Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome.

Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy in animal models. However, the mechanisms by which Spns1 transports lysophospholipid and proton sensing remain unclear.

Synapses do not facilitate prion-like transfer of alpha-synuclein: a quantitative study in reconstructed unidirectional neural networks.

Alpha-synuclein (aSyn) aggregation spreads between cells and underlies the progression of neuronal lesions in the brain of patients with synucleinopathies such as Parkinson's diseases. The mechanisms of cell-to-cell propagation of aggregates, which dictate how aggregation progresses at the network level, remain poorly understood. Notably, while prion and prion-like spreading is often simplistically envisioned as a "domino-like" spreading scenario where connected neurons sequentially propagate protein aggregation to each other, the reality is likely to be more nuanced.

Preparation of water-soluble chitosan oligosaccharides by oxidative hydrolysis of chitosan powder with hydrogen peroxide.

Chitosan (CS) is only soluble in weak acid medium, thereby limiting its wide utilisation in the field of biomedicine, food, and agriculture. In this report, we present a method for preparing water-soluble CS oligosaccharides (COSs) at high concentration (∼10%, w/v) via the oxidative hydrolysis of CS powder with molecular weight (Mw) ∼90,000 g/mol) in 2% HO solution at ambient temperature by a two-step process, namely, the heterogeneous hydrolysis step and homogeneous hydrolysis step. The resultant COSs were characterised by gel permeation chromatography (GPC), fourier transforms infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), proton nuclear magnetic resonance spectroscopy (H NMR) and X-ray diffraction (XRD) spectroscopy.

Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer.

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to that recurred in 30% (15/30) of patients.

Metabolic flexibility differs by body composition in adults.

Background & Aims: With the rise of global cardiometabolic diseases, it is important to investigate risk factors such as obesity. Metabolic flexibility, the ability to maintain metabolic homeostasis following an acute challenge, can reflect cardiometabolic health. We investigated the association between body composition and the metabolic flexibility following meal consumption in an adult population.

Lipid measurements in the management of cardiovascular diseases: Practical recommendations a scientific statement from the national lipid association writing group.

Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements.

Apathy in a high prevalence population of moderate to severe traumatic brain injury: An investigation in Vietnam.

Objective: The reduction of goal-directed behavior, termed apathy, is a pervasive and debilitating syndrome after traumatic brain injury (TBI). However, understanding of apathy as a multifaceted construct is limited, especially in Southeast Asian nations. This study aimed to investigate the severity, insight, and psychosocial influences of apathy in executive, emotional, and initiation dimensions in Vietnam-a country with high prevalence of TBI.

Measuring Postprandial Metabolic Flexibility to Assess Metabolic Health and Disease.

Metabolic abnormalities substantially increase the risk of noncommunicable diseases, which are among the leading causes of mortality globally. Mitigating and preventing these adverse consequences remains challenging due to a limited understanding of metabolic health. Metabolic flexibility, a key tenet of metabolic health, encompasses the responsiveness of interrelated pathways to maintain energy homeostasis throughout daily physiologic challenges, such as the response to meal challenges.

Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents.

Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i.

Subchondral Bone Length in Knee Osteoarthritis: A Deep Learning-Derived Imaging Measure and Its Association With Radiographic and Clinical Outcomes.

Objective: To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity.

Methods: A fast region-based convolutional neural network was trained to crop the knee joints in sagittal dual-echo steady-state magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees.

Human casualties are the dominant cost of human-wildlife conflict in India.

Reducing the costs from human-wildlife conflict, mostly borne by marginal rural households, is a priority for conservation. We estimate the mean species-specific cost for households suffering damages from one of 15 major species of wildlife in India. Our data are from a survey of 5,196 households living near 11 wildlife reserves in India, and self-reported annual costs include crop and livestock losses and human casualties (injuries and death).

Introducing a Supportive Care Team for Advance Directive Education in a Neurological and Neurosurgical Patient Population.

Background: Patient-centered care includes delineation of patient treatment values (ie, advance care planning [ACP]). Advance care planning often includes advance directive (AD) completion and is underutilized, particularly among neurology and neurosurgery patients. Implementation of a supportive care team (SCT) in outpatient clinic settings may offer opportunities for AD education and completion.

