Iron-Catalyzed One-Pot Cascade Reactions of Oximes with Inactivated Saturated Ketones: Entry to Highly Substituted Pyridines.

An iron-catalyzed oxidative [3 + 3] annulation of oxime esters with inactivated saturated ketones is described. This cascade strategy allows one-step rapid synthesis of various structurally important pyridines through an oxidative dehydrogenation/annulation/oxidative aromatization sequence via direct α,β-dehydrogenation of simple saturated ketones followed by annulation with oximes. This method shows good functional group tolerance, readily accessible starting materials, a wide substrate scope, high chemoselectivity, and no need for extra stoichiometric oxidant and is also applicable to the late-stage functionalization of natural products.

A 3-year follow-up study of outcomes associated with patterns of traditional acute and preventive migraine treatment: An administrative claims-based cohort study in the United States.

Objective: To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States.

Background: There are limited data on long-term (>1 year) migraine treatments patterns and associated outcomes.

Methods: This was a retrospective, observational cohort study using US claims data from the IBM MarketScan Research Database (January 2010-December 2017).

Functional role of TrIL-1β in Takifugu rubripes defense against Cryptocaryon irritans infection.

The Japanese puffer, Takifugu rubripes, is a commercially important fish species in China that is under serious threat from white spot disease (cyptocaryoniasis), which leads to heavy economic losses. We previously found that interleukin-1β (IL-1β), an important cytokine with a potential role in resistance against pathogens, was one of the most significantly differentially up-regulated proteins in the gills and spleen of T. rubripes infected by the protozoan parasite Cryptocaryon irritans.

DNA Methylation Analysis Reveals Potential Mechanism in Takifugu rubripes Against Cryptocaryon irritans Infection.

Takifugu rubripes (T. rubripes) is a valuable commercial fish, and Cryptocaryon irritans (C. irritans) has a significant impact on its aquaculture productivity.

Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

Aim: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy.

Methods: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care.

Thyroid Hormone-mediated Histone Modification Protects Cortical Neurons From the Toxic Effects of Hypoxic Injury.

Context: Thyroid hormone has been shown to have a protective role in neuronal injury, although the mechanisms have not been established. The cellular response to stress that promotes adaptation and survival has been shown to involve epigenetic modifications.

Objective: We hypothesized that the neuroprotective role of thyroid hormone was associated with epigenetic modifications of histone proteins.

Anti-SARS-CoV-2 IgM Secondary Response Was Suppressed by Preexisting Immunity in Vaccinees: A Prospective, Longitudinal Cohort Study over 456 Days.

To obtain more insight into IgM in anti-SARS-CoV-2 immunity a prospective cohort study was carried out in 32 volunteers to longitudinally profile the kinetics of the anti-SARS-CoV-2 IgM response induced by administration of a three-dose inactivated SARS-CoV-2 vaccine regimen at 19 serial time points over 456 days. The first and second doses were considered primary immunization, while the third dose was considered secondary immunization. IgM antibodies showed a low secondary response that was different from the other three antibodies (neutralizing, total, and IgG antibodies).

Intelligent Wearable Wrist Pulse Detection System Based on Piezoelectric Sensor Array.

The human radial artery pulse carries a rich array of biomedical information. Accurate detection of pulse signal waveform and the identification of the corresponding pulse condition are helpful in understanding the health status of the human body. In the process of pulse detection, there are some problems, such as inaccurate location of radial artery key points, poor signal noise reduction effect and low accuracy of pulse recognition.

A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days.

Background: Due to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection.

Objectives: To evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens.

Synthesis of spirocyclic Δ-isoxazolines [3 + 2] cycloaddition of indanone-derived ketonitrones with alkynes.

A [3 + 2] cycloaddition of indanone-derived nitrones and alkynes under mild conditions is developed, allowing facile synthesis of spirocyclicindenyl isoxazolines with structural diversity. The sequential protocol of generated ketonitrone from unsaturated ketones and -alkylhydroxylamines is also achieved successfully, affording the desired products in considerable yield with moderate to good diastereoselectivity. Moreover, the spirocyclic product can be conveniently transformed into indenyl-based allylic alcohol and enamide.

Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days.

