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Carbonyl addition serves as a strategically straightforward and versatile approach for synthesizing alcohols, which are often encountered within bioactive molecules. Herein, we present a ligand‐free, nickel‐catalyzed carbonyl addition process using organoboron reagents. This method enables efficient arylation of readily available ketones or aldehydes, affording a variety of tertiary and secondary alcohols. Key highlights of this protocol include the obviation of external ligands and the tolerance to many functional groups and heterocycles, thereby enhancing its practicality and utility in synthetic organic chemistry. [ABSTRACT FROM AUTHOR]

Traditional methods relying on metal‐ligand cooperation for activating pyridine bonds in de‐ and rearomatisation are being challenged by the abundant metal‐free element species as alternatives. Here, we investigated the de/re‐aromatisation of pyridine facilitated by pyridylamino‐functionalised silylene reactions with ketones and ketene. The reactivity outcome is highly dependent on the substituents on the ketones. By carefully tuning the steric demand of the ketone, each intermediate of the reaction sequence could be isolated. At room temperature, benzophenone and acetophenone substrates led to dearomatisation of the pyridine moiety, with the case of acetophenone showing an intermediate silaoxirane preceding dearomatisation. However, when subjected to acetone or diphenylketene, only silaoxiranes were formed without dearomatisation of the pyridine moiety. Notably, only benzophenone‐derived dearomatised species demonstrated rearomatisation upon heating. Furthermore, the reduced steric bulk of the ketene facilitated further ring expansion with another equivalent of the substrate, forming sila‐1,3‐dioxolanes. Both steric hindrance and aromatic groups collectively influence the dearomatisation of pyridine in pyridylaminosilylene reactions. [ABSTRACT FROM AUTHOR]

Whilst catalytic ketone allylation using palladium(0) is well–precedented, nickel(0)‐catalysed equivalents of such reactions remain scarce. We report here the first nickel‐catalysed allylation of ketones which uses an easily handled and inexpensive bench‐stable Ni(II) pre‐catalyst. This method avoids generation of stoichiometric by‐products via the use of readily available allyl alcohols, rather than the esters or related derivatives which are often used in such transformations. Under the optimised conditions, 25 monoallylated ketones were obtained in 16% to 98% yield and with high selectivity for the linear (E)‐isomers. [ABSTRACT FROM AUTHOR]

Transition‐metal‐catalyzed asymmetric α‐allylation of ketones is a particularly useful tool for constructing stereocenters via C−C bond formation. However, this type of reaction often necessitated the use of activated ketones or pre‐prepared enol intermediates as substrates. In this study, we developed a nickel‐catalyzed α‐allylation of unactivated cycloketones with allylic alcohols to synthesize chiral cycloketones with an α‐quaternary carbon center. The reaction affords the products with 42–97% yields, 72–86% ee, and no additive is needed, and the only by‐product is water. [ABSTRACT FROM AUTHOR]

Lameness is a common problem in Bali cattle. It is caused by various factors, both infectious and non-infectious. This study aims to evaluate the physiological changes in the levels of blood glucose and urinary ketone in lame Bali cattle. This study included 18 Bali cattle with locomotive disorders. Blood glucose levels were assessed from blood samples taken from the jugular vein, while urinary ketone levels were assessed from manually taken urine samples during urination of Bali cattle. The results showed that Bali cattle with locomotive disorders had significantly low blood glucose levels as well as mild to moderate ketonuria and thrombocytosis, which were associated with the increased energy requirements of lame cattle for maintaining postural balance. The results also suggested that the incidence of lameness in Bali cattle was relatively high.

Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers. [ABSTRACT FROM AUTHOR]

A Rh‐catalyzed asymmetric hydroboration of dialkyl ketone‐derived silyl enol ethers with HBpin has been developed using a commercially available catalyst and ligand ([RhCl (cod)]2 and MeO‐BIBOP). A variety of silyl enol ethers undergo this asymmetric transformation, providing the corresponding products with high enantioselectivity (up to 97 : 3 % er). In addition, the utility of this protocol is demonstrated by the versatile transformation of chiral borylether products to a range of valuable derivatives. [ABSTRACT FROM AUTHOR]

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation–reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C–N bond. This method selectively oxidatively cleaves the C–N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen. [ABSTRACT FROM AUTHOR]