Postprandial glycemic response differed by early life nutritional exposure in a longitudinal cohort: a single- and multi-biomarker approach.

Purpose: Populations malnourished in early life are at increased risk for cardiometabolic diseases. We assessed if improved nutrition predicts cardiometabolic function, as assessed by postprandial biomarker responses.

Methods: Participants had been randomized at the village level to receive one of two nutritional supplements as children.

Can Ensemble Deep Learning Identify People by Their Gait Using Data Collected from Multi-Modal Sensors in Their Insole?

Gait is a characteristic that has been utilized for identifying individuals. As human gait information is now able to be captured by several types of devices, many studies have proposed biometric identification methods using gait information. As research continues, the performance of this technology in terms of identification accuracy has been improved by gathering information from multi-modal sensors.

Simultaneous Three-Dimensional Vascular and Tubular Imaging of Whole Mouse Kidneys With X-ray μCT.

Concurrent three-dimensional imaging of the renal vascular and tubular systems on the whole-kidney scale with capillary level resolution is labor-intensive and technically difficult. Approaches based on vascular corrosion casting and X-ray micro computed tomography (μCT), for example, suffer from vascular filling artifacts and necessitate imaging with an additional modality to acquire tubules. In this work, we report on a new sample preparation, image acquisition, and quantification protocol for simultaneous vascular and tubular μCT imaging of whole, uncorroded mouse kidneys.

Crosslinkable polymeric contrast agent for high-resolution X-ray imaging of the vascular system.

A contrast agent for X-ray micro computed tomography (μCT), called XlinCA, that combines reliable perfusion and permanent retention and contrast properties, was developed for ex vivo imaging. The new imaging agent XlinCA features high molecular weight, low viscosity and a high iodine content.

Protein and gene markers of metabolic dysfunction and inflammation together associate with functional connectivity in reward and motor circuits in depression.

Bidirectional relationships between inflammation and metabolic dysfunction may contribute to the pathophysiology of psychiatric illnesses like depression. Metabolic disturbances drive inflammation, which in turn exacerbate metabolic outcomes including insulin resistance. Both inflammatory (e.

Leptin partially mediates the association between early-life nutritional supplementation and long-term glycemic status among women in a Guatemalan longitudinal cohort.

Background: Early-life exposure to improved nutrition is associated with decreased risk of diabetes but increased risk of obesity. Leptin positively correlates with adiposity and has glucose-lowering effects, thus it may mediate the association of early-life nutrition and long-term glycemic status.

Objectives: We aimed to investigate the role of leptin in the differential association between early-life nutrition and the risks of obesity and diabetes.

Evaluation of a Liquid Biopsy Protocol using Ultra-Deep Massive Parallel Sequencing for Detecting and Quantifying Circulation Tumor DNA in Colorectal Cancer Patients.

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling. Here, we developed a LB protocol using ultra-deep massive parallel sequencing and validated its clinical performance for detection and quantification of actionable mutations in three major driver genes ( and ).

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD).

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored.

Association of Early-Onset Alzheimer Disease With Elevated Low-Density Lipoprotein Cholesterol Levels and Rare Genetic Coding Variants of APOB.

Importance: Early-onset Alzheimer disease (EOAD) is a rare form of Alzheimer disease (AD) with a large genetic basis that is only partially understood. In late-onset AD, elevated circulating cholesterol levels increase AD risk even after adjusting for the apolipoprotein E ε4 (APOE E4) allele, a major genetic factor for AD and elevated cholesterol levels; however, the role of circulating cholesterol levels in EOAD is unclear.

Objectives: To investigate the association between circulating cholesterol levels and EOAD and to identify genetic variants underlying this possible association.

Sympathoexcitation and impaired arterial baroreflex sensitivity are linked to vascular inflammation in individuals with elevated resting blood pressure.

Elevated Resting Blood Pressure (ERBP) in the prehypertensive range is associated with increased risk of hypertension and cardiovascular disease, the mechanisms of which remain unclear. Prior studies have suggested that ERBP may be associated with overactivation and dysregulation of the sympathetic nervous system (SNS). We hypothesized that compared to normotensives (≤120/80 mmHg), ERBP (120/80-139/89 mmHg) has higher SNS activity, impaired arterial baroreflex sensitivity (BRS), and increased vascular inflammation.