The ergodicity question when imaging DNA conformation using liquid cell electron microscopy.

Assessing the ergodicity of graphene liquid cell electron microscope measurements, we report that loop states of circular DNA interconvert reversibly and that loop numbers follow the Boltzmann distribution expected for this molecule in bulk solution, provided that the electron dose is low (80-keV electron energy and electron dose rate 1-20 e Å s). This imaging technique appears to act as a "slow motion" camera that reveals equilibrated distributions by imaging the time average of a few molecules without the need to image a spatial ensemble.

Metabolic syndrome and adiposity: Risk factors for decreased myelin in cognitively healthy adults.

Metabolic syndrome (MetS) is a cluster of conditions that affects ∼25% of the global population, including excess adiposity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is one of major risk factors not only for chronic diseases, but also for dementia and cognitive dysfunction, although the underlying mechanisms remain poorly understood. White matter is of particular interest in the context of MetS due to the metabolic vulnerability of myelin maintenance, and the accumulating evidence for the importance of the white matter in the pathophysiology of dementia.

Imaging microglia surveillance during sleep-wake cycles in freely behaving mice.

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice.

Increases in anterograde axoplasmic transport in neurons of the hyper-glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport.

The excitatory neurotransmitter glutamate has a role in neuronal migration and process elongation in the central nervous system (CNS). The effects of chronic glutamate hyperactivity on vesicular and protein transport within CNS neurons, that is, processes necessary for neurite growth, have not been examined previously. In this study, we measured the effects of lifelong hyperactivity of glutamate neurotransmission on axoplasmic transport in CNS neurons.

Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study.

Background: Cerliponase alfa is a recombinant human tripeptidyl peptidase 1 (TPP1) enzyme replacement therapy for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), which is caused by mutations in the TPP1 gene. We aimed to determine the long-term safety and efficacy of intracerebroventricular cerliponase alfa in children with CLN2 disease.

Methods: This analysis includes cumulative data from a primary 48-week, single-arm, open-label, multicentre, dose-escalation study (NCT01907087) and the 240-week open-label extension with 6-month safety follow-up, conducted at five hospitals in Germany, Italy, the UK, and the USA.

Functional dissection of KATP channel structures reveals the importance of a conserved interface.

ATP-sensitive potassium channels (KATP) are inhibited by ATP but activated by Mg-ADP, coupling the intracellular ATP/ADP ratio to the potassium conductance of the plasma membrane. Although there has been progress in determining the structure of KATP, the functional significance of the domain-domain interface in the gating properties of KATP channels remains incompletely understood. In this study, we define the structure of KATP as two modules: KATP and SUR.

Quantitatively mapping local quality of super-resolution microscopy by rolling Fourier ring correlation.

In fluorescence microscopy, computational algorithms have been developed to suppress noise, enhance contrast, and even enable super-resolution (SR). However, the local quality of the images may vary on multiple scales, and these differences can lead to misconceptions. Current mapping methods fail to finely estimate the local quality, challenging to associate the SR scale content.

Reconfigurable moiré nanolaser arrays with phase synchronization.

Miniaturized lasers play a central role in the infrastructure of modern information society. The breakthrough in laser miniaturization beyond the wavelength scale has opened up new opportunities for a wide range of applications, as well as for investigating light-matter interactions in extreme-optical-field localization and lasing-mode engineering. An ultimate objective of microscale laser research is to develop reconfigurable coherent nanolaser arrays that can simultaneously enhance information capacity and functionality.

Structural characterization of solvent-based food preparation of jellyfish.

Jellyfish as a potential sustainable food material has recently gained increasing interest. However, with their soft gel-like texture and easy spoilage, it remains challenging to achieve desirable edible structures from jellyfish. The culinary preparation of jellyfish is a complex process and extends beyond conventional cooking methods.

Brain connectivity and academic skills in English learners.

English learners (ELs) are a rapidly growing population in schools in the United States with limited experience and proficiency in English. To better understand the path for EL's academic success in school, it is important to understand how EL's brain systems are used for academic learning in English. We studied, in a cohort of Hispanic middle-schoolers (n = 45, 22F) with limited English proficiency and a wide range of reading and math abilities, brain network properties related to academic abilities.

Impact of Parathyroidectomy Versus Oral Cinacalcet on Bone Mineral Density in Patients on Peritoneal Dialysis With Advanced Secondary Hyperparathyroidism: The PROCEED Pilot Randomized Trial.

Rationale & Objective: Parathyroidectomy and calcimimetics have been used to reduce fracture risk in patients with kidney failure and advanced secondary hyperparathyroidism (SHPT), but direct comparisons of these treatment approaches have not been implemented. This pilot study compared their effects on bone mineral density (BMD) in this patient population.

