Dehydroxy-Perfluoro-tert-butylation of alcohols with PhSOC(CF) and insights into the structure of the [C(CF)] anion.

Branched PFOA and PFOS have shorter half-lives, lower toxicity, and weaker serum protein binding than linear ones, offering better environmental and health safety. Yet methods to access such branched motifs remain under developed. We now introduce a one-step dehydroxy-perfluoro-tert-butylation of alcohols, in which perfluoro-tert-butyl phenyl sulfone serves both to activate the C-O bond and to deliver the perfluoro-tert-butyl group.

Modular synthesis of CF-containing compounds with PhSOCFH reagent through difluoromethylene radical anion synthon strategy.

Difluoromethylene moiety has gained widespread applications in pharmaceuticals, agrochemicals, and materials owing to its augmented lipophilicity and being bioisosteric to ethereal oxygen. Possessing two orthogonal reactivity modes for bridging an electrophile and a radical acceptor to give gem-difluorides (R-CF-R), the efficient difluoromethylene radical anion synthon (diFRAS) has been long sought after. In this work, we successfully utilize the readily available difluoromethyl phenyl sulfone (PhSOCFH) to couple with electrophiles and radical acceptors, thereby enabling PhSOCFH to serve as a novel diFRAS in organic synthesis.

Stereoselective Nucleophilic Di- and Monofluoro(sulfoximidoyl)Methylation of C═C Bonds: Remote Neighboring Group Participation Enables Facile Access to Chiral γ-Fluorinated Amines.

There remains an ongoing challenge to develop facile methods for the preparation of chiral γ,γ-difluorinated amines, which are commonly considered a privileged motif in bioactive compounds. In this context, we report a straightforward protocol for the stereoselective nucleophilic difluoro(sulfoximidoyl)methylation of C═C bonds (considered to be more challenging than the reported C═O bonds), which exhibits high stereoselectivity and broad substrate scope. The key features of this chemistry include 1) stereoselective addition of the difluoro(sulfoximidoyl)methyl anion to C═C bonds, although it was considered to be highly unfavorable from the view of hard-soft acid-base (HSAB) theory; 2) intriguing neighboring group participation of the oxygen from the nitro group that was found to play a crucial role in controlling the stereoselectivity and efficiency of the transformation and was supported by mechanistic experiments and DFT calculations.

Metanephrines-corrected adrenal vein sampling in primary aldosteronism concurrent with autonomous cortisol secretion.

Purpose: Whether metanephrines (MNs)-corrected indices in adrenal venous sampling (AVS) would be useful in subtyping primary aldosteronism (PA) concurrent with autonomous cortisol secretion (ACS) remains unclear.

Methods: This retrospective study included PA patients concurrent with (PA/ACS) or without (isolated PA) ACS who underwent AVS. Firstly, optimal cut-offs for the metanephrine-based selectivity index (SI) and normetanephrine-based SI (SI) were determined using cortisol-corrected SI (SI≥2) as the reference in the isolated PA group.

Ferroptosis triggers anti-tumor immunity via promoting chaperone-mediated autophagic degradation of SHP2.

Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, plays a significant role in various physiological and pathological processes, including cancer. However, the connection between ferroptosis and anti-tumor immunity remains incompletely understood. Our investigation demonstrates that ferroptosis inducers like RSL3 can enhance the efficacy of anti-PD-1 therapy by activating the STAT1 signaling pathway.

Perirenal Adipose Tissue and Hypertension: Observational and Genetic Analyses.

Background: Perirenal adipose tissue (PRAT) consists of white and brown adipocytes with good vascularization and dense innervation, which could influence the blood pressure. We aim to investigate the association of PRAT thickness with risks of overall and specific forms of hypertension.

Methods: We measured PRAT thickness in the UK Biobank and CONPASS (Chongqing Primary Aldosteronism Study).

Indole selectively suppresses aldosterone overproduction via binding to the catalytic site of CYP11B2.

