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Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Abstract The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain (E. coli BL21(DE3) ΔnlpI, ΔlpxM) was created for efficient OMV production, and OMVs were characterized using various methods. SpyCatcher was anchored to the OMV outer membrane using autotransporter-based surface display systems. Synthetic SpyTag-NODAGA conjugates were tested for OMV surface binding and 64Cu labeling efficiency. The final labeling protocol shows a radiochemical purity of 100% with a ~ 29% radiolabeling efficiency and excellent serum stability. The in vivo biodistribution of OMVs labeled with 64Cu was determined in mice using PET/MRI imaging which revealed that the biodistribution of radiolabeled OMVs in mice is characteristic of previously reported data with the highest organ uptakes corresponding to the liver and spleen 3, 6, and 12 h following intravenous administration. This novel method can serve as a basis for a general OMV radiolabeling scheme and could be used in vaccine- and drug-carrier development based on bioengineered OMVs.

Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including ultra-violet (UV) radiation, electron leakage during aerobic respiration, inflammatory responses mediated by macrophages, and other external stimuli or stress. The enhanced production of ROS is termed oxidative stress and this leads to cellular damage, such as protein carbonylation, lipid peroxidation, deoxyribonucleic acid (DNA) damage, and base modifications. This damage may manifest in various pathological states, including ageing, cancer, neurological diseases, and metabolic disorders like diabetes. On the other hand, the optimum levels of ROS have been implicated in the regulation of many important physiological processes. For example, the ROS generated in the mitochondria (mitochondrial ROS or mt-ROS), as a byproduct of the electron transport chain (ETC), participate in a plethora of physiological functions, which include ageing, cell growth, cell proliferation, and immune response and regulation. In this current review, we will focus on the mechanisms by which mt-ROS regulate different pathways of host immune responses in the context of infection by bacteria, protozoan parasites, viruses, and fungi. We will also discuss how these pathogens, in turn, modulate mt-ROS to evade host immunity. We will conclude by briefly giving an overview of the potential therapeutic approaches involving mt-ROS in infectious diseases.

Traumatic brain injury (TBI) is one of the most common causes of disability and mortality worldwide, creating a large socioeconomic burden annually. Secondary injury physiopathology is known to play a prominent role in exacerbating neurodegeneration post‐TBI and is potentially preventable by therapies. However, due to the heterogeneity of TBI and the complexity of the pathological mechanisms that ensue, there are currently no effective disease‐modifying treatments to prevent TBI‐associated disability and mortality. Nanotechnology has emerged in recent decades as a promising platform for the development of multifunctional neuroprotective agents for TBI. Herein, current multifunctional innovations are explored in this review in nanotechnology, which target the secondary injury pathological mechanisms of TBI and show promise in improving future post‐TBI management. Also, potential new directions for the future development of TBI treatment are discussed.

Following the in vivo biodistribution of platelets can contribute to a better understanding of their physiological and pathological roles, and nuclear imaging methods, such as single photon emission tomography (SPECT), provide an excellent method for that. SPECT imaging needs stable labeling of the platelets with a radioisotope. In this study, we report a new method to label platelets with 99mTc, the most frequently used isotope for SPECT in clinical applications. The proposed radiolabeling procedure uses a membrane-binding peptide, duramycin. Our results show that duramycin does not cause significant platelet activation, and radiolabeling can be carried out with a procedure utilizing a simple labeling step followed by a size-exclusion chromatography-based purification step. The in vivo application of the radiolabeled human platelets in mice yielded quantitative biodistribution images of the spleen and liver and no accumulation in the lungs. The performed small-animal SPECT/CT in vivo imaging investigations revealed good in vivo stability of the labeling, which paves the way for further applications of 99mTc-labeled-Duramycin in platelet imaging.

[This corrects the article DOI: 10.1371/journal.pone.0264554.].

