Bis(aminoalkyl)cyclopropenylidene (BAC)-Catalyzed Intramolecular Annulation of 2-(2-Formylaryl)-aryl-Substituted -Quinone Methides to 9-Phenanthrol Derivatives.

This article describes a bis(aminoalkyl)cyclopropenylidene (BAC)-catalyzed intramolecular annulation of strategically designed 2-(2-formylaryl)-phenyl-substituted -quinone methides (QMs) to access 9-phenanthrol derivatives and related carbocycles. In addition, the synthetic utility of this methodology has been demonstrated in the synthesis of the seven-membered carbocyclic core of resveratrol-based natural products (±)-shoreaphenol and (±)-malibatol A.

Domino Approach to Heterocycles-Based Unsymmetrical Triarylmethanes through Heteroannulation of 2-(2-Enynyl)-pyridines with Enaminones.

Herein, we report a copper-catalyzed protocol to access unsymmetrical triarylmethanes containing both indolizine and the chromone scaffolds in the same molecule via a 5--dig cyclization of 2-(2-enynyl)-pyridines followed by reaction with 2-hydroxyaryl enaminones. A variety of 2-hydroxyaryl enaminones and 2-(2-enynyl)-pyridines were subjected to reaction under the optimal reaction conditions, and the respective triarylmethanes were obtained in good to excellent yields.

A HMPA-HO mediated oxygenative carbocyclization of 2-alkynylphenyl-substituted -quinone methides to indenones.

Herein, we report a transition-metal and base-free protocol to access a wide range of functionalized indenone derivatives through a HMPA-HO-mediated oxygenative annulation of 2-alkynylphenyl-substituted -quinone methides. This method worked effectively for most of the -QMs investigated and the corresponding indenone derivatives were obtained in moderate to good yields. This methodology was further extended to the formal synthesis of one of the resveratrol based natural products, (±)-isopaucifloral F.

Bringing Artificial Intelligence to the operating room: edge computing for real-time surgical phase recognition.

Background: Automation of surgical phase recognition is a key effort toward the development of Computer Vision (CV) algorithms, for workflow optimization and video-based assessment. CV is a form of Artificial Intelligence (AI) that allows interpretation of images through a deep learning (DL)-based algorithm. The improvements in Graphic Processing Unit (GPU) computing devices allow researchers to apply these algorithms for recognition of content in videos in real-time.

Surgical Phase Recognition in Inguinal Hernia Repair-AI-Based Confirmatory Baseline and Exploration of Competitive Models.

Video-recorded robotic-assisted surgeries allow the use of automated computer vision and artificial intelligence/deep learning methods for quality assessment and workflow analysis in surgical phase recognition. We considered a dataset of 209 videos of robotic-assisted laparoscopic inguinal hernia repair (RALIHR) collected from 8 surgeons, defined rigorous ground-truth annotation rules, then pre-processed and annotated the videos. We deployed seven deep learning models to establish the baseline accuracy for surgical phase recognition and explored four advanced architectures.

Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle.

Muscle contraction is driven by the molecular machinery of the sarcomere. As phosphorylation is a critical regulator of muscle function, the identification of regulatory kinases is important for understanding sarcomere biology. Pathogenic variants in alpha kinase 3 (ALPK3) cause cardiomyopathy and musculoskeletal disease, but little is known about this atypical kinase.

Pd(II)-catalyzed annulation of terminal alkynes with 2-pyridinyl-substituted -quinone methides: direct access to indolizines.

A Pd-catalyzed direct method has been developed to access 1,3-disubstituted indolizines. This reaction proceeds through a regiospecific annulation of terminal alkynes with 2-pyridinyl-substituted -quinone methides and, in most of the cases, the desired 1,3-disubstituted indolizines were obtained in moderate to good isolated yields. The control experiments suggested that the reaction does proceed through a substrate-controlled regiospecific formal [3 + 2]-annulation pathway.

TfOH-Catalyzed Intramolecular Annulation of 2-(Aryl)-Phenyl-Substituted -Quinone Methides under Continuous Flow: Total Syntheses of Selaginpulvilin I and Isoselagintamarlin A.

In this article, we describe a convenient method to access 9-aryl fluorene derivatives through a TfOH-catalyzed intramolecular 1,6-conjugate arylation of 2-(aryl)-phenyl-substituted -quinone methides (QMs) under continuous flow using the microreaction technique. This method was found to be very effective for most of the -QMs, and the corresponding 9-aryl fluorene derivatives were obtained in moderate to excellent yields. Moreover, this protocol was further elaborated to the first total syntheses of selaginpulvilin I and isoselagintamarlin A.