Study Design: A prospective pilot open-label randomized trial.

Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo.

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

Race and sex differences in the association between lifespan glycemic status and midlife cognitive function: the Bogalusa heart study.

Introduction: Glycemic markers throughout life are associated with increased risk of midlife cognitive decline, yet it is unclear whether these associations differ by race and sex.

Methods: This study used cross-sectional analysis of prospectively maintained cohort. 1,295 participants in the Bogalusa Heart Study, a biracial epidemiological cohort located in a micropolitan area core setting, provided fasting plasma insulin (FPI) and glucose (FPG) biannually from 1973 to 2016.

Broadband transparent ultrasound transducer with polymethyl methacrylate as matching layer for photoacoustic microscopy.

Photoacoustic imaging (PAI) uniquely combines optics and ultrasound, presenting a promising role in biomedical imaging as a non-invasive and label-free imaging technology. As the traditional opaque ultrasound (US) transducers could hinder the transportation of the excitation light and limit the performance of PAI system, piezoelectric transparent ultrasonic transducers (TUTs) with indium tin oxide (ITO) electrodes have been developed to allow light transmission through the transducer and illuminate the sample directly. Nevertheless, without having transparent matching materials with appropriate properties, the bandwidth of those TUTs was generally narrow.

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series.

Despite being a major cause of preventable death worldwide, alcohol use disorder (AUD) currently has only 3 FDA-approved pharmacotherapies. The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide has shown promise in preclinical studies for reducing alcohol consumption, but there are currently no randomized clinical trials that associate a decline in AUD symptoms with semaglutide use. This case series presents 6 patients with positive AUD screenings who were treated with semaglutide for weight loss.

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

Background: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities.

The role of halogens in Au-S bond cleavage for energy-differentiated catalysis at the single-bond limit.

The transformation from one compound to another involves the breaking and formation of chemical bonds at the single-bond level, especially during catalytic reactions that are of great significance in broad fields such as energy conversion, environmental science, life science and chemical synthesis. The study of the reaction process at the single-bond limit is the key to understanding the catalytic reaction mechanism and further rationally designing catalysts. Here, we develop a method to monitor the catalytic process from the perspective of the single-bond energy using high-resolution scanning tunneling microscopy single-molecule junctions.

Structural insights into the assembly and mechanism of mpox virus DNA polymerase complex F8-A22-E4-H5.

The DNA replication of mpox virus is performed by the viral polymerase F8 and also requires other viral factors, including processivity factor A22, uracil DNA glycosylase E4, and phosphoprotein H5. However, the molecular roles of these viral factors remain unclear. Here, we characterize the structures of F8-A22-E4 and F8-A22-E4-H5 complexes in the presence of different primer-template DNA substrates.

Probing Renal Microstructure and Function with Advanced Diffusion MRI: Concepts, Applications, Challenges, and Future Directions.

Diffusion measurements in the kidney are affected not only by renal microstructure but also by physiological processes (i.e., glomerular filtration, water reabsorption, and urine formation).

Successful treatment of binge eating disorder with the GLP-1 agonist semaglutide: A retrospective cohort study.

Objective: Binge eating disorder (BED) is the most common eating disorder, and yet only one pharmacotherapy (lisdexamfetamine), which has known abuse-potential, is FDA-approved. Topiramate is also commonly prescribed off-label for binge eating but has many contraindications. In contrast, the glucagon-like peptide-1 (GLP1) analog semaglutide has profound effects on central satiety signaling leading to reduced food intake, and has been approved for the treatment of obesity based on its efficacy and safety profile.

Pyroptosis Induction with Nanosonosensitizer-Augmented Sonodynamic Therapy Combined with PD-L1 Blockade Boosts Efficacy against Liver Cancer.

Induction of pyroptosis can promote anti-PD-L1 therapeutic efficacy due to the release of pro-inflammatory cytokines, but current approaches can cause off target toxicity. Herein, a phthalocyanine-conjugated mesoporous silicate nanoparticle (PMSN) is designed for amplifying sonodynamic therapy (SDT) to augment oxidative stress and induce robust pyroptosis in tumors. The sub-10 nm diameter structure and c(RGDyC)-PEGylated modification enhance tumor targeting and renal clearance.

A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors.

Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes. Understanding the functions of neuropeptides in vivo requires the ability to monitor their dynamics with high specificity, sensitivity, and spatiotemporal resolution. However, this has been hindered by the lack of direct, sensitive, and noninvasive tools.