The present study aimed to isolate and identify potential drugs from marine actinomycete Nocardiopsis exhalans and screen them for biomedical applications. The cell-free culture of N. exhalans was extracted with ethyl acetate and the solvent extract showed six fractions in thin-layer chromatography. The fractions were subjected to column chromatography for purification and evaluated for activity against human clinical pathogens. Fraction 4 showed significant activity and was identified as N-(2-hydroxyphenyl)-2-phenazinamine (NHP) using spectral analyses. Further, NHP showed excellent biofilm inhibitory activity against human clinical pathogens Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The in vitro antioxidant activity confirmed that NHP is scavenging the oxidative stress-enhancing molecules. The anti-proliferative activity of NHP against human breast cancer cells showed significant activity at 300 µg/ml and less cytotoxic activity against normal cells. Additionally, the toxicity assessment against zebrafish revealed that NHP does not cause any toxicity in the important organs. The results highlight N. exhalans as a promising candidate for the development of antibiotics with potential therapeutic applications.

Functional metal nanomaterials, especially in the nanocluster (NC) size regime, with strong fluorescence, aqueous colloidal stability, and low toxicity, necessitate their application potential in biology and environmental science. Here, we successfully report a simple cost-effective method for red-/green-color-emitting protein/amino-acid-mediated Cu NCs in an aqueous medium. As-synthesized Cu NCs were characterized through UV-Vis absorption spectroscopy, fluorescence spectroscopy, time-resolved photoluminescence, dynamic light scattering, zeta potential, transmission electron microscopy and X-ray photoelectron spectroscopy. The optical properties of both Cu NCs responded linearly to the variation in pH in the neutral and alkaline ranges, and a robust pH reversible nature (between pH 7 and 11) was observed that could be extended to rapid, localized pH sensor development. However, a contrasting pH response nature between protein–Cu NCs and amino acid–Cu NCs was recorded. The alteration in protein secondary structure and strong binding nature of the surfactants were suggested to explain this behavior. Furthermore, we investigated their use as an efficient optical probe for fluoride ion detection. The limit of detection for protein–Cu NCs is 6.74 µM, whereas the limit of detection for amino acid–Cu NCs is 4.67 µM. Thus, it is anticipated that ultrasmall Cu NCs will exhibit promise in biological and environmental sensing applications.

Abstract Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson’s disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes to PD pathogenesis; specifically, the studies that have examined VPS35 thus far have differed in results and methodologies. We generated a VPS35 D620N mouse model using a Rosa26-based transgene expression platform to allow expression in a spatial manner, so as to better address these discrepancies. Here, aged (20-months-old) mice were first subjected to behavioral tests. Subsequently, DAB staining analysis of substantia nigra (SN) dopaminergic neurons with the marker for tyrosine hydroxylase (TH) was performed. Next, HPLC was used to determine dopamine levels, along with levels of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum. Western blotting was also performed to study the levels of key proteins associated with PD. Lastly, autoradiography (ARG) evaluation of [3H]FE-PE2I binding to the striatal dopamine transporter DAT was carried out. We found that VPS35 D620N Tg mice displayed a significantly higher dopamine level than NTg counterparts. All results were then compared with that of current VPS35 studies to shed light on the disease pathogenesis. Our model allows future studies to explicitly control spatial expression of the transgene which would generate a more reliable PD phenotype.

The aim of this study was to develop and characterize a Prussian Blue based biocompatible and chemically stable T1 magnetic resonance imaging (MRI) contrast agent with near infrared (NIR) optical contrast for preclinical application. The physical properties of the Prussian blue nanoparticles (PBNPs) (iron (II); iron (III);octadecacyanide) were characterized with dynamic light scattering (DLS), zeta potential measurement, atomic force microscopy (AFM), and transmission electron microscopy (TEM). In vitro contrast enhancement properties of PBNPs were determined by MRI. In vivo T1-weighted contrast of the prepared PBNPs was investigated by MRI and optical imaging modality after intravenous administration into NMRI-Foxn1 nu/nu mice. The biodistribution studies showed the presence of PBNPs predominantly in the cardiovascular system. Briefly, in this paper we show a novel approach for the synthesis of PBNPs with enhanced iron content for T1 MRI contrast. This newly synthetized PBNP platform could lead to a new diagnostic agent, replacing the currently used Gadolinium based substances.