Recent advances in the organocatalytic applications of cyclopropene- and cyclopropenium-based small molecules.

The development of novel small molecule-based catalysts for organic transformations has increased noticeably in the last two decades. A very recent addition to this particular research area is cyclopropene- and cyclopropenium-based catalysts. At one point in time, particularly in the mid-20 century, much attention was focused on the structural aspects and physical properties of cyclopropene-based compounds.

Cysteamine Decreases Low-Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low-Density Lipoprotein Receptor-Deficient Mice.

Background We have shown previously that low-density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor-deficient mice fed a high-fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor-deficient mice were fed a high-fat diet to induce atherosclerotic lesions.

Bis(amino)cyclopropenium Ion as a Hydrogen-Bond Donor Catalyst for 1,6-Conjugate Addition Reactions.

The catalytic application of the bis(amino)cyclopropenium ion has been investigated in conjugate addition reactions. The hydrogen atom, which is attached to the cyclopropene ring of bis(amino)cyclopropenium salts, is moderately acidic and can potentially serve as a hydrogen-bond donor catalyst in some organic transformations. This hypothesis has been successfully realized in the 1,6-conjugate addition reactions of -quinone methides with various nucleophiles such as indole, 2-naphthol, thiols, phenols, and so forth.

Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice.

Background And Aims: We have shown previously that low density lipoprotein (LDL) aggregated by vortexing is internalised by macrophages and oxidised by iron in lysosomes to form the advanced lipid/protein oxidation product ceroid. We have now used sphingomyelinase-aggregated LDL, a more pathophysiological form of aggregated LDL, to study lysosomal oxidation of LDL and its inhibition by antioxidants, including cysteamine (2-aminoethanethiol), which concentrates in lysosomes by several orders of magnitude. We have also investigated the effect of cysteamine on atherosclerosis in mice.

A Cascade Synthesis of Hetero-arylated Triarylmethanes Through a Double 5-endo-dig Cyclization Sequence.

A sequential two-step method for the synthesis of hetero-arylated triarylmethanes through a Ag-catalyzed sequential double cyclization-nucleophilic addition cascade is described. This methodology basically involves an initial 5-endo-dig cyclization of o-alkynyl anilines to provide 2-substituted indole derivatives, which then react with 2-(2-enynyl)-pyridines to afford indolizine-containing unsymmetrical triarylmethanes through another 5-endo-dig cyclization.

Lysosomal oxidation of LDL alters lysosomal pH, induces senescence, and increases secretion of pro-inflammatory cytokines in human macrophages.

We have shown that aggregated LDL is internalized by macrophages and oxidized in lysosomes by redox-active iron. We have now investigated to determine whether the lysosomal oxidation of LDL impairs lysosomal function and whether a lysosomotropic antioxidant can prevent these alterations. LDL aggregated by SMase (SMase-LDL) caused increased lysosomal lipid peroxidation in human monocyte-derived macrophages or THP-1 macrophage-like cells, as shown by a fluorescent probe, Foam-LPO.

The synthetic glycolipid-based TLR4 antagonist FP7 negatively regulates in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling.

TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.

Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: A possible explanation as to why the clinical trials of antioxidants might have failed.

Oxidised low density lipoprotein (LDL) was considered to be important in the pathogenesis of atherosclerosis, but the large clinical trials of antioxidants, including the first one using probucol (the PQRST Trial), failed to show benefit and have cast doubt on the importance of oxidised LDL. We have shown previously that LDL oxidation can be catalysed by iron in the lysosomes of macrophages. The aim of this study was therefore to investigate the effectiveness of antioxidants in preventing LDL oxidation at lysosomal pH and also establish the possible mechanism of oxidation.

Pharmacognostic standardization, antioxidant and free radical scavenging activity of the seeds of Triticum aestivum L - A dietary staple.

Aims: To establish the Quality standards of Triticum aestivum L, seeds as per WHO guidelines. To study the antioxidant and hepatoprotective profile of T. aestivum L.

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

Objective: To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L.

Methods: Preliminary phytochemical investigation was done as per standard procedures.

Role of natural herbs in the treatment of hypertension.

Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness.