Freestanding Penta-Twinned Pd-Ag Nanosheets.

2D metal nanosheets have attracted significant attention as efficient catalysts for various important chemical reactions. However, the development of metal nanosheets with controlled compositions and morphologies has been slow due to the challenges associated with synthesizing thermodynamically unfavorable 2D structures. Herein, we report a synthesis route of freestanding Pd-Ag penta-twinned nanosheets (Pd-Ag ptNSs) with distinct 5-fold twin boundaries.

Highly potent and selective PPARδ agonist reverses memory deficits in mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by neurotoxicity, excessive inflammation, and cognitive impairment. The peroxisome proliferator-activated receptor (PPAR) δ is a potential target for AD. However, its regulatory mechanisms and therapeutic potential in AD remain unclear.

Discovery and Optimization of a Series of Vinyl Sulfoximine-Based Analogues as Potent Nrf2 Activators for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which leads to demyelination, axonal loss, and neurodegeneration. Increased oxidative stress and neurodegeneration have been implicated in all stages of MS, making neuroprotective therapeutics a promising strategy for its treatment. We previously have reported vinyl sulfones with antioxidative and anti-inflammatory properties that activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that induces the expression of cytoprotective genes against oxidative stress.

Synthesis and biological evaluation of O-benzyl-hispidol derivatives and analogs as dual monoamine oxidase-B inhibitors and anti-neuroinflammatory agents.

Design, synthesis, and biological evaluation of two series of O-benzyl-hispidol derivatives and the analogous corresponding O-benzyl derivatives aiming to develop selective monoamine oxidase-B inhibitors endowed with anti-neuroinflammatory activity is reported herein. The first O-benzyl-hispidol derivatives series afforded several more potentially active and MAO-B inhibitors than the O-benzyl derivatives series. The most potential compound 2e of O-benzyl derivatives elicited sub-micromolar MAO-B IC of 0.

Investigation of bio-based rigid polyurethane foams synthesized with lignin and castor oil.

In this study, polyurethane (PU) foams were manufactured using kraft lignin and castor oil as bio-based polyols by replacing 5-20 wt% and 10-100 wt% of conventional polyol, respectively. To investigate the effects of unmodified bio-based polyols on PU foam production, reactivity and morphology within PU composites was analyzed as well as mechanical and thermal properties of the resulting foams. Bio-based PU foam production was carried out after characterizing the reagents used in the foaming process (including hydroxyl group content, molecular weight distribution, and viscosity).

Phloroglucinol Derivatives Exert Anti-Inflammatory Effects and Attenuate Cognitive Impairment in LPS-Induced Mouse Model.

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration.

Detection and isolation of wormhole nodes in wireless ad hoc networks based on post-wormhole actions.

The wormhole attack is one of the most treacherous attacks projected at the routing layer that can bypass cryptographic measures and derail the entire communication network. It is too difficult to prevent a priori; all the possible countermeasures are either too expensive or ineffective. Indeed, literature solutions either require expensive hardware (typically UWB or secure GPS transceivers) or pose specific constraints to the adversarial behavior (doing or not doing a suspicious action).

Diagnostic Value of a Wearable Continuous Electrocardiogram Monitoring Device (AT-Patch) for New-Onset Atrial Fibrillation in High-Risk Patients: Prospective Cohort Study.

Background: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation.

Objective: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHADS-VASc) score had increased detection rates.

Uric acid regulates α-synuclein transmission in Parkinsonian models.

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson's disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model.

Exploration of Tetrahydroisoquinoline- and Benzo[]azepine-Based Sphingosine 1-Phosphate Receptor 1 Agonists for the Treatment of Multiple Sclerosis.

Because of the wide use of Fingolimod for the treatment of multiple sclerosis (MS) and its cardiovascular side effects such as bradycardia, second-generation sphingosine 1-phosphate receptor 1 (S1P1) agonist drugs for MS have been developed and approved by FDA. The issue of bradycardia is still present with the new drugs, however, which necessitates further exploration of S1P1 agonists with improved safety profiles for next-generation MS drugs. Herein, we report a tetrahydroisoquinoline or a benzo[]azepine core-based S1P1 agonists such as and after systematic examination of hydrophilic groups and cores.

