Catalytic Amino Group Transfer Reactions Mediated by Photoinduced Nitrene Formation from Rhodium-Hydroxamates.

Herein, we report a photocatalytic platform to access transient nitrenoids by designing photo-responsive neutral rhodium-hydroxamate complexes. Combined experimental and computational mechanistic studies, including electron paramagnetic resonance (EPR) and mass spectrometric analysis, suggest that electrophilic Fischer-type Rh-acylnitrenoid intermediates could be generated via photoactivation of corresponding Rh-hydroxamates via N-O bond homolysis and redox event. Moreover, catalytic acylnitrenoid transfer was explored toward the amidation of various hydrocarbons, amines, and alcohols to furnish new N-C, N-N, and N-O bonds.

Zn(ii)-driven impact of monomeric transthyretin on amyloid-β amyloidogenesis.

Extracellular accumulation of amyloid-β (Aβ) peptides in the brain plays a significant role in the development of Alzheimer's disease (AD). While the co-localization and interaction of proteins and metal ions with Aβ in extracellular milieu are established, their precise pathological associations remain unclear. Here we report the impact of Zn(ii) on the anti-amyloidogenic properties of monomeric transthyretin (M-TTR), which coexists spatially with Aβ and Zn(ii) in extracellular fluids.

Distinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).

The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.

Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.

Alzheimer's disease (AD) is the most prevalent neurodegenerative dementia, marked by progressive cognitive decline and memory impairment. Despite advances in therapeutic research, single-target-directed treatments often fall short in addressing the complex, multifactorial nature of AD. This arises from various pathological features, including amyloid-β (Aβ) aggregate deposition, metal ion dysregulation, oxidative stress, impaired neurotransmission, neuroinflammation, mitochondrial dysfunction, and neuronal cell death.

Multi-target macrocycles: pyrogallol derivatives to control multiple pathological factors associated with Alzheimer's disease.

Designing multi-target chemical tools is a vital approach to understanding the pathology of Alzheimer's disease (AD), which involves a complex network of pathological factors, such as free organic radicals, amyloid-β (Aβ), and metal-bound Aβ (metal-Aβ). The pyrogallol moiety, known for its ability to lower redox potentials and interact with both Aβ and metal ions, presents a promising framework for this molecular design. Here we show how simple structural variations of pyrogallol can be used to enhance its ability to scavenge free organic radicals and regulate the aggregation of both metal-free Aβ and metal-Aβ.

Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation.

Neurodegenerative disorders (NDDs) are a class of debilitating diseases that progressively impair the protein structure and result in neurological dysfunction in the nervous system. Among these disorders, Alzheimer's disease (AD), prion diseases such as Creutzfeldt-Jakob disease (CJD), and Parkinson's disease (PD) are caused by protein misfolding and aggregation at the cellular level. In recent years, transition metal complexes have gained significant attention for their potential applications in diagnosing, imaging, and curing these NDDs.

Ultrasmall Mn-doped iron oxide nanoparticles with dual hepatobiliary and renal clearances for MR liver imaging.

Although magnetic nanoparticles demonstrate significant potential as magnetic resonance imaging (MRI) contrast agents, their negative contrasts, liver accumulation, and limited excretion hinder their application. Herein, we developed ultrasmall Mn-doped iron oxide nanoparticles (UMIOs) with distinct advantages as MRI contrast agents. Exceptionally small particle sizes ( 2 nm) and magnetization values (5 emu g) of UMIOs provided optimal contrast effects with an ideally low / value of ∼1.

Decoding the Parkinson's Symphony: PARIS, Maestro of Transcriptional Regulation and Metal Coordination for Dopamine Release.

Parkin interacting substrate (PARIS) is a pivotal transcriptional regulator in the brain that orchestrates the activity of various enzymes through its intricate interactions with biomolecules, including nucleic acids. Notably, the binding of PARIS to insulin response sequences (IRSs) triggers a cascade of events that results in the functional loss in the substantia nigra, which impairs dopamine release and, subsequently, exacerbates the relentless neurodegeneration. Here, we report the details of the interactions of PARIS with IRSs via classical zinc finger (ZF) domains in PARIS, namely, PARIS(ZF2-4).

APP-C31: An Intracellular Promoter of Both Metal-Free and Metal-Bound Amyloid-β Aggregation and Toxicity in Alzheimer's Disease.

Intracellular C-terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP-C31 that is suspected to be involved in the pathology of AD. But details about the role of APP-C31 in the development of the disease are not known. Here, this work reports that APP-C31 directly interacts with the N-terminal and self-recognition regions of amyloid-β (Aβ ) to form transient adducts, which facilitates the aggregation of both metal-free and metal-bound Aβ peptides and aggravates their toxicity.