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders that is implicated in aging populations. As numerous developed nations are experiencing progressively aging populations today, there is a heightened propensity for the occurrence of PD cases. Alpha-synuclein (α-syn) aggregation has been considered to be the pivotal mechanism leading to PD pathogenesis. Thus, early diagnostic and therapeutic strategies targeting the misfolded α-syn protein can potentially improve the prognosis of PD. With rapid advancements in nanotechnology in the last decade, effective solutions to various neurodegenerative and oncological diseases have been suggested. This review will explore the current innovations in nanotechnology that target the α-syn aggregation pathway, and reinstate the promise they hold as effective early diagnostic and therapeutic solutions to PD.

Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.

The aqueous extract of Alternanthera sessilis (As) acts as the precursors for the quick reduction of silver ions, which leads to the formation of silver nanoparticles. In the agar, well diffusion method of the Klebsiella pneumoniae shows the minimal inhibitory concentration of 12 mm against A. sessilis mediated silver nanoparticles (As-AgNPs) at 60 µg/mL concentration. Fabric treated with novel AS-AgNPs is tested against the K. pneumoniae and shows an inhibitory action of 12 mm with mixed cotton that determines the antimicrobial efficacy of the fabrics. Uv- visible spectrophotometer was performed, showing a surface plasmon resonance peak at 450 nm cm−1. FTIR shows the vibration and the infrared radiation at a specific wavelength of 500–4000 cm−1. The HR-TEM analysis showed the presence of black-white crystalline, spherical-shaped As-AgNPs embedded on the fabrics range of 15 nm–40 nm. In the scanning electron microscope, the presence of small ball-shaped As-AgNPs embedded on the fabrics at a voltage of 30 KV was found with a magnification of 578X. EDAX was performed in which the nanoparticles show a peak of 2.6–3.9 KeV, and it also reveals the presence of the composition, distribution, and elemental mapping of the nanoparticles. The cytotoxic activity of synthesized nanosilver was carried out against L929 cell lines, which show cell viability at a concentration of 2.5 µg mL−1. Cell proliferation assay shows no cytotoxicity against L929 cell lines for 24 h. In this study, the green synthesis of silver nanoparticles from A. sessilis appears to be a cheap, eco-friendly, and alternative approach for curing infectious ulcers on the floor of the stratum corneum. Nanotechnology conjoined with herbal therapeutics provides a promising solution for wound management.

Magnetoencephalography (MEG) plays a pivotal role in the diagnosis of brain disorders. In this review, we have investigated potential MEG applications for analysing brain disorders. The signal-to-noise ratio (SNRMEG = 2.2 db, SNREEG < 1 db) and spatial resolution (SRMEG = 2–3 mm, SREEG = 7–10 mm) is higher for MEG than EEG, thus MEG potentially facilitates accurate monitoring of cortical activity. We found that the direct electrophysiological MEG signals reflected the physiological status of neurological disorders and play a vital role in disease diagnosis. Single-channel connectivity, as well as brain network analysis, using MEG data acquired during resting state and a given task has been used for the diagnosis of neurological disorders such as epilepsy, Alzheimer’s, Parkinsonism, autism, and schizophrenia. The workflow of MEG and its potential applications in the diagnosis of disease and therapeutic planning are also discussed. We forecast that computer-aided algorithms will play a prominent role in the diagnosis and prediction of neurological diseases in the future. The outcome of this narrative review will aid researchers to utilise MEG in diagnostics.