Synthesis and Biological Evaluation of -Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases.

Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells' death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels.

Optimization and evaluation of pyridinyl vinyl sulfones as Nrf2 activator for the antioxidant and anti-inflammatory effects.

Many studies have reported that chalcone-based compounds exhibit biological activities such as anticancer, antioxidant, anti-inflammatory and neuroprotective effects. Among the published chalcone derivatives, (E)-1-(3-methoxypyridin-2-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one (VEDA-1209), which is currently undergoing preclinical study, was selected as a starting compound for the development of new nuclear factor erythroid 2-related factor 2 (Nrf2) activators. Based on our previous knowledge, we attempted to redesign and synthesize VEDA-1209 derivatives by introducing the pyridine ring and sulfone moiety to ameliorate its Nrf2 efficacy and drug-like properties.

The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function.

Differences in dietary patterns related to metabolic health by gut microbial enterotypes of Korean adults.

Diet has a profound impact on the progression of metabolic syndrome (MetS) into various diseases. The gut microbiota could modulate the effect of diet on metabolic health. We examined whether dietary patterns related to MetS differed according to gut microbial enterotypes among 348 Korean adults aged 18-60 years recruited between 2018∼2021 in a cross-sectional study.

Predictors of stroke or systemic embolism in patients with non-valvular atrial fibrillation with CHA DS -VASc score of 0.

Background: Anticoagulant therapy has been important for stroke prevention in patients with atrial fibrillation (AF). However, it was not recommended due to its relatively higher risk of bleeding than its lower risk of stroke in patients with a CHA DS -VASc score of 0.

Hypothesis: This study aimed to evaluate the predictors of stroke in AF patients with very low risk of stroke.

Anti-Apoptotic and Anti-Inflammatory Effects of an Ethanolic Extract of Root against Particulate Matter 10-Induced Cell Death and Inflammation in RBL-2H3 Basophil Cells and BALB/c Mice.

Particulate matters (PMs) from polluted air cause diverse pulmonary and cardiovascular diseases, including lung inflammation. While the fruits (Goji) of trees are commonly consumed as traditional medicine and functional food ingredients, the majority of their roots are discarded as by-products. To enhance the industrial applicability of roots, we prepared an ethanol extract (named GR30) of Miller roots and evaluated its potential protective effects against particulate matter 10 (PM10)-induced inflammation and immune cell death.

Sulfated Glucuronorhamnoxylan from Capsosiphon fulvescens Ameliorates Osteoporotic Bone Resorption via Inhibition of Osteoclastic Cell Differentiation and Function In Vitro and In Vivo.

Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-κB ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model.

Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P) Receptor Agonists.

Sphingosine-1-phosphate-1 (S1P) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P receptor internalization assay to evaluate functionally antagonistic S1P receptor agonist activity.

Aloe emodin 3-O-glucoside inhibits cell growth and migration and induces apoptosis of non-small-cell lung cancer cells via suppressing MEK/ERK and Akt signalling pathways.

Aims: Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer with a high mortality rate. Glycosylation of phenolic compounds may increase water-solubility and pharmacological activities and reduce the toxicity of aglycones. This study aimed to evaluate and compare the anticancer effect of aloe emodin 3-O-glucoside (AE3G) and its aglycone, aloe emodin (AE), against NSCLC.

Positional scanning of natural product hispidol's ring-B: discovery of highly selective human monoamine oxidase-B inhibitor analogues downregulating neuroinflammation for management of neurodegenerative diseases.

Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed.

Discovery of Novel Sphingosine-1-Phosphate-1 Receptor Agonists for the Treatment of Multiple Sclerosis.

The sphingosine-1-phosphate-1 (S1P) receptor agonists have great potential for the treatment of multiple sclerosis (MS) because they can inhibit lymphocyte egress through receptor internalization. We designed and synthesized triazole and isoxazoline derivatives to discover a novel S1P agonist for MS treatment. Of the two scaffolds, the isoxazoline derivative was determined to have excellent efficacy and drug-like properties.