TGF-β and SHH Regulate Pluripotent Stem Cell Differentiation into Brain Microvascular Endothelial Cells in Generating an In Vitro Blood-Brain Barrier Model.

Blood-brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging.

Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease.

The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-β, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets.

Transition metal ions and neurotransmitters: coordination chemistry and implications for neurodegeneration.

Neurodegeneration is characterized by a disturbance in neurotransmitter-mediated signaling pathways. Recent studies have highlighted the significant role of transition metal ions, including Cu(i/ii), Zn(ii), and Fe(ii/iii), in neurotransmission, thereby making the coordination chemistry of neurotransmitters a growing field of interest in understanding signal dysfunction. This review outlines the physiological functions of transition metal ions and neurotransmitters, with the metal-binding properties of small molecule-based neurotransmitters and neuropeptides.

Mechanistic snapshots of rhodium-catalyzed acylnitrene transfer reactions.

Rhodium (Rh) acylnitrene complexes are widely implicated in catalytic C-H amidation reactions but have eluded isolation and structural characterization. To overcome this challenge, we designed a chromophoric octahedral Rh complex with a bidentate dioxazolone ligand, in which photoinduced metal-to-ligand charge transfer initiates catalytic C-H amidation. X-ray photocrystallographic analysis of the Rh-dioxazolone complex allowed structural elucidation of the targeted Rh-acylnitrenoid and provided firm evidence that the singlet nitrenoid species is primarily responsible for acylamino transfer reactions.

Influence of hepatic dysfunction in patients who underwent tricuspid valve surgery.

Background: Hepatic dysfunction (HD) is frequently associated with chronic tricuspid regurgitation (TR), and is a risk factor for TR surgery. Late referral of patients with TR is associated with the progression of TR and HD, as well as an increase in surgical morbidity and mortality. Many patients with severe TR suffer from HD; however, their clinical impact is not well documented.

Direct Extracorporeal Membrane Oxygenation Bridged Heart Transplantation: The Importance of Multi-Organ Failure.

Background And Objectives: Recently, approximately 40% of all heart transplantation (HTx) in South Korea are performed using the direct extracorporeal membrane oxygenation (ECMO) bridging method. We conducted a study to examine the clinical outcome of direct ECMO-bridged HTx and to investigate the impact of multi-organ failure (MOF).

Methods: From June 2014 to September 2022, a total of 96 adult patients who underwent isolated HTx at a single tertiary hospital were included in the study.

The Clinical Outcomes of Marginal Donor Hearts: A Single Center Experience.

Background And Objectives: Although the shortage of donor is a common problem worldwide, a significant portion of unutilized hearts are classified as marginal donor (MD) hearts. However, research on the correlation between the MD and the prognosis of heart transplantation (HTx) is lacking. This study was conducted to investigate the clinical impact of MD in HTx.

Commentary: Does Patch Repair of the Interatrial Septum Minimize the Incidence of Postoperative Atrial Tachyarrhythmia?

See Article page 186.

Current understanding of metal-dependent amyloid-β aggregation and toxicity.

The discovery of effective therapeutics targeting amyloid-β (Aβ) aggregates for Alzheimer's disease (AD) has been very challenging, which suggests its complicated etiology associated with multiple pathogenic elements. In AD-affected brains, highly concentrated metals, such as copper and zinc, are found in senile plaques mainly composed of Aβ aggregates. These metal ions are coordinated to Aβ and affect its aggregation and toxicity profiles.

Controlling π-π Interactions of Highly Soluble Naphthalene Diimide Derivatives for Neutral pH Aqueous Redox Flow Batteries.

Organic redox-active molecules are a promising platform for designing sustainable, cheap, and safe charge carriers for redox flow batteries. However, radical formation during the electron-transfer process causes severe side reactions and reduces cyclability. This problem is mitigated by using naphthalene diimide (NDI) molecules and regulating their π-π interactions.

Methods for analyzing the coordination and aggregation of metal-amyloid-β.

The misfolding and aggregation of amyloid-β (Aβ) peptides are histopathological features found in the brains of Alzheimer's disease (AD). To discover effective therapeutics for AD, numerous efforts have been made to control the aggregation of Aβ species and their interactions with other pathological factors, including metal ions. Metal ions, such as Cu(II) and Zn(II), can bind to Aβ peptides forming metal-bound Aβ (metal-Aβ) complexes and, subsequently, alter their aggregation pathways.

Surgical Outcomes of Cardiac Myxoma Resection Through Right Mini-Thoracotomy.

Background: With recent advances in cardiac surgery through minimal access, mini-thoracotomy has emerged as an excellent alternative for cardiac myxoma resection. This study analyzed the surgical results of this approach, focusing on postoperative cerebral embolism and tumor recurrence.

Methods: We retrospectively reviewed 64 patients (mean age, 56.