Background: A vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.

Objectives: To evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.

Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores.

Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R) mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies.

Remission of Type 2 Diabetes Following a Short-term Intensive Intervention With Insulin Glargine, Sitagliptin, and Metformin: Results of an Open-label Randomized Parallel-Design Trial.

Objective: The aim of the study was to evaluate remission of type 2 diabetes following a short-term intervention with insulin glargine, sitagliptin/metformin, and lifestyle approaches.

Research Design And Methods: In this open multicenter trial, 102 patients with type 2 diabetes were randomized to 1) a 12-week intervention with sitagliptin/metformin, insulin glargine, and lifestyle therapy or 2) control group. Participants with HbA1c <7.

Network Pharmacology-Based and Molecular Docking-Based Analysis of Suanzaoren Decoction for the Treatment of Parkinson's Disease with Sleep Disorder.

This study is aimed at exploring the possible mechanism of action of the Suanzaoren decoction (SZRD) in the treatment of Parkinson's disease with sleep disorder (PDSD) based on network pharmacology and molecular docking. Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the bioactive components and targets of SZRD, and their targets were standardized using the UniProt platform. The disease targets of "Parkinson's disease (PD)" and "Sleep disorder (SD)" were collected by OMIM, GeneCards, and DisGeNET databases.

The Role of Thyroid Hormone in Neuronal Protection.

Thyroid hormone is essential for brain development and brain function in the adult. During development, thyroid hormone acts in a spatial and temporal-specific manner to regulate the expression of genes essential for normal neural cell differentiation, migration, and myelination. In the adult brain, thyroid hormone is important for maintaining normal brain function.

Association of Thrombus Aspiration With Time and Mortality Among Patients With ST-Segment Elevation Myocardial Infarction: A Post Hoc Analysis of the Randomized TOTAL Trial.

Importance: Patients with shorter ischemic times have a greater viable myocardium and may derive greater benefit from thrombus aspiration.

Objective: To study the association of thrombus aspiration with outcomes among patients presenting with ST-segment elevation myocardial infarction (STEMI) based on time.

Design, Setting, And Participants: The TOTAL (Thrombectomy With PCI vs PCI Alone in Patients with STEMI) trial was an international randomized clinical trial of 10 732 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) within 12 hours of symptom onset.

Persistent COUP-TFII expression underlies the myopathy and impaired muscle regeneration observed in resistance to thyroid hormone-alpha.

Thyroid hormone signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury, via activation of thyroid nuclear receptor alpha (THRA). A mouse model of resistance to thyroid hormone carrying a frame-shift mutation in the THRA gene (THRA-PV) is associated with accelerated skeletal muscle loss with aging and impaired regeneration after injury. The expression of nuclear orphan receptor chicken ovalbumin upstream promoter-factor II (COUP-TFII, or Nr2f2) persists during myogenic differentiation in THRA-PV myoblasts and skeletal muscle of aged THRA-PV mice and it is known to negatively regulate myogenesis.

Mild and efficient copper-catalyzed oxidative cyclization of oximes with 2-aminobenzyl alcohols at room temperature: synthesis of polysubstituted quinolines.

A simple and efficient ligand-free Cu-catalyzed protocol for the synthesis of polysubstituted quinolines via oxidative cyclization of oxime acetates with 2-aminobenzyl alcohols at room temperature has been developed. The presented approach provides a new synthetic pathway leading to polysubstituted quinolines with good functional group tolerance under mild conditions. Moreover, this transformation can be applied for the preparation of quinolines on a gram scale.

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial.

Importance: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging.

Objective: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy.

Design, Setting, And Participants: Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial.

Remission of Type 2 Diabetes Following a Short-term Intervention With Insulin Glargine, Metformin, and Dapagliflozin.

Objective: To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches.

Methods: We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care.

Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial.

Background and Purpose- Aortic arch atherosclerosis (AAA) is a possible source of embolism in patients with embolic stroke of undetermined source. Previous studies reported high rates of embolic events in patients with AAA, especially those with high-risk AAA. This exploratory analysis of NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) focused on patients with AAA and assessed their characteristics, stroke recurrence rates, and response to treatment.

Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS.

Background: Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients.