Non-invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by H magnetic resonance spectroscopy.

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D.

Non-rigid-registration-based positioning and labelling of triaxial OPMs on a flexible cap for wearable magnetoencephalography.

Background: Recent advances in highly sensitive miniaturized optically pumped magnetometers (OPMs) have enabled the development of wearable magnetoencephalography (MEG) offering great flexibility in experimental setting. The OPM array for wearable MEG is typically attached to a flexible cap and exhibits a variable spatial layout across different subjects, which imposes challenges concerning the efficient positioning and labelling of OPMs.

New Method: A pair of reflective markers are affixed to each triaxial OPM sensor above its cable to determine its location and sensitive axes.

Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations.

The hypocretin (Hcrt) (also known as orexin) neuropeptidic wakefulness-promoting system is implicated in the regulation of spatial memory, but its specific role and mechanisms remain poorly understood. In this study, we revealed the innervation of the medial entorhinal cortex (MEC) by Hcrt neurons in mice. Using the genetically encoded G-protein-coupled receptor activation-based Hcrt sensor, we observed a significant increase in Hcrt levels in the MEC during novel object-place exploration.

Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples.

Carboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids.

Physical Contacts Between Mitochondria and WPBs Participate in WPB Maturation.

Background: Weibel-Palade bodies (WPBs) are endothelial cell-specific cigar-shaped secretory organelles containing various biologically active molecules. WPBs play crucial roles in thrombosis, hemostasis, angiogenesis, and inflammation. The main content of WPBs is the procoagulant protein vWF (von Willebrand factor).

Pediatric Neural Changes to Physical and Emotional Pain After Intensive Interdisciplinary Pain Treatment: A Pilot Study.

Brain areas activated during pain can contribute to enhancing or reducing the pain experience, showing a potential connection between chronic pain and the neural response to pain in adolescents and youth. This study examined changes in brain activation associated with experiencing physical pain, and the observation of physical and emotional pain in others, by using functional magnetic resonance imaging (fMRI) before and after intensive interdisciplinary pain treatment (IIPT). Eighteen youth (age 14 to 18) with widespread chronic pain completed fMRI testing before and after IIPT to assess changes in brain activation in response to physical and emotional pain.

Force opens a monomeric channel pore.

In this issue of Neuron, Zheng et al. report the monomeric architecture of mechanosensitive ion channels TMEM63A and TMEM63B. They show that these high-threshold channels function as monomers on the plasma membrane.

Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

Background: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms.

Alzheimer's disease cortical morphological phenotypes are associated with TOMM40'523-APOE haplotypes.

Both the APOE ε4 and TOMM40 rs10524523 ("523") genes have been associated with risk for Alzheimer's disease (AD) and neuroimaging biomarkers of AD. No studies have investigated the relationship of TOMM40'523-APOE ε4 on the structural complexity of the brain in AD individuals. We quantified brain morphology and multiple cortical attributes in individuals with mild cognitive impairment (MCI) and AD, then tested whether APOE ε4 or TOMM40 poly-T genotypes were related to AD morphological biomarkers in cognitively unimpaired (CU) and MCI/AD individuals.

Enhancing Structural and Thermal Properties of Poly(lactic acid) Using Graphene Oxide Filler and Anionic Surfactant Treatment.

Graphene has attracted extensive attention in various fields due to its intriguing properties. In this work, nanocomposite films based on poly(lactic acid) (PLA and PLLA) polymers filled with graphene oxide (GO) were developed. The impact of treating GO with the anionic surfactant dioctyl sulfosuccinate sodium salt (AOT) on the properties of the resulting nanocomposites was investigated.

EEG-based auditory attention decoding with audiovisual speech for hearing-impaired listeners.

Auditory attention decoding (AAD) was used to determine the attended speaker during an auditory selective attention task. However, the auditory factors modulating AAD remained unclear for hearing-impaired (HI) listeners. In this study, scalp electroencephalogram (EEG) was recorded with an auditory selective attention paradigm, in which HI listeners were instructed to attend one of the two simultaneous speech streams with or without congruent visual input (articulation movements), and at a high or low target-to-masker ratio (TMR).

Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).

Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear.

Stimulating learning: A functional MRI and behavioral investigation of the effects of transcranial direct current stimulation on stochastic learning in schizophrenia.

Transcranial direct current stimulation (tDCS) of the medial prefrontal cortex (mPFC) is under clinical investigation as a treatment for cognitive deficits. We investigate the effects of tDCS over the mPFC on performance SSLT in individuals with schizophrenia, and the underlying neurophysiological effect in regions associated with learning values and stimulus-outcome relationships. In this parallel-design double-blind pilot study, 49 individuals with schizophrenia, of whom 28 completed a fMRI, were randomized into active or sham tDCS stimulation groups.

