyping, SNP array, CMA, and NIPT (or NIPS). Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common abnormalities related to ultrasonic soft markers by karyotyping; however, Trisomy 13, 47, XXY, 45, X, and mosaic chromosomal abnormalities were other abnormalities detected. Results by CMA showed Trisomy 21 and Trisomy 18 as the most common abnormalities in the foetuses also with ultrasonic soft markers, and other abnormalities were pathogenic copy-number variations, Turner (XO), polyploidy, 22q11.2deletion, and Trisomy13, respectively. It was discovered that there is a greater possibility of having pathogenic copy number variations (CNVs) in the groups with multiple ultrasonic soft markers, while foetuses with ultrasonic soft markers have a decreased prevalence of CMA abnormality compared to those who had significant abnormalities or abnormal nuchal translucency. Trisomy 21 was the only abnormality found by NIPT in the groups with 1 and 2 soft markers, while groups with multiple soft markers were all normal. By using SNP array, it was identified that the rate of chromosomal abnormalities such as aneuploidy and triploidy, LOH, and CNVs was lower in the group with a single ultrasonic soft marker compared to the group with structural abnormalities in multiple systems. Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common chromosomal abnormalities that ultrasound soft markers could diagnose. Therefore, it is recommended to employ soft markers besides CMA, SNP array, and NIPS (or NIPT) for greater accuracy in detecting foetus abnormalities.

A non-classical synthetic strategy for organic mesocrystals.

Mesocrystals are ordered nanoparticle superstructures, often with internal porosity, which receive much recent research interest in catalysis, energy storage, sensors, and biomedicine area. Understanding the mechanism of synthetic routes is essential for precise control of size and structure that affect the function of mesocrystals. The classical synthetic strategy of mesocrystal was formed via self-assembly of nanoparticles with a faceted inorganic core but a denser (or thicker) shell of organic molecules. However, the potential materials and synthetic handles still need to be explored to meet new applications. In this work, we develop a non-classical synthetic strategy for organic molecules, such as tetrakis (4-hydroxyphenyl) ethylene (TPE-4OH), tetrakis (4-bromophenyl) ethylene (TPE-4Br), and benzopinacole, to produce mesocrystals with composed of microrod arrays via co-solvent-induced crystal transformation. The aligned nanorods are grown epitaxially onto organic microplates, directed by small lattice mismatch between plates and rods. Thus, the present work offers general synthetic handle for establishing well-organized organic mesocrystals.

Development of an evaluation method for addictive compounds based on electrical activity of human iPS cell-derived dopaminergic neurons using microelectrode array.

Addiction is known to occur through the consumption of substances such as pharmaceuticals, illicit drugs, food, alcohol and tobacco. These addictions can be viewed as drug addiction, resulting from the ingestion of chemical substances contained in them. Multiple neural networks, including the reward system, anti-reward/stress system and central immune system in the brain, are believed to be involved in the onset of drug addiction. Although various compound evaluations using microelectrode array (MEA) as an in vitro testing methods to evaluate neural activities have been conducted, methods for assessing addiction have not been established. In this study, we aimed to develop an in vitro method for assessing the addiction of compounds, as an alternative to animal experiments, using human iPS cell-derived dopaminergic neurons with MEA measurements. MEA data before and after chronic exposure revealed specific changes in addictive compounds compared to non-addictive compounds, demonstrating the ability to estimate addiction of compound. Additionally, conducting gene expression analysis on cultured samples after the tests revealed changes in the expression levels of various receptors (nicotine, dopamine and GABA) due to chronic administration of addictive compounds, suggesting the potential interpretation of these expression changes as addiction-like responses in MEA measurements. The addiction assessment method using MEA measurements in human iPS cell-derived dopaminergic neurons conducted in this study proves effective in evaluating addiction of compounds on human neural networks.

Distinct copy number signatures between residual benign and transformed areas of carcinoma ex pleomorphic adenoma.

The mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses (p = 0.187) and amplifications (p = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas (p = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7, ERBB2, HMGA2, and RPSAP52.