Pursuing our recent interest concerning the catalytic activity of half-sandwich RuII complexes containing Schiff base ligands (L1 and L2), in this study new Schiff bases and their half-sandwich RuII complexes were prepared. The structures of these compounds were confirmed by a variety of spectral and physical methods such as microanalysis, FT-IR, electronic spectra, proton and carbon NMR, TGA and mass spectra. The catalytic activities of the RuII complexes toward the transfer hydrogenation of ketones to their corresponding alcohols were investigated using i-PrOH as a hydrogen source and solvent. The complexes showed high catalytic activities at catalyst concentrations of 0.01 mmol and were able to carry out transfer hydrogenation (TH) to a wide range of ketones in the presence of KOH. In general, Schiff bases recognition, the coordination chemistry, and the ketone substrates were found to influence the catalytic performance of these complexes. [ABSTRACT FROM AUTHOR]

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π–stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands. [ABSTRACT FROM AUTHOR]

The current research reports the synthesis of a library of thiosemicarbazones (3-16) through a two-step chemical transformation. All the synthesized derivatives were purified and fully characterized through mass spectrometry, NMR spectroscopy (1H-, and 13C-NMR), and IR spectroscopy. All the members of the synthesized library were found to be new except compound 8. The synthesized library was screened for its inhibition potential against the urease enzyme. Almost all the compounds exhibited potent activity with the IC50 = 5.3 ± 0.8 − 15.5 ± 0.6 µM in comparison to the thiourea and acetohydroxamic acid used as standard (IC50 = 21.1 ± 0.2, 20.5 ± 0.4 µM). While significant activity was exhibited by compounds 14 and 15 with the IC50 = 23.6 ± 0.6 and 27.3 ± 1.2 µM. Furthermore, kinetic studies were carried out to determine the inhibition mode and molecular docking was employed to recognize the ligand-enzyme interactions. Thereby, the docking results are well in the direction of the in vitro results. Compounds ((E)-N-(2,5-dichlorophenyl)-2-(4-fluorobenzylidene)hydrazine-1-carbothioamide (3) and (E)-2-(2-chlorobenzylidene)-N-(2-fluorophenyl) hydrazinecarbothioamide (5) were identified as the most potent inhibitors of urease by both the in vitro and in silico studies. [ABSTRACT FROM AUTHOR]

An efficient and selective Pd‐catalyzed 1,4‐dihydrosilylation of alkynones has been firstly described to provide a convenient access to β‐aryl carbonyl compounds under mild conditions. Various β‐aryl carbonyl compounds have been synthesized with good yields and functional group tolerance. β‐aryl carbonyl products have been shown to be further application in the synthesis of secondary alcohol, silyl‐ether, trifluoromethylsilyl‐ether and vinyl acetate derivative. [ABSTRACT FROM AUTHOR]

The analysis of volatile organic compounds (VOCs) present in various biological samples holds immense potential for non-invasive disease diagnostics and metabolic profiling. One of the biological fluids that are suitable for use in clinical practice is urine. Given the limited quantity of VOCs in the urine headspace, it's imperative to enhance their extraction into the gaseous phase and prevent any degradation of VOCs during the thawing process. The study aimed to test several key parameters (incubation time, temperature, and thawing) that can influence urine volatilome and monitor selected VOCs for their stability. The analysis in this study was performed using a BreathSpec® (G.A.S., Dortmund, Germany) device consisting of a gas chromatograph (GC) coupled with an ion mobility spectrometer (IMS). Testing three different temperatures and incubation times yielded a low number of VOCs (9 out of 34) that exhibited statistically significant differences. However, examining three thawing conditions revealed no VOCs with statistically significant changes. Thus, we conclude that urine composition remains relatively stable despite exposure to various thermal stresses. [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action. Methods: We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time. Results: A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: −0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen’s D = 0.57, 95% CI: −0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids. Conclusions: Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory. [ABSTRACT FROM AUTHOR]

In this study, we developed a bidentate Ru(II)‐NC‐catalyzed transfer hydrogen reaction of ketones using ethanol (EtOH) as the hydrogen source under weak base conditions. The control experiments suggested that the reaction proceeded via a Ru‐H mechanism, yielding ethyl acetate as the only byproduct. The deuterium‐labeling experiments showed that hydrogen evolved from the CH2 and OH groups. These results provide a new weak base system for the transfer hydrogen reaction of ketones using EtOH as the hydrogen donor. [ABSTRACT FROM AUTHOR]