Leveraging 3D Bioprinting and Photon-Counting Computed Tomography to Enable Noninvasive Quantitative Tracking of Multifunctional Tissue Engineered Constructs.

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon-counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom-engineer scaffolds with traceability.

Precise Detection, Control and Synthesis of Chiral Compounds at Single-Molecule Resolution.

Chirality, as the symmetric breaking of molecules, plays an essential role in physical, chemical and especially biological processes, which highlights the accurate distinction among heterochiralities as well as the precise preparation for homochirality. To this end, the well-designed structure-specific recognizer and catalysis reactor are necessitated, respectively. However, each kind of target molecules requires a custom-made chiral partner and the dynamic disorder of spatial-orientation distribution of molecules at the ensemble level leads to an inefficient protocol.

Improved dual-color GRAB sensors for monitoring dopaminergic activity .

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation-based DA (GRAB) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations.

Miniature Two-Photon Microscopic Imaging Using Dielectric Metalens.

Miniature two-photon microscopy has emerged as a powerful technique for investigating brain activity in freely moving animals. Ongoing research objectives include reducing probe weight and minimizing animal behavior constraints caused by probe attachment. Employing dielectric metalenses, which enable the use of sizable optical components in flat device structures while maintaining imaging resolution, is a promising solution for addressing these challenges.

Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level.

Positron Emission Tomography Quantitative Assessment of Off-Target Whole-Body Biodistribution of I-124-Labeled Adeno-Associated Virus Capsids Administered to Cerebral Spinal Fluid.

Based on studies in experimental animals demonstrating that administration of adeno-associated virus (AAV) vectors to the cerebrospinal fluid (CSF) is an effective route to transfer genes to the nervous system, there are increasing number of clinical trials using the CSF route to treat nervous system disorders. With the knowledge that the CSF turns over four to five times daily, and evidence in experimental animals that at least some of CSF administered AAV vectors are distributed to systemic organs, we asked: with AAV administration to the CSF, what fraction of the total dose remains in the nervous system and what fraction goes off target and is delivered systemically? To quantify the biodistribution of AAV capsids immediately after administration, we covalently labeled AAV capsids with iodine 124 (I-124), a cyclotron generated positron emitter, enabling quantitative positron emission tomography scanning of capsid distribution for up to 96 h after AAV vector administration. We assessed the biodistribution to nonhuman primates of I-124-labeled capsids from different AAV clades, including 9 (clade F), rh.

An artificial intelligence-based pipeline for automated detection and localisation of epileptic sources from magnetoencephalography.

Magnetoencephalography (MEG) is a powerful non-invasive diagnostic modality for presurgical epilepsy evaluation. However, the clinical utility of MEG mapping for localising epileptic foci is limited by its low efficiency, high labour requirements, and considerable interoperator variability. To address these obstacles, we proposed a novel artificial intelligence-based automated magnetic source imaging (AMSI) pipeline for automated detection and localisation of epileptic sources from MEG data.

Predicting ischemic stroke risk from atrial fibrillation based on multi-spectral fundus images using deep learning.

Background: Ischemic stroke (IS) is one of the most common serious secondary diseases of atrial fibrillation (AF) within 1 year after its occurrence, both of which have manifestations of ischemia and hypoxia of the small vessels in the early phase of the condition. The fundus is a collection of capillaries, while the retina responds differently to light of different wavelengths. Predicting the risk of IS occurring secondary to AF, based on subtle differences in fundus images of different wavelengths, is yet to be explored.

WarpPINN: Cine-MR image registration with physics-informed neural networks.

The diagnosis of heart failure usually includes a global functional assessment, such as ejection fraction measured by magnetic resonance imaging. However, these metrics have low discriminate power to distinguish different cardiomyopathies, which may not affect the global function of the heart. Quantifying local deformations in the form of cardiac strain can provide helpful information, but it remains a challenge.

Orange/far-red hybrid voltage indicators with reduced phototoxicity enable reliable long-term imaging in neurons and cardiomyocytes.

Hybrid voltage indicators (HVIs) are chemogenetic sensors that combines the superior photophysical properties of organic dyes and the genetic targetability of protein sensors to report transient membrane voltage changes. They exhibit boosted sensitivity in excitable cells such as neurons and cardiomyocytes. However, the voltage signals recorded during long-term imaging are severely diminished or distorted due to phototoxicity and photobleaching issues.