Aged Brain Metabolomics Study by Metabolic Profiling Analysis of Amino Acids, Organic Acids, and Fatty Acids in Cortex, Cerebellum, Hypothalamus, and Hippocampus of Rats.

Background: Aging is a progressive process characterized by weakness in brain function. Although metabolomics studies on the brain related with aging have been conducted, it is not yet fully understood. A systematic metabolomics study was performed to search for biomarkers and monitor altered metabolism in various brain tissues of the cortex, cerebellum, hypothalamus, and hippocampus of young (8 months old) and old rats (22 months old).

Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice.

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements.

Investigating perceptions and attitude toward telenursing among undergraduate nursing students for the future of nursing education: a cross-sectional study.

Background: Telenursing is poised to emerge as a novel healthcare delivery system in the digital age. Hence, understanding nursing students' perspectives and readiness is pivotal for its effective implementation. This study investigated nursing students' perceptions regarding, and attitudes toward, telenursing and the factors that influenced their attitudes based on the technology acceptance model.

Gas Evolution Kinetics in Overlithiated Positive Electrodes and its Impact on Electrode Design.

Increasing lithium contents within the lattice of positive electrode materials is projected in pursuit of high-energy-density batteries. However, it intensifies the release of lattice oxygen and subsequent gas evolution during operations. This poses significant challenges for managing internal pressure of batteries, particularly in terms of the management of gas evolution in composite electrodes-an area that remains largely unexplored.

PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor.

Double Emulsion-Mediated Delivery of Polyphenol Mixture Alleviates Atopic Dermatitis.

Although the polyphenols have been studied to alleviate inflammation, there are still challenges to delivering the polyphenols with stabilized formulation due to their low water solubility and susceptibility to oxidation. Herein, the transdermal delivery system of polyphenol mixture (PM), including quercetin (Q), phloretin (P), and ellagic acid (E), is developed using double emulsion for applying to atopic dermatitis (AD). Through the in vitro anti-degranulation assay, the optimal molar ratio of each polyphenol (Q:P:E = 5:1:1) is obtained, and the PM shows at most a 43.

5-methylthiopentyl Isothiocyanate, a Sulforaphane Analogue, Inhibits Pro-inflammatory Cytokines by Regulating LPS/ATP-mediated NLRP3 Inflammasome Activation.

Background: Pro-inflammatory cytokines secreted from activated macrophages and astrocytes are crucial mediators of inflammation for host defense. Among them, the secretion of IL-1β, a major pro-inflammatory cytokine, is especially mediated by the activation of NLRP3 inflammasome. Pro-IL-1β, which is produced in response to the invaded pathogens, such as LPS, is cleaved and matured in the NLRP3 inflammasome by the recognition of ATP.

The Molecular Mechanisms of Neuroinflammation in Alzheimer's Disease, the Consequence of Neural Cell Death.

Alzheimer's disease (AD) is accompanied by neural cell loss and memory deficit. Neural cell death, occurring via apoptosis and autophagy, is widely observed in the AD brain in addition to neuroinflammation mediated by necroptosis and the NLRP3 inflammasome. Neurotoxicity induced by amyloid-beta (Aβ) and tau aggregates leads to excessive neural cell death and neuroinflammation in the AD brain.

The Derivatives of Cromolyn Ameliorate the Abnormal Misfolding of Amyloid Proteins and Neuroinflammation in the Neural Cells.

Background: The representative symptom of Alzheimer's Disease (AD) has mainly been mentioned to be misfolding of amyloid proteins, such as amyloid-beta (Aβ) and tau protein. In addition, the neurological pathology related to neuroinflammatory signaling has recently been raised as an important feature in AD. Currently, numerous drug candidates continue to be investigated to reduce symptoms of AD, including amyloid proteins misfolding and neuroinflammation.

Solid-State Reaction Heterogeneity During Calcination of Lithium-Ion Battery Cathode.

During solid-state calcination, with increasing temperature, materials undergo complex phase transitions with heterogeneous solid-state reactions and mass transport. Precise control of the calcination chemistry is therefore crucial for synthesizing state-of-the-art Ni-rich layered oxides (LiNi Co Mn O , NRNCM) as cathode materials for lithium-ion batteries. Although the battery performance depends on the chemical heterogeneity during NRNCM calcination, it has not yet been elucidated.

A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.

Background: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing.

Methods: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway).

Reclassification of clinically-detected sequence variants: Framework for genetic clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group UK).

