Site-Selective C(sp)-H and Switchable C(sp)-H/C(sp)-H Functionalization Enabled by Electron-Deficient Cp*Ir(III) Catalyst and Photosensitizer.

A site-selective functionalization of a C(sp)-H bond was achieved in the presence of an intrinsically more reactive C(sp)-H bond by controlling the orientation of a directing group via a photo-induced E/Z isomerization of an oxime ether. By combining E/Z isomerization and an electron deficient Cp*Ir(III) catalyst, the scope of oxime ethers in C(sp)-H functionalization was successfully expanded. Based on this strategy, the order of C-H activation was switchable and successive C(sp)-H/C(sp)-H and C(sp)-H/C(sp)-H double functionalizations were accomplished to construct densely functionalized structures.

Cobalt/Photoredox Dual-Catalyzed Cross-Radical Coupling of Alkenes via Hydrogen Atom Transfer and Homolytic Substitution.

Cobalt-catalyzed metal hydride hydrogen atom transfer (MHAT) in combination with photoredox catalysis has emerged as a powerful synthetic method, owing to its redox nature and applicability to various radical precursors. Herein, we describe a cross-radical coupling reaction under cobalt/photoredox dual catalysis. MHAT and homolytic substitution (S2) processes enabled Markovnikov-selective hydrobenzylation of di/trisubstituted alkenes, affording products with a quaternary carbon center in a redox-neutral manner.

Adult-onset Acute Flaccid Myelitis Accompanied by Rhombencephalitis Which First Presented with Prominent Psychiatric Symptoms and Dysautonomia Mimicking Anti-N-methyl-D-aspartate Receptor Encephalitis.

A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac arrest occurred, which required pacemaker placement. She subsequently showed profound flaccid limb paralysis, with magnetic resonance imaging demonstrating focal necrotic lesions localized in the anterior horn of the longitudinal segments of the spinal cord and in the pontine tegmentum.

Inhibition of the mitochondrial respiratory chain reduces catecholamine‑stimulated lipolysis via increasing lactate production in 3T3‑L1 adipocytes.

Adipose tissue serves a significant role in the regulation of energy metabolism in the body. The re‑esterification of the fatty acids generated during lipolysis is critical for efficient lipolysis. However, the effect of the intracellular energy state on lipolytic activity and fatty acid re‑esterification during lipolysis is not yet fully understood.

Photocatalytic 1,2-Phosphorus-Migrative [3 + 2] Cycloaddition of Tri(-butyl)phosphine with Terminal Alkynes.

Tri(-butyl)phosphine and terminal alkynes undergo 1,2-phosphorus-migrative [3 + 2] cycloaddition in the presence of a proton source under photocatalytic conditions. The reaction exhibits broad functional group tolerance and affords substituted cyclic phosphonium salts, which are amenable to further derivatization by Wittig olefination. Theoretical studies suggest that the phosphorus 1,2-migration of a β-phosphonioalkyl radical proceeds through a phosphine radical cation-alkene complex as a pseudointermediate, and the two fragments in the intermediate are bound to each other through multiple noncovalent interactions.

Gold-Zinc Cooperative Catalysis for Seven-exo-dig Hydrocarboxylation of Internal Alkynes.

Seven-exo-dig hydrocarboxylation of nonactivated internal alkynes with conformationally flexible linker chains was achieved with cooperative gold-zinc catalysts composed of an imidazo[1,5-a]pyridinylidene ligand including a bipyridine coordination site at the C5 position. A proximity effect of the gold and zinc sites was essential for their high catalytic activity, in which the internal alkyne activated by the cationic gold species was attacked by the carboxylic acid deprotonated by the basic zinc site. Using a gold(I)-complex with a bulky aromatic N-substituent, 2,6-dibenzhydryl-4-methylphenyl group, for the NHC ligand facilitated seven-membered ring formation while minimizing intermolecular hydrocarboxylation as an undesired side reaction.

Intermittent fasting reduces mouse body fat while maintaining muscle mass by regulating protein synthesis and autophagy.

Objectives: The aim of this study is to investigate the effect of intermittent fasting (IF) on the regulation of skeletal muscle protein metabolism in response to nutrient supplementation during fasting.

Methods: Twelve-week-old male C57BL/6J mice were assigned to two groups: ad libitum and IF, with the latter having access to food for only 3 h/d. After 6 wk of experimental periods, an oral glucose tolerance test was performed.

Dimetal-Binding Scaffold 2-(Pyridin-2-yl)imidazo [1,5-b]pyridazine-7-ylidene: Synthesis of Trinuclear Heterobimetallic Complexes Involving Gold-Metal Interactions.

As a dimetal-binding rigid scaffold, 2-(pyridin-2-yl)imidazo[1,5-b]pyridazine-7-ylidene was introduced. The scaffold was first converted into a meridional Au,N,N-tridentate ligand through binding of a Au(I)Cl moiety at the carbene center. The Au(I) center and the N,N-chelating moiety were expected to function as metallophilic and 4e-σ-donative interaction sites, respectively, in the binding of the second metal center.

Visible-Light-Induced Aminochlorination of Alkenes.

Photoinduced -internal vicinal aminochlorination of styrene-type terminal alkenes was developed. The reaction proceeded without any catalyst, and the use of -chloro(fluorenone imine) as both a photoactivatable aminating agent and a chlorinating agent was essential. The imine moiety, introduced at the internal position of the alkenes, could be hydrolyzed under mild conditions to provide versatile β-chlorinated primary amines, the synthetic utility of which was demonstrated by several transformations.