Epilepsy often occurs with other neurological disorders, such as autism, affective disorders, and cognitive impairment. Research indicates that many neurological disorders share a common pathophysiology of dysfunctional energy metabolism, neuroinflammation, oxidative stress, and gut dysbiosis. The past decade has witnessed a growing interest in the use of metabolic therapies for these disorders with or without the context of epilepsy. Over one hundred years ago, the high-fat, low-carbohydrate ketogenic diet (KD) was formulated as a treatment for epilepsy. For those who cannot tolerate the KD, other diets have been developed to provide similar seizure control, presumably through similar mechanisms. These include, but are not limited to, the medium-chain triglyceride diet, low glycemic index diet, and calorie restriction. In addition, dietary supplementation with ketone bodies, polyunsaturated fatty acids, or triheptanoin may also be beneficial. The proposed mechanisms through which these diets and supplements work to reduce neuronal hyperexcitability involve normalization of aberrant energy metabolism, dampening of inflammation, promotion of endogenous antioxidants, and reduction of gut dysbiosis. This raises the possibility that these dietary and metabolic therapies may not only exert anti-seizure effects, but also reduce comorbid disorders in people with epilepsy. Here, we explore this possibility and review the clinical and preclinical evidence where available. [ABSTRACT FROM AUTHOR]

Background and Aims: New‐onset atrial fibrillation (NOAF) is a common manifestation in critically ill patients. There is a paucity of evidence indicating a relationship between urinary ketones and NOAF. Methods: Critically ill patients with urinary ketone measurements from the Medical Information Mart for Intensive Care (MIMIC‐IV) database were included. The primary outcome was NOAF Propensity score matching was performed following by multivariable logistic regression. Results: A total of 24,688 patients with available data of urine ketone were included in this study. The urine ketone of 4014 patients was tested positive. The average age of the included participants was 63.8 years old, and 54.5% of them were male. Result of the fully‐adjusted binary logistic regression model showed that patients with positive urinary ketone was associated with a significantly lower risk of NOAF (Odds ratio, 0.79, 95% CI 0.7–0.9), compared with those with negative urinary ketone. In the subgroup analysis according to diabetic status, compared with nondiabetics, patients with diabetes had lower risk of NOAF (p‐values for interaction < 0.05). Results of other subgroup analyses according to gender, age, infection, myocardial infarction, and congestive heart failure were consistent with the primary analysis. Conclusions: Positive urinary ketone body may be associated with reduced risk of NOAF in critically ill patients during intensive care unit hospitalization. Further studies are needed to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

This article discusses a new synthetic approach for the exchange reaction between ketones and vinyl ethers using solid catalysts. The authors found that Amberlyst A16 and montmorillonite K10 were effective catalysts, resulting in moderate to good yields of the desired products. The catalysts could be reused multiple times without significant decrease in yield. The article also provides chemical analyses and data for various compounds, including NMR spectra, GC-MS data, and HRMS data. [Extracted from the article]

Diabetes mellitus (DM) is one of the most challenging diseases among all the other diseases in the recent era, and it is a life-threatening disorder. The best enzymes to target for treating DM are α-glucosidase and α-amylase. For this purpose, we explored numerous succinimides with ketone functionalities. First, we explored these compounds for their in vitro analysis. Compounds 1 and 4 exhibited excellent inhibition of both enzymes in in vitro studies. These compounds displayed excellent activity with IC50 values of 3.69 and 1.526 µg·mL−1 against the α-glucosidase enzyme. In the α-amylase inhibitory assay, compound 1 has shown excellent potential with an IC50 value of 1.07 µg·mL−1 and compound 4 with an IC50 value of 0.115 µg·mL−1. Based on the in vitro analysis, the potent compounds were further subjected to their in vivo analysis. Before the in vivo analysis, the toxicity profile was checked, and it was confirmed that the compounds were safe at 1,500 µg·kg−1. Then, these compounds were subjected for their in vivo anti-diabetic potential in a mouse model of diabetes. Various concentrations of compounds 1 and 4 were explored by in vivo analysis using glibenclamide as a standard drug. The blood glucose level of the tested and control groups was measured at 0 to 15 days accordingly. Similarly, we also explored compounds 1 and 4 for the oral glucose tolerance test at 0–120 min using glibenclamide as the standard drug. Hence, the succinimide having ketone moiety displayed excellent potential against diabetes.

