Thermal conductance calculations of silicon nanowires: comparison with diamond nanowires

We present phonon thermal conductance calculations for silicon nanowires (SiNWs) with diameters ranging from 1 to 5 nm with and without vacancy defects by the non-equilibrium Green’s function technique using the interatomic Tersoff-Brenner potentials. For the comparison, we also present phonon thermal conductance calculations for diamond nanowires. For two types of vacancy defects in the SiNW, a ‘center defect’ and a ‘surface defect’, we found that a center-defect reduces thermal conductance much more than a surface defect. We also found that the thermal conductance changes its character from the usual behavior, in proportion to the square of diameter (the cross-sectional area) for over 100 and 300 K, to the unusual one, not dependent on its diameter at all at low temperature. The crossover is attributed to the quantization of thermal conductance.     

The Study of Quantum Interference in Metallic Photonic Crystals Doped with Four-Level Quantum Dots

In this work, the absorption coefficient of a metallic photonic crystal doped with nanoparticles has been obtained using numerical simulation techniques. The effects of quantum interference and the concentration of doped particles on the absorption coefficient of the system have been investigated. The nanoparticles have been considered as semiconductor quantum dots which behave as a four-level quantum system and are driven by a single coherent laser field. The results show that changing the position of the photonic band gap about the resonant energy of the two lower levels directly affects the decay rate, and the system can be switched between transparent and opaque states if the probe laser field is tuned to the resonance frequency. These results provide an application for metallic nanostructures in the fabrication of new optical switches and photonic devices.     

Fabrication of porous silicon nanowires by MACE method in HF/H2O2/AgNO3 system at room temperature

In this paper, the moderately and lightly doped porous silicon nanowires (PSiNWs) were fabricated by the ‘one-pot procedure’ metal-assisted chemical etching (MACE) method in the HF/H₂O₂/AgNO₃ system at room temperature. The effects of H₂O₂ concentration on the nanostructure of silicon nanowires (SiNWs) were investigated. The experimental results indicate that porous structure can be introduced by the addition of H₂O₂ and the pore structure could be controlled by adjusting the concentration of H₂O₂. The H₂O₂ species replaces Ag⁺ as the oxidant and the Ag nanoparticles work as catalyst during the etching. And the concentration of H₂O₂ influences the nucleation and motility of Ag particles, which leads to formation of different porous structure within the nanowires. A mechanism based on the lateral etching which is catalyzed by Ag particles under the motivation by H₂O₂ reduction is proposed to explain the PSiNWs formation.     

Genes Implicated in Familial Parkinson’s Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage

The mechanism of nigral dopaminergic neuronal degeneration in Parkinson’s disease (PD) is unknown. One of the pathological characteristics of the disease is the deposition of α-synuclein (α-syn) that occurs in the brain from both familial and sporadic PD patients. This paper constitutes a narrative review that takes advantage of information related to genes (SNCA, LRRK2, GBA, UCHL1, VPS35, PRKN, PINK1, ATP13A2, PLA2G6, DNAJC6, SYNJ1, DJ-1/PARK7 and FBXO7) involved in familial cases of Parkinson’s disease (PD) to explore their usefulness in deciphering the origin of dopaminergic denervation in many types of PD. Direct or functional interactions between genes or gene products are evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The rationale is to propose a map of the interactions between SNCA, the gene encoding for α-syn that aggregates in PD, and other genes, the mutations of which lead to early-onset PD. The map contrasts with the findings obtained using animal models that are the knockout of one of those genes or that express the mutated human gene. From combining in silico data from STRING-based assays with in vitro and in vivo data in transgenic animals, two likely mechanisms appeared: (i) the processing of native α-syn is altered due to the mutation of genes involved in vesicular trafficking and protein processing, or (ii) α-syn mutants alter the mechanisms necessary for the correct vesicular trafficking and protein processing. Mitochondria are a common denominator since both mechanisms require extra energy production, and the energy for the survival of neurons is obtained mainly from the complete oxidation of glucose. Dopamine itself can result in an additional burden to the mitochondria of dopaminergic neurons because its handling produces free radicals. Drugs acting on G protein-coupled receptors (GPCRs) in the mitochondria of neurons may hopefully end up targeting those receptors to reduce oxidative burden and increase mitochondrial performance. In summary, the analysis of the data of genes related to familial PD provides relevant information on the etiology of sporadic cases and might suggest new therapeutic approaches.     

Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.     

Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage

Transgenic modification of the two most common genes (APPsw, PS1ΔE9) related to familial Alzheimer’s disease (AD) in rats has produced a rodent model that develops pathognomonic signs of AD without genetic tau-protein modification. We used 17-month-old AD rats (n = 8) and age-matched controls (AC, n = 7) to evaluate differences in sleep behavior and EEG features during wakefulness (WAKE), non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) over 24-h EEG recording (12:12h dark–light cycle). We discovered that AD rats had more sleep–wake transitions and an increased probability of shorter REM and NREM bouts. AD rats also expressed a more uniform distribution of the relative spectral power. Through analysis of information content in the EEG using entropy of difference, AD animals demonstrated less EEG information during WAKE, but more information during NREM. This seems to indicate a limited range of changes in EEG activity that could be caused by an AD-induced change in inhibitory network function as reflected by increased GABAAR-β2 expression but no increase in GAD-67 in AD animals. In conclusion, this transgenic rat model of Alzheimer’s disease demonstrates less obvious EEG features of WAKE during wakefulness and less canonical features of sleep during sleep.     

Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.     

Histone Methylation Regulation in Neurodegenerative Disorders

Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation and histone posttranslational modifications, which are critical for gene expression in almost all tissues and in brain health and disease. These advances have influenced much interest in understanding the dysregulation of epigenetic mechanisms in neurodegenerative disorders. Although these disorders diverge in their fundamental causes and pathophysiology, several involve the dysregulation of histone methylation-mediated gene expression. Interestingly, epigenetic remodeling via histone methylation in specific brain regions has been suggested to play a critical function in the neurobiology of psychiatric disorders, including that related to neurodegenerative diseases. Prominently, epigenetic dysregulation currently brings considerable interest as an essential player in neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS) and drugs of abuse, including alcohol abuse disorder, where it may facilitate connections between genetic and environmental risk factors or directly influence disease-specific pathological factors. We have discussed the current state of histone methylation, therapeutic strategies, and future perspectives for these disorders. While not somatically heritable, the enzymes responsible for histone methylation regulation, such as histone methyltransferases and demethylases in neurons, are dynamic and reversible. They have become promising potential therapeutic targets to treat or prevent several neurodegenerative disorders. These findings, along with clinical data, may provide links between molecular-level changes and behavioral differences and provide novel avenues through which the epigenome may be targeted early on in people at risk for neurodegenerative disorders.     

Bismuth-induced effects on optical,lattice vibrational,and structural properties of bulk GaAsBi alloys

Bulk GaAs_{1 - x}Bi_x/GaAs alloys with various bismuth compositions are studied using power- and temperature-dependent photoluminescence (PL), Raman scattering, and atomic force microscopy (AFM). PL measurements exhibit that the bandgap of the alloy decreases with increasing bismuth composition. Moreover, PL peak energy and PL characteristic are found to be excitation intensity dependent. The PL signal is detectable below 150 K at low excitation intensities, but quenches at higher temperatures. As excitation intensity is increased, PL can be observable at room temperature and PL peak energy blueshifts. The quenching temperature of the PL signal tends to shift to higher temperatures with increasing bismuth composition, giving rise to an increase in Bi-related localization energy of disorders. The composition dependence of the PL is also found to be power dependent, changing from about 63 to 87 meV/Bi% as excitation intensity is increased. In addition, S-shaped temperature dependence at low excitation intensities is observed, a well-known signature of localized levels above valence band. Applying Varshni’s law to the temperature dependence of the PL peak energy, the concentration dependence of Debye temperature (β) and thermal expansion coefficient (α) are determined. AFM observations show that bismuth islands are randomly distributed on the surface and the diameter of the islands tends to increase with increasing bismuth composition. Raman scattering spectra show that incorporation of Bi into GaAs causes a new feature at around 185 cm^-1 with slightly increasing Raman intensity as the Bi concentration increases. A broad feature located between 210 and 250 cm^-1 is also observed and its intensity increases with increasing Bi content. Furthermore, the forbidden transverse optical (TO) mode becomes more pronounced for the samples with higher bismuth composition, which can be attributed to the effect of Bi-induced disorders on crystal symmetry.