Purpose: Variant classifications may change over time, driven by emergence of fresh or contradictory evidence or evolution in weighing or combination of evidence items. For variant classifications above the actionability threshold, which is classification of likely pathogenic or pathogenic, clinical actions may be irreversible, such as risk-reducing surgery or prenatal interventions. Variant reclassification up or down across the actionability threshold can therefore have significant clinical consequences.

Association between Olfactory Receptors and Skin Physiology.

Olfactory receptors are chemosensory receptors that detect odorants and function in the initial perception of a smell. Intriguingly, olfactory receptors are also expressed in cells other than olfaction sensory cells, an expression pattern termed ectopic expression. Ectopically expressed olfactory receptors have a distinct role depending on the type of tissues or cells in which they are expressed.

Templated synthesis of microparticles with carbonaceous skeletal structures using polymer cubosomes as templates.

Polymer cubosomes (PCs) are bicontinuous mesoporous colloidal particles that feature high surface areas and an extremely ordered crystalline pore network. PCs have attracted tremendous attention because of their potential applications in many fields. Herein, we obtained new microparticles with carbonaceous reticulated networks templated synthesis using PCs as templates.

A chemical tool for blue light-inducible proximity photo-crosslinking in live cells.

We developed a proximity photo-crosslinking method () with a 4-azido--ethyl-1,8-naphthalimide (AzNP) moiety that can be converted to reactive aryl nitrene species using ambient blue light-emitting diode light. Using an AzNP-conjugated HaloTag ligand (VL1), blue light-induced photo-crosslinked products of various HaloTag-conjugated proteins of interest were detected in subcellular spaces in live cells. Chemical or heat stress-induced dynamic changes in the proteome were also detected, and photo-crosslinking in the mouse brain tissue was enabled.

Metabolomic analysis of amino acids and organic acids in aging mouse eyes using gas chromatography-tandem mass spectrometry.

This is a metabolomics study for monitoring altered amino acid (AA) and organic acid (OA) metabolism of in eyes from aging an mouse model at 8 and 18 weeks and 18 months. Simultaneous metabolic profiling analysis of OAs and AAs was performed as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-tandem mass spectrometry. A total of 42 metabolites-24 AAs and 18 OAs-were determined and their composition values were normalized to the corresponding mean values of 8-week-old mice as the control group.

Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.

Purpose: The weight of the evidence to attach to observation of a novel rare missense variant in SDHB or SDHD in individuals with the rare neuroendocrine tumors, pheochromocytomas and paragangliomas (PCC/PGL), is uncertain.

Methods: We compared the frequency of SDHB and SDHD very rare missense variants (VRMVs) in 6328 and 5847 cases of PCC/PGL, respectively, with that of population controls to generate a pan-gene VRMV likelihood ratio (LR). Via windowing analysis, we measured regional enrichments of VRMVs to calculate the domain-specific VRMV-LR (DS-VRMV-LR).

Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.

Purpose: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice.

Methods: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications.

Suppressing High-Current-Induced Phase Separation in Ni-Rich Layered Oxides by Electrochemically Manipulating Dynamic Lithium Distribution.

Understanding the cycling rate-dependent kinetics is crucial for managing the performance of batteries in high-power applications. Although high cycling rates may induce reaction heterogeneity and affect battery lifetime and capacity utilization, such phase transformation dynamics are poorly understood and uncontrollable. In this study, synchrotron-based operando X-ray diffraction is performed to monitor the high-current-induced phase transformation kinetics of LiNi Co Mn O .

Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts.

Background & Aims: Colorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYNOTE 177 clinical trial) or nivolumab to dissect the cellular and molecular determinants of response to anti- programmed cell death 1 (PD1) immunotherapy.

Methods: We selected multiple regions per tumor showing variable T-cell infiltration for a total of 738 regions from 29 patients, divided into discovery and validation cohorts.

Natural Products Targeting Amyloid Beta in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe brain damage and dementia. There are currently few therapeutics to treat this disease, and they can only temporarily alleviate some of the symptoms. The pathogenesis of AD is mainly preceded by accumulation of abnormal amyloid beta (Aβ) aggregates, which are toxic to neurons.

Non-precious-metal catalysts for alkaline water electrolysis: operando characterizations, theoretical calculations, and recent advances.

Recent years have witnessed an upsurge in the development of non-precious catalysts (NPCs) for alkaline water electrolysis (AWE), especially with the strides made in experimental and computational techniques. In this contribution, the most recent advances in NPCs for AWE were systematically reviewed, emphasizing the application of in situ/operando experimental methods and density functional theory (DFT) calculations in their understanding and development. First, we briefly introduced the fundamentals of the anode and cathode reaction for AWE, i.