Bacterial extracellular proteins participate in the host cell communication by virtue of the modulation of pathogenicity, commensalism and mutualism. Studies on the microbiome of cervical mucus of the water buffalo (Bubalus bubalis) have shown the occurrence of Staphylococcus pasteuri and that the presence of this bacterium is indicative of various physiological and reproductive states in the host. Recently, S. pasteuri has been isolated from the cervical mucus of the buffalo during the different phases of estrous cycle, and has proved to be much more pronounced during the estrus phase. The basis underlying the availability of a significantly increased S. pasteuri population, specifically during the estrus phase, is not known. Consequently, it is important to determine the significance of the specific abundance of S. pasteuri during the estrus phase of the buffalo host, particularly from the perspective of whether this bacterial species is capable of contributing to sexual communication via its extracellular proteins and volatiles. Therefore, the relevance of S. pasteuri exoproteome in the buffalo cervical mucus during the estrus phase was analyzed using LC-MS/MS. As many as 219 proteins were identified, among which elongation factor Tu (EF-Tu), 60-kDa chaperonin (Cpn60), enolase, fructose-bisphosphate aldolase class 1 (FBP aldolase), enoyl-[acyl-carrier-protein] reductase [NADPH] (ENR) and lipoprotein (Lpp) were the functionally important candidates. Most of the proteins present in the exoproteome of S. pasteuri were those involved in cellular–metabolic functions, as well as catalytic- and binding activities. Moreover, computational studies of Lpp have shown enhanced interaction with volatiles such as acetic-, butanoic-, isovaleric- and valeric acids, which were identified in the cervical mucus S. pasteuri culture supernatant. The present findings suggest that S. pasteuri extracellular proteins may play an important role in buffalo sexual communication during the estrus phase.

A rapid and one-pot synthesis of poly 3-thiopheneacetic acid (PTAA) functionalized polyurea polymer dots (Pdots) using polyethyleneimine and isophorone diisocyanate is reported. The one-pot mini-emulsion polymerization technique yielded Pdots with an average diameter of ~20 nm. The size, shape, and concentration of the surface functional groups could be controlled by altering the synthesis parameters such as ultrasonication time, concentration of the surfactant, and crosslinking agent, and the types of isocyanates utilized for the synthesis. Colloidal properties of Pdots were characterized using dynamic light scattering and zeta potential measurements. The spherical geometry of Pdots was confirmed by scanning electron microscopy. The Pdots were post-functionalized by 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid for chelating gadolinium nanoparticles (Gd3+) that provide magnetic properties to the Pdots. Thus, the synthesized Pdots possess fluorescent and magnetic properties, imparted by PTAA and Gd3+, respectively. Fluorescence spectroscopy and microscopy revealed that the synthesized dual-functional Gd3+-Pdots exhibited detectable fluorescent signals even at lower concentrations. Magnetic levitation experiments indicated that the Gd3+-Pdots could be easily manipulated via an external magnetic field. These findings illustrate that the dua- functional Gd3+-Pdots could be potentially utilized as fluorescent reporters that can be magnetically manipulated for bioimaging applications.

Nanoclusters possess an ultrasmall size, amongst other favorable attributes, such as a high fluorescence and long-term colloidal stability, and consequently, they carry several advantages when applied in biological systems for use in diagnosis and therapy. Particularly, the early diagnosis of diseases may be facilitated by the right combination of bioimaging modalities and suitable probes. Amongst several metallic nanoclusters, copper nanoclusters (Cu NCs) present advantages over gold or silver NCs, owing to their several advantages, such as high yield, raw abundance, low cost, and presence as an important trace element in biological systems. Additionally, their usage in diagnostics and therapeutic modalities is emerging. As a result, the fluorescent properties of Cu NCs are exploited for use in optical imaging technology, which is the most commonly used research tool in the field of biomedicine. Optical imaging technology presents a myriad of advantages over other bioimaging technologies, which are discussed in this review, and has a promising future, particularly in early cancer diagnosis and imaging-guided treatment. Furthermore, we have consolidated, to the best of our knowledge, the recent trends and applications of copper nanoclusters (Cu NCs), a class of metal nanoclusters that have been gaining much traction as ideal bioimaging probes, in this review. The potential modes in which the Cu NCs are used for bioimaging purposes (e.g., as a fluorescence, magnetic resonance imaging (MRI), two-photon imaging probe) are firstly delineated, followed by their applications as biosensors and bioimaging probes, with a focus on disease detection.

Doxorubicin is an extensively prescribed antineoplastic agent. It is also known for adverse effects, among which cardiotoxicity tops the list. The possible mechanism underlying doxorubicin (DOX)-mediated cardiotoxicity has been investigated in this study. Further, to reduce the DOX-mediated cardiotoxicity, DOX was conjugated with Chitosan Nanoparticles (DCNPs) and supplemented with propionic acid. Initially, the drug loading efficacy and conjugation of DOX with chitosan was confirmed by UV–Visible Spectroscopy (UV) and Fourier Transform Infrared Spectroscopy (FTIR). The average sizes of the synthesized Chitosan Nanoparticles (CNPs) and DCNPs were measured by Dynamic Light Scattering (DLS) analysis as 187.9 ± 1.05 nm and 277.3 ± 8.15 nm, respectively, and the zeta potential values were recorded as 55.2 ± 0.7 mV and 51.9 ± 1.0 mV, respectively. The size and shape of CNPs and DCNPs were recorded using a High-Resolution Electron Microscopy (HRTEM). The particles measured

Abstract With primitive approaches, the diagnosis and therapy were operated at the cellular, molecular, or even at the genetic level. As the diagnostic techniques are more concentrated towards molecular level, multi modal imaging becomes specifically essential. Multi-modal imaging has extensive applications in clinical as well as in pre-clinical studies. Positron Emission Tomography (PET) has flourished in the field of nuclear medicine, which has motivated it to fuse with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) for PET/CT and PET/MRI respectively. However, the challenges in PET/CT are due to the inability of simultaneous acquisition and reduced soft tissue contrast, which has led to the development of PET/MRI. Also, MRI offers the better soft tissue contrast over CT. Hence, fusion of PET and MRI results in combining structural information with functional image from PET. Yet, it has many technical challenges due to the interference between the modalities. Also, it must be resolved with various approaches for addressing the shortcomings of each system and improvise on the image quantification system. This review elaborates on the various challenges in the present PET/MRI system and the future directions of the hybrid modality. Also, the different data acquisition and analysis techniques of PET/MRI system are discussed with enhanced details on the software tools.

This study reports the synthesis of silver nanoparticles using amino acid L-histidine as a reducing and capping agent as an eco-friendly approach. Fabricated L-histidine-capped silver nanoparticles (L-HAgNPs) were characterized by spectroscopic and microscopic studies. Spherical shaped L-HAgNPs were synthesized with a particle size of 47.43 ± 19.83 nm and zeta potential of −20.5 ± 0.95 mV. Results of the anticancer potential of L-HAgNPs showed antiproliferative effect against SiHa cells in a dose-dependent manner with an IC50 value of 18.25 ± 0.36 µg/mL. Fluorescent microscopic analysis revealed L-HAgNPs induced reactive oxygen species (ROS) mediated mitochondrial dysfunction, leading to activation of apoptotic pathway and DNA damage eventually causing cell death. To conclude, L-HAgNPs can act as promising candidates for cervical cancer therapy.

Functional Near-Infrared Spectroscopy (fNIRS) is a wearable optical spectroscopy system originally developed for continuous and non-invasive monitoring of brain function by measuring blood oxygen concentration. Recent advancements in brain–computer interfacing allow us to control the neuron function of the brain by combining it with fNIRS to regulate cognitive function. In this review manuscript, we provide information regarding current advancement in fNIRS and how it provides advantages in developing brain–computer interfacing to enable neuron function. We also briefly discuss about how we can use this technology for further applications.

Amyloid-β (Aβ) is a dynamic peptide of Alzheimer’s disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by β- and γ-secretases and engenders the Aβ. In addition, externally produced Aβ gets inside the cells by receptors mediated internalization. An elevated amount of Aβ yields spontaneous aggregation which causes organelles impairment. Aβ stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. Aβ travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. Aβ disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, Aβ precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, Aβ act as a transcription regulator as well as inhibits telomerase activity. Both Aβ and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the Aβ mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.

This review is extensively focused on the enhancement of cognitive functions while performing physical exercises categorized into cardiovascular exercises, resistance training, martial arts, racquet sports, dancing and mind-body exercises. Imaging modalities, viz. functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), have been included in this review. This review indicates that differences are present in cognitive functioning while changing the type of physical activity performed. This study concludes that employing fNIRS helps overcome certain limitations of fMRI. Further, the effects of physical activity on a diverse variety of the population, from active children to the old people, are discussed.

The development of a biomimetic neuronal network from neural cells is a big challenge for researchers. Recent advances in nanotechnology, on the other hand, have enabled unprecedented tools and techniques for guiding and directing neural stem cell proliferation and differentiation in vitro to construct an in vivo-like neuronal network. Nanotechnology allows control over neural stem cells by means of scaffolds that guide neurons to reform synaptic networks in suitable directions in 3D architecture, surface modification/nanopatterning to decide cell fate and stimulate/record signals from neurons to find out the relationships between neuronal circuit connectivity and their pathophysiological functions. Overall, nanotechnology-mediated methods facilitate precise physiochemical controls essential to develop tools appropriate for applications in neuroscience. This review emphasizes the newest applications of nanotechnology for examining central nervous system (CNS) roles and, therefore, provides an insight into how these technologies can be tested in vitro before being used in preclinical and clinical research and their potential role in regenerative medicine and tissue engineering.

The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. Numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. The virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. Neurophysiological recordings together with virtual stimulations can assist in correlating humans’ physiological perception with response in the environment designed virtually. The effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. Moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. Challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal signals. This article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

The rapid advancements in machine learning, graphics processing technologies and the availability of medical imaging data have led to a rapid increase in the use of deep learning models in the medical domain. This was exacerbated by the rapid advancements in convolutional neural network (CNN) based architectures, which were adopted by the medical imaging community to assist clinicians in disease diagnosis. Since the grand success of AlexNet in 2012, CNNs have been increasingly used in medical image analysis to improve the efficiency of human clinicians. In recent years, three-dimensional (3D) CNNs have been employed for the analysis of medical images. In this paper, we trace the history of how the 3D CNN was developed from its machine learning roots, we provide a brief mathematical description of 3D CNN and provide the preprocessing steps required for medical images before feeding them to 3D CNNs. We review the significant research in the field of 3D medical imaging analysis using 3D CNNs (and its variants) in different medical areas such as classification, segmentation, detection and localization. We conclude by discussing the challenges associated with the use of 3D CNNs in the medical imaging domain (and the use of deep learning models in general) and possible future trends in the field.

(1) Background. The main goal of this work was to develop a fluorescent dye-labelling technique for our previously described nanosized platform, citrate-coated Prussian blue (PB) nanoparticles (PBNPs). In addition, characteristics and stability of the PB nanoparticles labelled with fluorescent dyes were determined. (2) Methods. We adsorbed the fluorescent dyes Eosin Y and Rhodamine B and methylene blue (MB) to PB-nanoparticle systems. The physicochemical properties of these fluorescent dye-labeled PBNPs (iron(II);iron(III);octadecacyanide) were determined using atomic force microscopy, dynamic light scattering, zeta potential measurements, scanning- and transmission electron microscopy, X-ray diffraction, and Fourier-transformation infrared spectroscopy. A methylene-blue (MB) labelled, polyethylene-glycol stabilized PBNP platform was selected for further assessment of in vivo distribution and fluorescent imaging after intravenous administration in mice. (3) Results. The MB-labelled particles emitted a strong fluorescent signal at 662 nm. We found that the fluorescent light emission and steric stabilization made this PBNP-MB particle platform applicable for in vivo optical imaging. (4) Conclusion. We successfully produced a fluorescent and stable, Prussian blue-based nanosystem. The particles can be used as a platform for imaging contrast enhancement. In vivo stability and biodistribution studies revealed new aspects of the use of PBNPs.

Lanthanide-doped upconversion-luminescent nanoparticles (UCNPs), which can be excited by near-infrared (NIR) laser irradiation to emit multiplex light, have been proven to be very useful for in vitro and in vivo molecular imaging studies. In comparison with the conventionally used down-conversion fluorescence imaging strategies, the NIR light excited luminescence of UCNPs displays high photostability, low cytotoxicity, little background auto-fluorescence, which allows for deep tissue penetration, making them attractive as contrast agents for biomedical imaging applications. In this review, we will mainly focus on the latest development of a new type of lanthanide-doped UCNP material and its main applications for in vitro and in vivo molecular imaging and we will also discuss the challenges and future perspectives.