Development and validation of a multi-marker liquid bead array assay for the simultaneous detection of PIK3CA and ESR1 hotspot mutations in single circulating tumor cells (CTCs).

Background: PIK3CA and ESR1 mutations are associated with progression and therapy resistance in metastatic breast cancer (MBC). CTCs are highly heterogeneous and their analysis at single cell level can provide unique information for mutational profiling and the existence of different sub-clones related to tumor progression. We have developed a novel multi-marker liquid bead array assay based on combination of an enzymatic mutation enrichment method, multiplex PCR-based assay, and liquid bead array technology for the simultaneous detection of PIK3CA and ESR1 hotspot mutations in liquid biopsy samples. We focus on single CTCs, however the assay can be used for bulk CTC and ctDNA analysis. Materials and methods: Single CTCs were isolated from an ER+/HER2+ MBC patient from CellSearch® cartridges using the VyCAP Puncher System and subjected to whole genome amplification followed by nuclease-assisted minor-allele enrichment with probe-overlap (NaME-PrO) enrichment. The assay was validated for analytical sensitivity and specificity for the simultaneous detection of PIK3CA (E545K, E542K, H1047R, H1047L) and ESR1 (Y537S, Y537C, Y537N, D538G, L536H) mutations in single CTCs, while its clinical performance was evaluated on 22 single CTCs and three single white blood cells (WBCs). Results: The developed multi-marker liquid bead array assay is novel, highly specific and sensitive for both mutation panels. The assay can reliably detect mutation-allelic-frequencies (MAFs) as low as 0.1 %. The presence of PIK3CA and ESR1 mutations was detected in 13.6 % and 72.7 % of single CTCs, respectively. The developed assay is sample-saving since it requires only 2 µL of amplified DNA to check for nine hotspot PIK3CA and ESR1 mutations in a single cell. The developed liquid bead array assay (Luminex, US), based on a 96 microwell plate format, enables the simultaneous analysis of 96 single cells. Conclusions: The developed novel multi-marker liquid bead array assay for the simultaneous detection of PIK3CA and ESR1 hotspot mutations in single CTCs is highly specific, highly sensitive, high-throughput, and sample-, cost-, and time-saving. This multi-marker liquid bead array assay can be extended to detect up to 100 mutations in many genes at once and can be applied for bulk CTC and ctDNA analysis.

A human lectin array for characterizing host-pathogen interactions.

A human lectin array has been developed to probe the interactions of innate immune receptors with pathogenic and commensal micro-organisms. Following the successful introduction of a lectin array containing all of the cow C-type carbohydrate-recognition domains (CRDs), a human array described here contains the C-type CRDs as well as CRDs from other classes of sugar-binding receptors, including galectins, siglecs, R-type CRDs, ficolins, intelectins and chitinase-like lectins. The array is constructed with CRDs modified with single-site biotin tags, ensuring that the sugar-binding sites in CRDs are displayed on a streptavidin-coated surface in a defined orientation and are accessible to the surfaces of microbes. A common approach used for expression and display of CRDs from all of the different structural categories of glycan-binding receptors allows comparisons across lectin families. In addition to previously documented protocols for binding of fluorescently-labeled bacteria, methods have been developed for detecting unlabeled bacteria bound to the array by counter-staining with DNA-binding dye. Screening has also been undertaken with viral glycoproteins and bacterial and fungal polysaccharides. The array provides an unbiased screen for sugar ligands that interact with receptors and many show binding not anticipated from earlier studies. For example, some of the galectins bind with high affinity to bacterial glycans that lack lactose or N-acetyllactosamine. The results demonstrate the utility of the human lectin array for providing a unique overview of the interactions of multiple classes of glycan-binding proteins in the innate immune system with different types of micro-organisms.

Comprehensive molecular and clinical findings in 29 patients with multi-locus imprinting disturbance.

