METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.

Background: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.

Predicting poor performance on cognitive tests among older adults using wearable device data and machine learning: a feasibility study.

Timely implementation of interventions to slow cognitive decline among older adults requires accurate monitoring to detect changes in cognitive function. Factors known to be associated with cognition that can be gathered from accelerometers, user interfaces, and other sensors within wearable devices could be used to train machine learning models and develop wearable-based cognitive monitoring systems. Using data from over 2400 older adults in the National Health and Nutrition Examination Survey (NHANES) we developed prediction models to differentiate older adults with normal cognition from those with poor cognition based on outcomes from three cognitive tests measuring different domains of cognitive function.

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.

Association Between Sleep Efficiency Variability and Cognition Among Older Adults: Cross-Sectional Accelerometer Study.

Background: Sleep efficiency is often used as a measure of sleep quality. Getting sufficiently high-quality sleep has been associated with better cognitive function among older adults; however, the relationship between day-to-day sleep quality variability and cognition has not been well-established.

Objective: We aimed to determine the relationship between day-to-day sleep efficiency variability and cognitive function among older adults, using accelerometer data and 3 cognitive tests.

Identifying Predictive Risk Factors for Future Cognitive Impairment Among Chinese Older Adults: Longitudinal Prediction Study.

Background: The societal burden of cognitive impairment in China has prompted researchers to develop clinical prediction models aimed at making risk assessments that enable preventative interventions. However, it is unclear what types of risk factors best predict future cognitive impairment, if known risk factors make equally accurate predictions across different socioeconomic groups, and if existing prediction models are equally accurate across different subpopulations.

Objective: This paper aimed to identify which domain of health information best predicts future cognitive impairment among Chinese older adults and to examine if discrepancies exist in predictive ability across different population subsets.

CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats.

Background: Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain.

Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN.

Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice.

Nitric oxide-donating and reactive oxygen species-responsive prochelators based on 8-hydroxyquinoline as anticancer agents.

Metal ion chelators based on 8-hydroxyquinoline (8-HQ) have been widely explored for the treatment of many diseases. When aimed at being developed into potent anticancer agent, a largely unmet issue is how to avoid nonspecific chelation of metal ions by 8-HQ in normal cells or tissues. In the current work, a two-step strategy was employed to both enhance the anticancer activity of 8-HQ and improve its cancer cell specificity.

Neuroprotective Effect of -Cyclohexylethyl-[A/G]-[D/E]-X-V Peptides on Ischemic Stroke by Blocking nNOS-CAPON Interaction.

The protein-protein interaction between neuronal nitric oxide syntheses (nNOS) and the carboxy-terminal PDZ ligand of nNOS (CAPON) is a potential target for the treatment of ischemic stroke. Our previous study had identified ZLc-002 as a promising lead compound for inhibiting nNOS-CAPON coupling. To find better neuroprotective agents disrupting the ischemia-induced nNOS-CAPON interaction, a series of -cyclohexylethyl-[A/G]-[D/E]-X-V peptides based on the carboxy-terminal tetrapeptide of CAPON was designed, synthesized, and evaluated in this study.

Highly UV Resistant Inch-Scale Hybrid Perovskite Quantum Dot Papers.

Halide perovskite quantum dots (PQDs) are promising materials for diverse applications including displays, light-emitting diodes, and solar cells due to their intriguing properties such as tunable bandgap, high photoluminescence quantum yield, high absorbance, and narrow emission peaks. Despite the prosperous achievements over the past several years, PQDs face severe challenges in terms of stability under different circumstances. Currently, researchers have overcome part of the stability problem, making PQDs sustainable in water, oxygen, and polar solvents for long-term use.

Novel µ opioid antagonists derived from the µ opioid agonists endomorphin and [Dmt ]DALDA (H-Dmt-D-Arg-Phe-Lys-NH ).

Hybrid analogues of the µ opioid agonists endomorphin and [Dmt ]DALDA (H-Dmt-D-Arg-Phe-Lys-NH , Dmt = 2',6'-dimethyltyrosine) containing cis-4-amino-Pro, trans-4-amino-Pro, cis-4-aminoethyl-Pro or cis-4-guanidinylethyl-Pro in the 2 position of the peptide sequence were synthesized. None of the compounds retained high µ opioid agonist activity and, unexpectedly, substitution of cis-4-amino-Pro resulted in a novel class of potent µ opioid antagonists. In particular, the compound H-Dmt-cis-4-amino-Pro-Trp-Lys-NH (CZ-1) turned out to be a highly selective µ opioid antagonist with ~1 nM µ receptor binding affinity.

Intracerebroventricular administration of CYX-6, a potent μ-opioid receptor agonist, a δ- and κ-opioid receptor antagonist and a biased ligand at μ, δ & κ-opioid receptors, evokes antinociception with minimal constipation and respiratory depression in rats in contrast to morphine.