PACS

78.55Cr 78.55-m 78.20-e 78.30-j     

Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease

Recent advances in next-generation sequencing (NGS) technologies have opened the door to a wellspring of information regarding the composition of the gut microbiota. Leveraging NGS technology, early metagenomic studies revealed that several diseases, such as Alzheimer’s disease, Parkinson’s disease, autism, and myalgic encephalomyelitis, are characterized by alterations in the diversity of gut-associated microbes. More recently, interest has shifted toward understanding how these microbes impact their host, with a special emphasis on their interactions with the brain. Such interactions typically occur either systemically, through the production of small molecules in the gut that are released into circulation, or through signaling via the vagus nerves which directly connect the enteric nervous system to the central nervous system. Collectively, this system of communication is now commonly referred to as the gut-microbiota-brain axis. While equally important, little attention has focused on the causes of the alterations in the composition of gut microbiota. Although several factors can contribute, mucosal immunity plays a significant role in shaping the microbiota in both healthy individuals and in association with several diseases. The purpose of this review is to provide a brief overview of the components of mucosal immunity that impact the gut microbiota and then discuss how altered immunological conditions may shape the gut microbiota and consequently affect neuroimmune diseases, using a select group of common neuroimmune diseases as examples.     

Efficacy of Sulforaphane in Neurodegenerative Diseases

Sulforaphane (SFN) is a phytocompound belonging to the isothiocyanate family. Although it was also found in seeds and mature plants, SFN is mainly present in sprouts of many cruciferous vegetables, including cabbage, broccoli, cauliflower, and Brussels sprouts. SFN is produced by the conversion of glucoraphanin through the enzyme myrosinase, which leads to the formation of this isothiocyanate. SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties, and for this reason, it aroused the interest of researchers. The aim of this review is to summarize the experimental studies present on Pubmed that report the efficacy of SFN in the treatment of neurodegenerative disease, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Therefore, thanks to its beneficial effects, SFN could be useful as a supplement to counteracting neurodegenerative diseases.     

Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases,and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)

Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015–2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.     

Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer’s Disease

The most common cause of dementia, especially in elderly people, is Alzheimer’s disease (AD), with aging as its main risk factor. AD is a multifactorial neurodegenerative disease. There are several factors increasing the risk of AD development. One of the main features of Alzheimer’s disease is impairment of brain energy. Hypometabolism caused by decreased glucose uptake is observed in specific areas of the AD-affected brain. Therefore, glucose hypometabolism and energy deficit are hallmarks of AD. There are several hypotheses that explain the role of glucose hypometabolism in AD, but data available on this subject are poor. Reduced transport of glucose into neurons may be related to decreased expression of glucose transporters in neurons and glia. On the other hand, glucose transporters may play a role as potential targets for the treatment of AD. Compounds such as antidiabetic drugs, agonists of SGLT1, insulin, siRNA and liposomes are suggested as therapeutics. Nevertheless, the suggested targets of therapy need further investigations.     

Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia

Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer’s disease (AD) and in Parkinson’s disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. Several experimental studies have shown that noradrenaline modulates neuroinflammation, mainly by acting on microglia/astrocytes function. In the present review, after a brief introduction on the anatomy and physiology of LC, we provide an overview of experimental data supporting a pathogenetic role of LC degeneration in AD and PD. Then, we describe in detail experimental data, obtained in vitro and in vivo in animal models, which support a potential role of neuroinflammation in such a link, and the specific molecules (i.e., released cytokines, glial receptors, including pattern recognition receptors and others) whose expression is altered by LC degeneration and might play a key role in AD/PD pathogenesis. New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients.     

Vibration-assisted upconversion of molecular luminescence induced by scanning tunneling microscopy

We investigate the effects of coupling between a molecular exciton, which consists of an electron and a hole in a molecule, and a surface plasmon (exciton-plasmon coupling) on the electron transitions of the molecule using nonequilibrium Green’s function method. Due to the exciton-plasmon coupling, excitation channels of the molecule arise in the energy range lower than the electronic excitation energy of the molecule. It is found that the electron transitions via these excitation channels give rise to the molecular luminescence and the vibrational excitations at the bias voltage lower than the electronic excitation energy of the molecule. Our results also indicate that the vibrational excitations assist the emission of photons, whose energy exceeds the product of the elementary charge and the bias voltage, (upconverted luminescence).     

Effect of cx-DHED on Abnormal Glucose Transporter Expression Induced by AD Pathologies in the 5xFAD Mouse Model

Alzheimer’s disease (AD) is a form of dementia associated with abnormal glucose metabolism resulting from amyloid-beta (Aβ) plaques and intracellular neurofibrillary tau protein tangles. In a previous study, we confirmed that carboxy-dehydroevodiamine∙HCl (cx-DHED), a derivative of DHED, was effective at improving cognitive impairment and reducing phosphorylated tau levels and synaptic loss in an AD mouse model. However, the specific mechanism of action of cx-DHED is unclear. In this study, we investigated how the cx-DHED attenuates AD pathologies in the 5xFAD mouse model, focusing particularly on abnormal glucose metabolism. We analyzed behavioral changes and AD pathologies in mice after intraperitoneal injection of cx-DHED for 2 months. As expected, cx-DHED reversed memory impairment and reduced Aβ plaques and astrocyte overexpression in the brains of 5xFAD mice. Interestingly, cx-DHED reversed the abnormal expression of glucose transporters in the brains of 5xFAD mice. In addition, otherwise low O-GlcNac levels increased, and the overactivity of phosphorylated GSK-3β decreased in the brains of cx-DHED-treated 5xFAD mice. Finally, the reduction in synaptic proteins was found to also improve by treatment with cx-DHED. Therefore, we specifically demonstrated the protective effects of cx-DHED against AD pathologies and suggest that cx-DHED may be a potential therapeutic drug for AD.     

Microbiota Alterations in Patients with Autoimmune Thyroid Diseases: A Systematic Review

Autoimmune thyroid diseases (AITDs) are chronic autoimmune disorders that cause impaired immunoregulation, leading to specific immune responses against thyroid antigens. Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are the major forms of AITDs. Increasing evidence suggests a possible role of microbiota alterations in the pathogenesis and progression of AITDs. This systematic review was designed to address the following question: “Is microbiota altered in patients with AITDs?” After screening the selected studies using the inclusion and exclusion criteria, 16 studies were included in this review (in accordance with PRISMA statement guidelines). A meta-analysis revealed that patients with HT showed significantly higher values of diversity indices (except for the Simpson index) and that patients with GD showed significant tendencies toward lower values of all assessed indices compared with healthy subjects. However, the latter demonstrated a higher relative abundance of Bacteroidetes and Actinobacteria at the phylum level and thus Prevotella and Bifidobacterium at the genus level, respectively. Thyroid peroxidase antibodies showed the most significant positive and negative correlations between bacterial levels and thyroid functional parameters. In conclusion, significant alterations in the diversity and composition of the intestinal microbiota were observed in both GD and HT patients.     

Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.     

AGEomics Biomarkers and Machine Learning—Realizing the Potential of Protein Glycation in Clinical Diagnostics

Protein damage by glycation, oxidation and nitration is a continuous process in the physiological system caused by reactive metabolites associated with dicarbonyl stress, oxidative stress and nitrative stress, respectively. The term AGEomics is defined as multiplexed quantitation of spontaneous modification of proteins damage and other usually low-level modifications associated with a change of structure and function—for example, citrullination and transglutamination. The method of quantitation is stable isotopic dilution analysis liquid chromatography—tandem mass spectrometry (LC-MS/MS). This provides robust quantitation of normal and damaged or modified amino acids concurrently. AGEomics biomarkers have been used in diagnostic algorithms using machine learning methods. In this review, I describe the utility of AGEomics biomarkers and provide evidence why these are close to the phenotype of a condition or disease compared to other metabolites and metabolomic approaches and how to train and test algorithms for clinical diagnostic and screening applications with high accuracy, sensitivity and specificity using machine learning approaches.