BACKGROUND: Multi-locus imprinting disturbance (MLID) with methylation defects in various differentially methylated regions (DMRs) has recently been identified in approximately 150 cases with imprinting disorders (IDs), and deleterious variants have been found in genes related to methylation maintenance of DMRs, such as those encoding proteins constructing the subcortical maternal complex (SCMC), in a small fraction of patients and/or their mothers. However, integrated methylation analysis for DMRs and sequence analysis for MLID-causative genes in MLID cases and their mothers have been performed only in a single study focusing on Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) phenotypes. RESULTS: Of 783 patients with various IDs we have identified to date, we examined a total of 386 patients with confirmed epimutation and 71 patients with epimutation or uniparental disomy. Consequently, we identified MLID in 29 patients with epimutation confirmed by methylation analysis for multiple ID-associated DMRs using pyrosequencing and/or methylation-specific multiple ligation-dependent probe amplification. MLID was detected in approximately 12% of patients with BWS phenotype and approximately 5% of patients with SRS phenotype, but not in patients with Kagami-Ogata syndrome, Prader-Willi syndrome, or Angelman syndrome phenotypes. We next conducted array-based methylation analysis for 78 DMRs and whole-exome sequencing in the 29 patients, revealing hypomethylation-dominant aberrant methylation patterns in various DMRs of all the patients, eight probably deleterious variants in genes for SCMC in the mothers of patients, and one homozygous deleterious variant in ZNF445 in one patient. These variants did not show gene-specific methylation disturbance patterns. Clinically, neurodevelopmental delay and/or intellectual developmental disorder (ND/IDD) was observed in about half of the MLID patients, with no association with the identified methylation disturbance patterns and genetic variants. Notably, seven patients with BWS phenotype were conceived by assisted reproductive technology (ART). CONCLUSIONS: The frequency of MLID was 7.5% (29/386) in IDs caused by confirmed epimutation. Furthermore, we revealed diverse patterns of hypomethylation-dominant methylation defects, nine deleterious variants, ND/IDD complications in about half of the MLID patients, and a high frequency of MLID in ART-conceived patients.

Defining Cardiomyocyte Repolarization Response to Pharmacotherapy in Long-QT Syndrome Type 3.

BACKGROUND: Long-QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient-specific, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes model of long-QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge. METHODS AND RESULTS: HiPSCs were generated from a patient with LQT3 harboring an SCN5A pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same SCN5A pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9 gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient-derived LQT3 (SCN5A+/-) and genetically engineered LQT3 (SCN5A+/-) hiPSC-derived cardiomyocytes showed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage-gated sodium channel (NaV1.5) blocker, shortened repolarization in both patient-derived LQT3 and genetically engineered LQT3 hiPSC-derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose-dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect in vitro, but the LQT3 clones were not more disproportionately affected compared with the control. CONCLUSIONS: We demonstrated that patient-derived and genetically engineered LQT3 hiPSC-derived cardiomyocytes faithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an in vitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient-specific approach in high-risk patients with LQT3.

Picosecond Alexandrite Laser With Diffractive Lens Array Combined With Long-Pulse Alexandrite Laser for the Treatment of Facial Photoaging in Chinese Women: A Retrospective Study.