Hyperaldosteronism, characterized by aldosterone overproduction, increases the risk of renal damage and cardiovascular events. Aldosterone synthase (CYP11B2), the rate-limiting enzyme in aldosterone biosynthesis, has emerged as a promising therapeutic target, but developing selective CYP11B2 inhibitors remains challenging due to its high structural similarity to 11β-hydroxylase (CYP11B1). Indole, a natural heterocyclic compound derived from plants and bacteria, has therapeutic and regulatory effects in inflammation and endocrinology.

Comparison of different criteria of captopril challenge test for the diagnosis of primary aldosteronism.

Objectives: The Captopril Challenge Test (CCT) is favored in the diagnosis of primary aldosteronism (PA) for its simplicity and high patient compliance, yet optimal diagnostic criteria for CCT remain controversial. This study compared the accuracy of different CCT criteria for the diagnosis of PA.

Methods: This study included retrospective and prospective cohorts.

Synthesis of Perfluoro--butyl Triazoles via Decarboxylative CuAAC of (Perfluoro--butyl)propiolic Acid with Azides.

A copper-catalyzed decarboxylative cycloaddition of (perfluoro--butyl)propiolic acid (PFtPA) with azides under mild conditions was developed, enabling the facile synthesis of perfluoro--butyl (PFtB) triazoles. The strong electron-withdrawing nature of the PFtB group facilitates efficient decarboxylative cycloaddition at 30 °C using catalytic copper acetate, avoiding the requirement of traditional harsh conditions. This method provides high yields of products and is compatible with a wide range of azides (including bioactive molecules).

Browning of Aldosterone-Producing Adenoma Adjacent Adipose Tissue Involved in Aldosterone Synthesis Regulation.

Aldosterone-producing adenoma (APA) is a benign adrenal tumor that results in persistent autonomous aldosterone secretion. Current studies indicate a close association between adjacent adipose tissue and tumor progression. Here, we preliminarily explore the association between APA and adjacent adipocytes.

Plasmon-assisted channel-tunable bistable states in a monolayer MoS nanoresonator coupled to a metallic nanoshell.

We study how to obtain the channel-tunable bistable states in a coupled system consisting of a monolayer MoS nanomechanical resonator (NR) and a metallic nanoshell (MNS) beyond the dipole approximation. The MNS is constructed by a metallic core and a dielectric shell. The calculated results show that the linear absorption spectrum exhibits some new features, such as three-phonon resonance, Rayleigh resonance, and ac-Stark resonance.

Surgical decision in patients with primary aldosteronism based on adrenal veins aldosterone not corrected by cortisol.

Background: Cortisol-corrected aldosterone concentration is used to interpret adrenal venous sampling (AVS) results to identify the subtype of primary aldosteronism. Whether AVS could be interpreted using aldosterone without cortisol correction is unclear.

Purpose: To evaluate the accuracy of plasma aldosterone concentration (PAC) and aldosterone ratio (PAC of the higher side divided by PAC of the lower side) of the adrenal veins for the diagnosis of unilateral PA (UPA).

Postdiagnosis physical activity and dietary inflammatory and insulinemic potential with overall survival in men with nonmetastatic prostate cancer.

Inflammation and insulin resistance are associated with increased mortality in the general population. However, it remains unclear how physical activity and proinflammatory/hyperinsulinemic diets influence overall survival in prostate cancer patients. We analyzed 4779 men with nonmetastatic prostate cancer from the Health Professionals Follow-up Study.

A novel nonsense mutation of the glucocorticoid receptor gene causing glucocorticoid resistance with infertility.

Purpose: Chrousos syndrome is a rare disease mainly caused by inactivated mutations in the NR3C1 gene, which encodes the human glucocorticoid receptor (GR). We reported a male patient of Chrousos syndrome, who had a novel nonsense mutation (c.1839T > A, p.

-Activation of 2-PySOCFH for Electrophilic Difluoromethylthiolation of Electron-Rich Heteroarenes.

Difluoromethyl 2-pyridyl sulfone (2-PySOCFH) is a readily accessible, cost-effective, and versatile reagent with broad applications in fluoroalkylation and fluoroolefination. Here, we unveil a novel application of 2-PySOCFH in electrophilic difluoromethylthiolation. Key to this advance is the strategic -activation of 2-PySOCFH to generate stable -methylpyridinium salt and pyridine -oxide derivatives.

Adaptive Dual-Task Deep Learning for Automated Thyroid Cancer Triaging at Screening US.

Purpose To develop an adaptive dual-task deep learning model (ThyNet-S) for detection and classification of thyroid lesions at US screening. Materials and Methods This retrospective study used a multicenter dataset comprising 35 008 thyroid US images of 23 294 individual examinations (mean age, 40.4 years ± 13.

Residential environment and risk of chronic diseases: A prospective study.

The impact of green-blue spaces on human health remains inconclusive, and the current understanding of disease spectrum associated with these spaces is still incomplete. We aimed to comprehensively investigate the relationship between residential environment and chronic diseases, while also examining the potential mediating role of air pollutants in these relationships. Using data from the UK Biobank, we created a residential environment score (RES) based on four types of green-blue spaces: natural environment, green space, domestic garden, and water area, with scores assigned according to the percentage of each space within a 300 m buffer.

Protocol for constructing in vivo and in vitro models integrating clinical and proteomic subtypes of chordoma.

Here, we present a protocol for constructing both in vivo and in vitro models of chordoma, integrating clinical and proteomic subtyping to enable a comprehensive analysis. We detail the steps for tissue sample preparation and tandem mass tag proteomic analysis and apply non-negative matrix factorization for molecular classification. Furthermore, we classify chordoma cell lines and establish cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models in mice for investigating drug response.

From -Fluoroalkylation to Fluoroalkylation-Thiolation: Difunctionalization of Alkenes with Fluoroalkyl Phenyl Sulfones and Thiophenols Enabled by Photoredox Copper Catalysis.

Molecules containing fluoroalkyl and arylthio groups play a pivotal role in pharmaceutical and agrochemical development. The simultaneous introduction of these functional groups through the 1,2-difunctionalization of alkenes is an efficient strategy. Fluoroalkyl phenyl sulfones serve as accessible fluoroalkyl radical precursors; however, their tendency to interact with thiophenol via the electron donor-acceptor interaction mechanism can impede the desired transformation.

Oxygen clusters anchoring Co ions in hollow tungstic acid spheres to promote the generation of singlet oxygen for New Coccine degradation.

In this study, distinctive hollow spheres assembled by interlaced tungstic acid nanosheets (HWO) are synthesized through a facile self-template method. Cobalt ions were strongly coordinated with the oxygen cluster in tungstic acid, successfully preparing the Co/HWO composite for use as a peroxymonosulfate (PMS) activator. Owing to the synergistic effect between oxygen clusters and Co active component as well as the interlaced nanosheets-shells with hollow interior in Co/HWO, the composite exhibits appealing degradation performance, achieving 100% degradation of New Coccine (NC) in 40 min.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Validating Machine Learning Models Against the Saline Test Gold Standard for Primary Aldosteronism Diagnosis.

Background: In this study, we developed and validated machine learning models to predict primary aldosteronism (PA) in hypertensive East-Asian patients, comparing their performance against the traditional saline infusion test. The motivation for this development arises from the need to provide a more efficient and standardized diagnostic approach, because the saline infusion test, although considered a gold standard, is often cumbersome, is time-consuming, and lacks uniform protocols. By offering an alternative diagnostic method, this study seeks to enhance patient care through quicker and potentially more reliable PA detection.

Balanced diets are associated with a lower risk of type 2 diabetes than plant-based diets.

Background & Aims: Plant-based diets benefit human health, while the deficient in some nutrients limits its application. We aimed to examine whether balanced diets could be better in reducing diabetes risk than plant-based diets.

Methods: In cross-sectional analysis of Environment-Inflammation-Metabolic-Diseases Study (EIMDS), we used a questionnaire to investigate the habit of balanced and plant-based diets.

KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis.

Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional landscape of CS and the mechanisms by which key genes contribute to chemotherapy resistance could be a crucial step in overcoming this challenge. To address this, we developed a single-cell transcriptional map of CS, comparing it with OS and normal cancellous bone.