Background: Hyperemesis gravidarum is a common cause of nausea and vomiting during the early gestational week. At the same time, it can also lead to an increase in liver enzyme values in patients due to or independently of underlying liver disease. This study aimed to evaluate fasting bile acid (FBA) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and urine ketone levels in pregnant women diagnosed with hyperemesis gravidarum (HG). Additionally, the study sought to investigate the relationship between HG and FBA levels. The diagnosis of HG remains primarily clinical, and identifying markers for disease severity is crucial. Methods: This retrospective cohort study obtained blood samples from 50 women diagnosed with HG and 25 healthy pregnant women. Serum levels of AST, ALT, total bilirubin (TBS), direct bilirubin, urine ketones, and FBA were measured. Statistical analysis was performed using the SPSS software version 28.0. Results: FBA levels were significantly higher in pregnant women diagnosed with HG compared to the healthy control group. Additionally, FBA levels increased simultaneously with ketonuria in the patient group. Our findings suggest that FBA levels can serve as a biomarker for diagnosing HG and indicating early-stage liver damage. Unlike previous studies, our research focused on the relationship between FBA levels and HG, providing valuable insights for future studies. Conclusions: FBA levels show promise as an objective biomarker for diagnosing HG and indicating early-stage liver damage. Further research with larger cohorts is necessary to validate these findings.

The replacement of palladium catalysts for Wacker‐type oxidation of olefins into ketones by first‐row transition metals is a relevant approach for searching more sustainable protocols. Besides highly sophisticated iron catalysts, all the other first‐row transition metal complexes have only led to poor activities and selectivities. Herein, we show that the cobalt‐tetraphenylporphyrin complex is a competent catalyst for the aerobic oxidation of styrenes into ketones with silanes as the hydrogen sources. Remarkably, under room temperature and air atmosphere, the reactions were exceedingly fast (up to 10 minutes) with a low catalyst loading (1 mol %) while keeping an excellent chemo‐ and Markovnikov‐selectivity (up to 99 % of ketone). Unprecedently high TOF (864 h−1) and TON (5,800) were reached for the oxidation of aromatic olefins under these benign conditions. Mechanistic studies suggest a reaction mechanism similar to the Mukaiyama‐type hydration of olefins with a change in the last fundamental step, which controls the chemoselectivity, thanks to a unique hydrogen bonding network between the ethanol solvent and the cobalt peroxo intermediate. [ABSTRACT FROM AUTHOR]

Catalytic asymmetric allylation of ketones under proton‐transfer conditions is a challenging issue due to the limited pronucleophiles and the electrophilic inertness of ketones. Herein, a copper(I)‐catalyzed asymmetric allylation of ketones with 2‐aza‐1,4‐dienes (N‐allyl‐1,1‐diphenylmethanimines) is disclosed, which affords a series of functionalized homoallyl tertiary alcohols in high to excellent enantioselectivity. Interestingly, N‐allyl‐1,1‐diphenylmethanimines work as synthetic equivalents of propanals. Upon the acidic workup, a formal asymmetric β‐addition of propanals to ketones is achieved. An investigation on KIE effect indicates that the deprotonation of N‐allyl‐1,1‐diphenylmethanimines is the rate‐determining step, which generates nucleophilic allyl copper(I) species. Finally, the synthetic utility of the present method is demonstrated by the asymmetric synthesis of (R)‐boivinianin A and (R)‐gossonorol. [ABSTRACT FROM AUTHOR]

Electron‐accepting units play vital roles in constructing donor‐acceptor (D‐A) conjugated organic optoelectronic materials; the electronic structures and functions of the acceptors need to be carefully unveiled to controllably tailor the optoelectronic properties. We have synthesized two D‐A conjugated organic fluorophores, TPA‐SO and TPA‐CO, with similar molecular skeletons based on sulfone‐ or carbonyl‐containing polycyclic aromatic acceptors. Both TPA‐SO and TPA‐CO display obvious solvent polarity‐dependent photophysical properties and large Stokes shift of over 100 nm for strong intramolecular charge transfer processes. Experimental evidence indicates that the sulfone group in TPA‐SO merely serves as a strong electron‐withdrawing unit. TPA‐SO shows yellowish‐green emission with a peak at 542 nm and an absolute photoluminescence quantum yield (PLQY) of 98 % in solution, whereas the carbonyl group in TPA‐CO can act as both an electron‐withdrawing unit and spin transition convertor, so TPA‐CO displays red emission with a low absolute PLQY of 0.32 % in solution. Impressively, upon going from solution to aggregate state, TPA‐SO nanoparticles keep a high PLQY of 9.5 % and moderate biocompatibility, thus they are good nano‐agents for cellular fluorescence imaging. The results reveal that the inherent acceptor characteristic acts as a crucial effect in the photophysical properties and applications of the organic fluorophores. [ABSTRACT FROM AUTHOR]

This study reports an efficient and green one‐step method for synthesizing thiophene‐substituted ketones from 2‐thiophenemethanol and ketones via dehydrogenative coupling using manganese complexes as catalysts. The manganese complex demonstrated a broad applicability under mild conditions and extended the range of usable substrates. Utilizing this strategy, we carried out an efficient and diverse reaction of ketones with 2‐thiophenemethanol, and successfully synthesized a series of thiophene‐substituted saturated ketones and α, β‐unsaturated ketones in good isolated yields. [ABSTRACT FROM AUTHOR]

Fatty acids are metabolized by β‐oxidation within the "mitochondrial ketogenic pathway" (MKP) to generate β‐hydroxybutyrate (BHB), a ketone body. BHB can be generated by most cells but largely by hepatocytes following exercise, fasting, or ketogenic diet consumption. BHB has been shown to modulate systemic and brain inflammation; however, its direct effects on microglia have been little studied. We investigated the impact of BHB on Aβ oligomer (AβO)‐stimulated human iPS‐derived microglia (hiMG), a model relevant to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AβO with proinflammatory activation, which was mitigated by BHB at physiological concentrations of 0.1–2 mM. AβO stimulated glycolytic transcripts, suppressed genes in the β‐oxidation pathway, and induced over‐expression of AD‐relevant p46Shc, an endogenous inhibitor of thiolase, actions that are expected to suppress MKP. AβO also triggered mitochondrial Ca2+ increase, mitochondrial reactive oxygen species production, and activation of the mitochondrial permeability transition pore. BHB potently ameliorated all the above mitochondrial changes and rectified the MKP, resulting in reduced inflammasome activation and recovery of the phagocytotic function impaired by AβO. These results indicate that microglia MKP can be induced to modulate microglia immunometabolism, and that BHB can remedy "keto‐deficiency" resulting from MKP suppression and shift microglia away from proinflammatory mitochondrial metabolism. These effects of BHB may contribute to the beneficial effects of ketogenic diet intervention in aged mice and in human subjects with mild AD. [ABSTRACT FROM AUTHOR]

Background The ketone body 3‐hydroxybutyrate (3‐OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3‐OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D‐3‐OHB and L‐3‐OHB, remain undetermined. Methods and Results Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3‐hour infusions of either D/L‐3‐OHB (racemic mixture), 100% L‐3‐OHB, 100% D‐3‐OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure‐volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high‐resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D‐[11C]3‐OHB and L‐[11C]3‐OHB positron emission tomography. All three 3‐OHB infusions increased 3‐OHB levels (P

BackgroundAlzheimer’s disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action.MethodsWe conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time.ResultsA total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: −0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen’s D = 0.57, 95% CI: −0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids.ConclusionsAttrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

Background and aimsIncreasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet (KD) intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the KD would reduce a neurobiological craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues.MethodsWe performed a secondary analysis of functional magnetic resonance data of 33 adults with an AUD who were randomized to a KD (n = 19) or a standard American diet (SA; n = 14) and underwent 3 weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently established ‘Neurobiological Craving Signature’ (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues.ResultsFor alcohol relative to food cues, there was a main effect of group, such that the KD group showed lower NCS expression across all 3 weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score.ConclusionA ketogenic diet reduces self-reported alcohol wanting, and induced lower NCS to alcohol cues during inpatient treatment for AUD. However, in the KD group alcohol wanting continued to decrease across the 3 weeks of abstinence while the NCS scores remained stable, suggesting that this cue-induced NCS may not fully capture ongoing, non-cue-induced alcohol desire.

Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation–reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C–N bond. This method selectively oxidatively cleaves the C–N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

Point-of-care (POC) glucose and β-hydroxybutyrate (β-HB) meters can potentially provide rapid insight into an elasmobranch’s metabolic state in clinical and field research settings. This study evaluated the diagnostic agreement of three commercial POC meters against reference laboratory methods for glucose and β-HB concentrations in stingrays. Blood was collected during anesthetized exams from 28 stingrays representing four species: cownose rays (Rhinoptera bonasus), Atlantic stingrays (Hypanus sabina), southern stingrays (Hypanus americanus), and yellow stingrays (Urobatis jamaicensis). Glucose and β-HB concentrations were measured with each POC meter using whole blood and plasma; in parallel, plasma glucose and β-HB concentrations were measured via reference laboratory methods. Agreement between POC meters and reference laboratory methods was assessed using Bland–Altman methods, Passing-Bablok regression, observed total error, percent relative error, and linear mixed effect models. Plasma glucose and β-HB concentrations determined by reference laboratory methods ranged from

Background: Social affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated. Results: In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After 1 month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with exogenous ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity. Conclusions: Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality. [ABSTRACT FROM AUTHOR]

We herein reported the design and synthesis of a ferrocene‐based tetradentate ligand that is featured with modular synthesis and rigid skeleton. Its iron(II) complex facilitates asymmetric direct hydrogenation of ketones without the participation of extra strong‐field ligand such as CO and isocyanide. Hydride donor lithium aluminum hydride (LAH) converted non‐reactive Fe(II) species to reactive Fe(II) hydride species. With this catalyst, various chiral alcohols including the intermediate for montelukast could be prepared with satisfactory yields and enantioinduction. [ABSTRACT FROM AUTHOR]

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is generally developed with excessive accumulation of lipids in the liver. Ketogenesis is an efficient pathway for the disposal of fatty acids in the liver and its metabolic benefits have been reported. In this review, we examined previous studies on the association between ketogenesis and MAFLD and reviewed the candidate mechanisms that can explain this association. [ABSTRACT FROM AUTHOR]

An asymmetric Mn/TEMPO-Salen complex was utilized as a reducing agent and template for the synthesis of Mn/TEMPO-doped Fe3O4 NPs in situ. The subsequent thermal decomposition of Mn/TEMPO-doped Fe3O4 NPs, as a precursor, provides the highly porous (641 m2 g–1) Mn2O3-doped Fe3O4 NPs. The highly porous NPs was characterized by FTIR, BET, TGA, VSM, ICP, TEM, XRD, UV–Vis, and XPS analyses. High stability and catalytic activity was found for the NPs in the synthesis of α-aminonitriles via the Strecker synthesis from primary and secondary alcohols under mild conditions. TAIm[CN] ionic liquid (IL) was used as an efficient solvent and nitrile-required reagent to synthesis of α-aminonitriles. TAIm[CN] IL could be recycled for several times by a simple recovery and subsequent treatment. Also, the catalytic activity of the NPs was evaluated toward the selective alcohol oxidation to carbonyl compounds and the direct transformation of imines from alcohols and aryl amines. Mn2O3-doped Fe3O4 NPs could be recovered and reused for several consecutive cycles without any considerable reactivity loss. Highly porous MnO-doped Fe3O4 NPs were synthesized via thermal decomposition of Mn/TEMPO-doped Fe3O4 NPs as a precursor, and used as an efficient recyclable catalyst for the Strecker synthesis from alcohols in TAIm[CN] ionic liquid [ABSTRACT FROM AUTHOR]

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The formation of C-C bonds is at the very heart of synthetic chemistry for building the carbon skeleton of molecules. This chapter gives an overview of the catalytic systems developed in recent years based on 3d metals for the α-alkylation of ketones with primary and secondary alcohols by hydrogen auto-transfer. [ABSTRACT FROM AUTHOR]