BACKGROUND AND OBJECTIVES: Facial photoaging is a type of facial skin aging induced mainly by exogenous factors (ultraviolet radiation) and often manifests itself in the form of hyperpigmentation, telangiectasia, roughness, increase in fine lines/wrinkles, and enlarged pores. Recently, picosecond lasers have become an emerging option for the treatment of facial photoaging, and long-pulse alexandrite lasers (LPAL) have demonstrated promising potential in the treatment of photoaging-related symptoms. This study aimed to evaluate the efficacy and safety of picosecond alexandrite laser (PSAL) with diffractive lens array (DLA) combined with LPAL for facial photoaging. METHODS: This is a retrospective study of 20 Chinese female patients with facial photoaging who received PSAL with DLA combined with LPAL during a 1-year period. All patients were treated every 4 weeks for a total of three treatments. Objective indicators of facial photoaging and patient satisfaction were evaluated before each treatment, and pain scores and adverse effects were recorded after each treatment. RESULTS: Compared with baseline, patients showed significant differences in all facial photoaging indices (p < 0.01). After receiving three treatments, there was a 20.1% decrease in the pigmentation index, a 23.9% decrease in the erythema index, a 34.5% decrease in the texture index, a 28.4% decrease in the fine lines index, a 56% decrease in the pore index, a 9.3% elevation and a 17.1% decrease in elasticity R2 and F4, respectively, and a 55% decrease in sebum content. The mean satisfaction score for the three treatments was 4.67 (3.33, 5.00), and the mean visual analogue scale (VAS) pain score was 7.00. No serious adverse effects such as post-inflammatory hyperpigmentation (PIH), hypopigmentation, or blistering were observed at the treatment site during the treatment period. CONCLUSION: PSAL with DLA combined with LPAL for the treatment of facial photoaging with significant efficacy, high patient satisfaction, and minimal adverse effects.

Gold Nanorod-Embedded PDMS Micro-Pillar Array for Localized Photothermal Stimulation.

Gold nanorods (GNRs) are one of the most promising biomaterial choices for the photothermal activation of neurons due to their relative biocompatibility, unique photothermal properties, and broad optical tunability through their synthetic shape control. While photothermal stimulation using randomly accumulated GNRs successfully demonstrates the potential treatment of functional neural disorders by modulating the neuronal activities using localized heating, there are limited demonstrations to translate this new concept into large-arrayed neural stimulations. In this paper, we report an arrayed PDMS micropillar platform in which GNRs are embedded as pixel-like, arrayed photothermal stimulators at the tips of the pillars. The proposed platform will be able to localize GNRs at predetermined pillar positions and create thermal stimulations using near-infrared (NIR) light. This will address the limitations of randomly distributed GNR-based approaches. Furthermore, a flexible PDMS pillar structure will create intimate interfaces on target cells. By characterizing the spatiotemporal temperature change in the platform with rhodamine B dye, we have shown that the localized temperature can be optically modulated within 4°C, which is in the range of temperature variation required for neuromodulation using NIR light. We envision that our proposed platform has the potential to be applied as a photothermal, neuronal stimulation interface with high spatiotemporal resolution.

Energy stress induced cardiac autophagy detection via a chronic and dynamic cardiomyocytes-based biosensing platform.

Hypoglycemia is a common complication which occurs during the treatment of diabetes, closely associated with cardiovascular events. A sudden decrease in blood glucose increases the risk of arrhythmia, which can lead to sudden cardiac death. This event is usually accompanied by abnormal electrophysiological activities in cardiomyocytes. However, traditional models do not efficiently reflect real-time cardiomyocyte electrophysiological changes under various glucose deprivation conditions in a large-scale and high-throughput manner. Therefore, we need to develop a new biosensing platform to aid in related scientific research. In this study, a cardiomyocyte-based biosensor was developed for real-time, noninvasive monitoring of the electrophysiological responses of cardiomyocytes under different glucose concentrations. The findings show that low-glucose conditions result in abnormal electrophysiology in cardiomyocytes, but autophagy enables cells to survive this adversity. Inhibition of autophagy exacerbates electrophysiological abnormalities, and long-term glucose starvation causes irreversible damage to cardiomyocytes. The proposed chronic and dynamic cardiomyocyte-based biosensing platform provides a new tool for understanding the effects of hypoglycemia on the in vitro cardiomyocyte-based heart model, revealing that autophagy has the potential to be an alternative treatment for diabetes and hypoglycemia.

ß-amyloid's neurotoxic mechanisms as defined by in vitro microelectrode arrays: a review.