Interaction Between Sarcopenic Obesity and Nonlocomotive Physical Activity on the Risk of Depressive Symptoms in Community-Dwelling Older Adult Japanese Women.

This study aimed to investigate the interaction between sarcopenic obesity and locomotive and nonlocomotive physical activity (PA) on the risk of depressive symptoms in community-dwelling older Japanese women. Participants were 143 community-dwelling older women aged 64-94 years. PA was measured using a three-axis accelerometer.

Nickel-Catalyzed Defluorophosphonylation of Aryl Fluorides.

A Ni-catalyzed cross-coupling reaction between aryl fluorides and dialkyl phosphonates [HP(O)(OR)] (R = secondary alkyl groups) in the presence of potassium -butoxide as a base is reported. The reaction converted various aryl fluorides into the corresponding aryl phosphonates even when electron-donating substituents were present on the aromatic ring. The combined experimental and computational studies suggested Ni-K cooperative action of a Ni(0) complex chelated with a strongly electron-donating ion-bridged dimeric phosphite ligand system [P(OR)OK] that facilitates turnover-limiting C-F bond oxidative addition of aryl fluorides.

Progressive supranuclear palsy with predominant frontal presentation exhibiting progressive nonfluent aphasia due to crossed aphasia.

Progressive supranuclear palsy (PSP) with predominant frontal presentation (PSP-F) is a clinical phenotype of PSP that is characterized by frontal cognitive impairment and behavioral changes. Here, we report on a patient with pathologically diagnosed PSP-F in whom we were able to observe temporal changes of the clinical manifestations. A 77-year-old right-handed man developed progressive nonfluent aphasia (PNFA) at the age of 69 years, festinating gait, and clumsiness of his left arm at age 75, disinhibition at age 76, and unprovoked falls at age 77.

Low-carbohydrate, high-fat diet, and running exercise influence bone parameters in old mice.

We examined the effects and interactions of a low-carbohydrate, high-fat (LCHF) diet and voluntary running exercise on bone in older mice. Male 19-mo-old mice were divided into four groups by diet (control vs. LCHF) and exercise (sedentary vs.

Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION.

BDK knockout skeletal muscle satellite cells exhibit enhanced protein translation initiation signal in response to BCAA in vitro.

We examined the effects of branched-chain amino acids (BCAAs) and electrical pulse stimulation (EPS) on the mTORC1 pathway in muscle satellite cells (MSCs) isolated from branched-chain α-keto acid dehydrogenase kinase (BDK) knockout (KO) mice in vitro. MSCs were isolated from BDK KO and wild-type (WT) mice, proliferated, and differentiated into myotubes. BCAA stimulation increased the phosphorylation of p70 S6 kinase (p70S6K), a marker of protein translation initiation, in MSCs from WT and BDK KO mice, but the rate of the increase was higher in MSCs isolated from BDK KO mice.

c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle.

High-intensity muscle contractions (HiMCs) are known to increase c-Myc expression that is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, although c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, this connection has not been tested directly. We investigated the effect of adeno-associated virus (AAV)-mediated c-Myc overexpression, with or without fasting or percutaneous electrical stimulation-induced HiMC, on ribosome biogenesis and protein synthesis in adult mouse skeletal muscles.

Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue.

Background: During lipolysis, triglyceride (TG) are hydrolyzed into a glycerol and fatty acids in adipocyte. A significant portion of the fatty acids are re-esterificated into TG, and this is a critical step in promoting lipolysis. Although glycerol-3-phosphate (G3P) is required for triglyceride synthesis in mammalian cell, the substrate for G3P synthesis during active lipolysis is not known.

Basal and resistance exercise-induced increase in protein synthesis is impaired in skeletal muscle of iron-deficient rats.

Objectives: We aimed to investigate the effect of iron deficiency on basal- and contraction-induced increases in muscle protein synthesis.

Methods: Four-wk-old male Sprague-Dawley rats were divided into three groups. The rats in two of the three groups had free access to a control diet (AD) or iron-deficient diet (ID) for 4 wk.

Chronobiology of transient global amnesia.

Introduction: The etiology of transient global amnesia (TGA) is still a matter of debate. Based, among others, on the observation of a close temporal relation between certain events and subsequent TGA episodes, recent proposals discuss the relevance of stress-associated processes impacting on hippocampal functioning. Circadian, infra- and ultradian rhythmicity has been found to play a relevant role in the multifactorial pathomechanisms of various disorders but has not been thoroughly studied in TGA.

Phosphinylation of Non-activated Aryl Fluorides through Nucleophilic Aromatic Substitution at the Boundary of Concerted and Stepwise Mechanisms.

Non-activated aryl fluorides reacted with potassium diorganophosphinites through a nucleophilic aromatic substitution (S Ar) reaction. Remarkably, both electron-neutral and electron-rich aryl fluorides participated in the reaction with substantially stabilized anionic P nucleophiles to form the corresponding tertiary phosphine oxides. Quantum chemical calculations suggested a nucleophile-dependent mechanism that involves both concerted and stepwise S Ar reaction pathways.

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats.

Recent studies of the ketogenic diet, an extremely high-fat diet with extremely low carbohydrates, suggest that it changes the energy metabolism properties of skeletal muscle. However, ketogenic diet effects on muscle metabolic characteristics are diverse and sometimes countervailing. Furthermore, ketogenic diet effects on skeletal muscle performance are unknown.