Julia‐Kocienski olefination, a coupling reaction between a carbonyl component and a sulfone partner, has emerged as a powerful synthetic tool in the preparation of several organic compounds. A number of interesting examples involving particularly the preparation of trisubstituted alkenes along with important observations regarding the stereoselectivity of those reactions have been recently reported. This reviewing work covers the literature for the period 2016–2022 and describes in a comprehensive way the progress and developments of Julia‐Kocienski olefination application in the synthesis of trisubstituted alkenes which serve as precursors of natural products and their analogs as well of pharmaceutically interesting/biologically important compounds. Moreover, key methodology results dealing with the investigation of the optimum conditions and stereoselectivities and new modifications and approaches are discussed. [ABSTRACT FROM AUTHOR]

Diboron compounds are important reagents in a series of transition metal catalyzed or metal‐free borylation reactions. We describe herein a unique reactivity of 4‐Bpin‐o‐carborane with ketones under basic conditions, leading to sequential cage carbon alkylation, B−B bond activation and unexpected O‐migration. The reaction was compatible with a good substrate scope including dialkyl or alkyl aryl ketones. The reaction mechanism is also proposed, involving cage CH deprotonation, nucleophilic attack of ketone, and O‐migration along with B−B bond cleavage. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel method for chemodivergent deoxygenative- and alkoxy-carbonylation of alcohols. • With boronic acids as the reaction partner, esters and ketones can be produced selectively. • This protocol features excellent regioselectivity and broad substrate scope. • Highly base-sensitive boronic acid substrates can also be applied under base-free conditions. A method for the chemodivergent deoxygenative- and alkoxy-carbonylation of alcohols with boronic acids via palladium catalysis has been developed. Manipulation of the divergent selectivities depend on simply changing the choice of activators. While a carbodiimide activator promoted the formation of ketones through deoxygenative carbonylation, selectivity for esters via alkoxy carbonylation was observed with an azo activator. Notably, in addition to the broad substrate scope, this base-free strategy enables the use of highly base-sensitive boronic acid substrates. This study contributes to the art of chemoselectivity control in carbonylation chemistry. [ABSTRACT FROM AUTHOR]

A convenient and catalyst-free method for the α-bromination of acetophenones using NaBr and CHCl3 in biphasic electrolysis with H2SO4 as a supporting electrolyte at room temperature has been introduced. This approach results in an excellent yield of α-bromo acetophenones with high selectivity in a beaker-type cell equipped with C/SS electrodes. To achieve good yield with high current efficiency, various optimization studies are carried out and reported. [ABSTRACT FROM AUTHOR]

Catalyzed by BiCl3, aromatic o-diamines reacted with ketones efficiently to produce 1,5-benzodiazepines in good to excellent yields by condensation–cyclization reaction. Using aldehydes as substrates, mono- or disubstituted benzimidazoles were obtained as the final products. All reactions were carried out under mild reaction conditions and showed good functional group compatibility. [ABSTRACT FROM AUTHOR]

The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area. [ABSTRACT FROM AUTHOR]

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π–stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, 11C-acetoacetate (11C-AcAc), in the heart and kidney compared to 11C-acetate (11C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of 11C-Ac was higher compared to 11C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of 11C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with 11C-Ac. This suggests an equilibrium of 11C-AcAc with the other ketone, 11C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of 11C-AcAc is different compared to 11C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs.

Recently, the tactic of converting ketones into proaromatic dihydroquinazolinones and their subsequent aromatization-driven C-C bond cleavage has emerged as a promising technique for the functionalization of ketone C-C bonds. Organophotoredox-Catalyzed Oxidative C(sp2)-H Alkylation of N-Heteroarenes with Dihydroquinazolinones by C-C Cleavage [65] Activation of the N-heteroarene C-H bond and the ketone C-C bond was amalgamated under net oxidative conditions to accomplish the targeted C-C bond formation through a Minisci reaction. Keywords: photoredox catalysis; heteroarenes; ketone; C-C bond cleavage; alkylation EN photoredox catalysis heteroarenes ketone C-C bond cleavage alkylation 1241 1246 6 06/19/23 20230704 NES 230704 N-Heteroarenes form the privileged core structures of many naturally occurring alkaloids, [1] pharmaceutical drugs, [2] agrochemicals, [7] and functional materials. [Extracted from the article]