Mu opioid receptor (MOPr) agonists are thought to produce analgesia via modulation of G-protein-coupled intracellular signalling pathways whereas the β-arrestin2 pathway is proposed to mediate opioid-related adverse effects. Here, we report the antinociception, constipation and respiratory depressant profile of CYX-6, a potent MOPr agonist that is also a delta and a kappa opioid receptor (DOPr/KOPr) antagonist and that lacks β-arrestin2 recruitment at each of the MOPr, DOPr and the KOPr. In anaesthetised male Sprague Dawley rats, an intracerebroventricular (i.

Highly Efficient and Stable White Light-Emitting Diodes Using Perovskite Quantum Dot Paper.

Perovskite quantum dots (PQDs) are a competitive candidate for next-generation display technologies as a result of their superior photoluminescence, narrow emission, high quantum yield, and color tunability. However, due to poor thermal resistance and instability under high energy radiation, most PQD-based white light-emitting diodes (LEDs) show only modest luminous efficiency of ≈50 lm W and a short lifetime of <100 h. In this study, by incorporating cellulose nanocrystals, a new type of QD film is fabricated: CHNHPbBr PQD paper that features 91% optical absorption, intense green light emission (518 nm), and excellent stability attributed to the complexation effect between the nanocellulose and PQDs.

Fast-Response, Highly Air-Stable, and Water-Resistant Organic Photodetectors Based on a Single-Crystal Pt Complex.

Organic semiconductors demonstrate several advantages over conventional inorganic materials for novel electronic and optoelectronic applications, including molecularly tunable properties, flexibility, low-cost, and facile device integration. However, before organic semiconductors can be used for the next-generation devices, such as ultrafast photodetectors (PDs), it is necessary to develop new materials that feature both high mobility and ambient stability. Toward this goal, a highly stable PD based on the organic single crystal [PtBr (5,5'-bis(CF CH OCH )-2,2'-bpy)] (or "Pt complex (1o)") is demonstrated as the active semiconductor channel-a material that features a lamellar molecular structure and high-quality, intraligand charge transfer.

Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95/Discs Large/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity.

Background and Purpose- Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95/discs large/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery.

Orthogonal Lithography for Halide Perovskite Optoelectronic Nanodevices.

3D organic-inorganic hybrid halide perovskites have attracted great interest due to their impressive optoelectronic properties. Recently, the emergence of 2D layered hybrid perovskites, with their excellent and tunable optoelectronic behavior, has encouraged researchers to develop the next generation of optoelectronics based on these 2D materials. However, device fabrication methods of scalable patterning on both types of hybrid perovskites are still lacking as these materials are readily damaged by the organic solvents in standard lithographic processes.

Layer-edge device of two-dimensional hybrid perovskites.

Two dimensional layered organic-inorganic hybrid perovskites (2D perovskites) are potential candidates for next generation photovoltaic device. Especially, the out-of-plane surface perpendicular to the superlattice plane of 2D perovskites (layer-edge surface) has presented several exotic behaviors, such as layer-edge states which are found to be crucial for improving the efficiency of 2D perovskite solar cells. However, fundamental research on transport properties of layer-edge surface is still absent.

Surface Effect on 2D Hybrid Perovskite Crystals: Perovskites Using an Ethanolamine Organic Layer as an Example.

Despite the remarkable progress of optoelectronic devices based on hybrid perovskites, there are significant drawbacks, which have largely hindered their development as an alternative of silicon. For instance, hybrid perovskites are well-known to suffer from moisture instability which leads to surface degradation. Nonetheless, the dependence of the surface effect on the moisture stability and optoelectronic properties of hybrid perovskites has not been fully investigated.

Synthesis and Biological Evaluation of Fentanyl Analogues Modified at Phenyl Groups with Alkyls.

A series of fentanyl analogues modified at the phenyl group of the phenethyl with alkyl and/or hydroxyl and alkoxy, and the phenyl group in the anilido moiety replaced with benzyl or substituted benzyl, were synthesized. The in vitro opioid receptor functional activity of these compounds was evaluated by assessment of their ability to modulate forskolin-stimulated cAMP accumulation and by their ability to induce β-arrestin2 recruitment. Compound 12 is a potent μ-opioid (MOP) receptor agonist, a potent κ-opioid (KOP) receptor antagonist with weak β-arrestin2 recruitment activity.

Photostriction of CH NH PbBr Perovskite Crystals.

Organic-inorganic hybrid perovskite materials exhibit a variety of physical properties. Pronounced coupling between phonon, organic cations, and the inorganic framework suggest that these materials exhibit strong light-matter interactions. The photoinduced strain of CH NH PbBr is investigated using high-resolution and contactless in situ Raman spectroscopy.

[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.

CAPON-nNOS coupling can serve as a target for developing new anxiolytics.

Anxiety disorders are highly prevalent psychiatric diseases. There is need for a deeper understanding of anxiety control mechanisms in the mammalian brain and for development of new anxiolytic agents. Here we report that the coupling between neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) can serve as a target for developing new anxiolytic agents.