Alzheimer's disease is characterised by the aggregation of ß-amyloid, a pathological feature believed to drive the neuronal loss and cognitive decline commonly seen in the disease. Given the growing prevalence of this progressive neurodegenerative disease, understanding the exact mechanisms underlying this process has become a top priority. Microelectrode arrays are commonly used for chronic, non-invasive recording of both spontaneous and evoked neuronal activity from diverse in vitro disease models and to evaluate therapeutic or toxic compounds. To date, microelectrode arrays have been used to investigate ß-amyloids' toxic effects, ß-amyloids role in specific pathological features and to assess pharmacological approaches to treat Alzheimer's disease. The versatility of microelectrode arrays means these studies use a variety of methods and investigate different disease models and brain regions. This review provides an overview of these studies, highlighting their disparities and presenting the status of the current literature. Despite methodological differences, the current literature indicates that ß-amyloid has an inhibitory effect on synaptic plasticity and induces network connectivity disruptions. ß-amyloid's effect on spontaneous neuronal activity appears more complex. Overall, the literature corroborates the theory that ß-amyloid induces neurotoxicity, having a progressive deleterious effect on neuronal signalling and plasticity. These studies also confirm that microelectrode arrays are valuable tools for investigating ß-amyloid pathology from a functional perspective, helping to bridge the gap between cellular and network pathology and disease symptoms. The use of microelectrode arrays provides a functional insight into Alzheimer's disease pathology which will aid in the development of novel therapeutic interventions.

Self-Standing Mo/MoO2 Porous Flake Arrays for Efficient Hydrogen Evolution Reaction in High-pH Media.

The alkaline hydrogen evolution reaction (HER) is limited by scarce proton availability, resulting in slower reaction kinetics compared to those under acidic conditions. Enhancing the local chemical environment of protons on the catalyst surface can improve the intrinsic reaction kinetics. Here, we design a Mo/MoO2 metallic heterojunction that creates an acidic-like environment with a proton-rich surface, significantly enhancing HER performance in alkaline electrolytes, as confirmed by in situ spectroscopy and electrochemical analysis. A self-standing Mo/MoO2 catalytic electrode is fabricated via a controlled pyrolysis-reduction strategy. This electrode exhibits exceptional HER activity, with low overpotentials of 65 mV at 10 mA cm-2 and 315 mV at 500 mA cm-2, a Tafel slope of 38.2 mV dec-1, and stability exceeding 60 h at -300 mA cm-2 in alkaline solution. The porous flake array structure of the Mo/MoO2 heterojunctions enhances the adjacent hydronium (H3O+) concentration, resulting in a ΔGH* value of 0.15 eV and a water dissociation energy barrier of 0.37 eV in an alkaline medium. The successful preparation of a large-area electrode (2 cm × 2 cm) demonstrates the scalability of this approach for fabricating molybdenum-based catalytic electrodes with enhanced HER activity in alkaline environments.

Graph neural networks in multi-stained pathological imaging: extended comparative analysis of Radiomic features.

PURPOSE: This study investigates the application of Radiomic features within graph neural networks (GNNs) for the classification of multiple-epitope-ligand cartography (MELC) pathology samples. It aims to enhance the diagnosis of often misdiagnosed skin diseases such as eczema, lymphoma, and melanoma. The novel contribution lies in integrating Radiomic features with GNNs and comparing their efficacy against traditional multi-stain profiles. METHODS: We utilized GNNs to process multiple pathological slides as cell-level graphs, comparing their performance with XGBoost and Random Forest classifiers. The analysis included two feature types: multi-stain profiles and Radiomic features. Dimensionality reduction techniques such as UMAP and t-SNE were applied to optimize the feature space, and graph connectivity was based on spatial and feature closeness. RESULTS: Integrating Radiomic features into spatially connected graphs significantly improved classification accuracy over traditional models. The application of UMAP further enhanced the performance of GNNs, particularly in classifying diseases with similar pathological features. The GNN model outperformed baseline methods, demonstrating its robustness in handling complex histopathological data. CONCLUSION: Radiomic features processed through GNNs show significant promise for multi-disease classification, improving diagnostic accuracy. This study's findings suggest that integrating advanced imaging analysis with graph-based modeling can lead to better diagnostic tools. Future research should expand these methods to a wider range of diseases to validate their generalizability and effectiveness.