Copper-Catalyzed Enantioconvergent Radical C(sp3 )-N Cross-Coupling: Access to α,α-Disubstituted Amino Acids.

Transition-metal catalyzed enantioconvergent cross-coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α-disubstituted amino acids. However, the construction of chiral C-N bonds between tertiary-carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper-catalyzed enantioconvergent radical C-N cross-coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N-ligand with a long spreading side arm. An array of α,α-disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α-fully substituted amine building blocks.

A Counterion/Ligand-Tuned Chemo- and Enantioselective Copper-Catalyzed Intermolecular Radical 1,2-Carboamination of Alkenes.

The copper-catalyzed enantioselective intermolecular radical 1,2-carboamination of alkenes with readily accessible alkyl halides is an appealing strategy for producing chiral amine scaffolds. The challenge arises from the easily occurring atom transfer radical addition between alkyl halides and alkenes and the issue of enantiocontrol. We herein describe a radical alkene 1,2-carboamination with sulfoximines in a highly chemo- and enantioselective manner. The key to the success of this process is the conceptual design of a counterion/highly sterically demanded ligand coeffect to promote the ligand exchange of copper(I) with sulfoximines and forge chiral C-N bonds between alkyl radicals and the chiral copper(II) complex. The reaction covers alkenes bearing distinct electronic properties, such as aryl-, heteroaryl-, carbonyl-, and aminocarbonyl-substituted ones, and various radical precursors, including alkyl chlorides, bromides, iodides, and the CF3 source. Facile transformations deliver many chiral amine building blocks of interest in organic synthesis and related areas.

Potential Novel Serum Metabolic Markers Associated With Progression of Prediabetes to Overt Diabetes in a Chinese Population.

Background: Identifying the metabolite profile of individuals with prediabetes who turned to type 2 diabetes (T2D) may give novel insights into early T2D interception. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population. Methods: We used an untargeted metabolomics approach to investigate the associations between serum metabolites and risk of prediabetes who turned to overt T2D (n=153, mean follow up 5 years) in a Chinese population (REACTION study). Results were compared with matched controls who had prediabetes at baseline [age: 56 ± 7 years old, body mass index (BMI): 24.2 ± 2.8 kg/m2] and at a 5-year follow-up [age: 61 ± 7 years old, BMI: 24.5 ± 3.1 kg/m2]. Confounding factors were adjusted and the associations between metabolites and diabetes risk were evaluated with multivariate logistic regression analysis. A 10-fold cross-validation random forest classification (RFC) model was used to select the optimal metabolites panels for predicting the development of diabetes, and to internally validate the discriminatory capability of the selected metabolites beyond conventional clinical risk factors. Findings: Metabolic alterations, including those associated with amino acid and lipid metabolism, were associated with an increased risk of prediabetes progressing to diabetes. The most important metabolites were inosine [odds ratio (OR) = 19.00; 95% confidence interval (CI): 4.23-85.37] and carvacrol (OR = 17.63; 95% CI: 4.98-62.34). Thirteen metabolites were found to improve T2D risk prediction beyond eight conventional T2D risk factors [area under the curve (AUC) was 0.98 for risk factors + metabolites vs 0.72 for risk factors, P < 0.05]. Interpretations: Use of the metabolites identified in this study may help determine patients with prediabetes who are at highest risk of progressing to diabetes.

Application of BOLD MRI and DTI for the evaluation of renal effect related to viscosity of iodinated contrast agent in a rat model.

PURPOSE: To evaluate the effects of viscosity of contrast agent (CA) on intrarenal oxygenation and diffusion as measured by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in a rat model. MATERIALS AND METHODS: Radiocontrast iodixanol formulated in three viscosities were designated 270, 320, and 350 (mg iodine/mL). Sixty-three male Wistar rats were divided into four groups. Saline and iodixanol (4 g iodine/kg) were administered. MR images were acquired on a 3.0T scanner at baseline and at 1 hour, 24 hours, 48 hours, and 72 hours postinjection of solutions. BOLD-MRI was performed with a multiple gradient-recalled-echo sequence. The changes in R2*, apparent diffusion coefficient (ADC), fractional anisotropy (FA), histology, and hypoxia-inducible factor-1α (HIF-1α) immunoexpression were evaluated. The R2*, ADC, and FA values were normalized to baseline to calculate ΔR2*, ΔADC, and ΔFA. RESULTS: Compared with baseline levels, distinct elevation of ΔR2* (P < 0.05) and obvious decrease in ΔADC (P < 0.01) and ΔFA (P < 0.05) were observed in all the anatomical compartments at 1 hour after administration of CA. The absolute values in ΔR2*, ΔADC, and ΔFA increased with increases in CA viscosity, and differed significantly between the CA groups in renal cortex (CO), outer stripe of outer medulla (OSOM), and inner stripe of outer medulla (ISOM) (all P < 0.05). A significant positive correlation was observed between ΔR2* and HIF-1α expression (P < 0.001, r = 0.75). Significant negative correlations were observed between ΔADC, ΔFA, and pathologies in CO, OSOM, ISOM (all P < 0.001, r = -0.68-0.87; all P < 0.001, r = -0.60-0.66). CONCLUSION: The effect of CA viscosity on intrarenal oxygenation and diffusion was viscosity-dependent, and was identified using BOLD-MRI and DTI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1320-1331.

Identification of primary thyroid lymphoma with medical imaging: A case report and review of the literature.

Primary thyroid lymphoma (PTL) is a rare thyroid malignancy. Clinical diagnosis of PTL may not be easily established based on imaging studies, as the imaging features of PTL are similar to those of lymphocytic thyroiditis and primary thyroid cancer. The present study describes the case of a patient who was confirmed to have PTL by intra-operative pathological diagnosis. On color Doppler ultrasound, the PTL was shown as a significantly enlarged thyroid with reduced gland echoes. Color Doppler flow imaging showed increased blood flow. By computed tomography, the thyroid was revealed to be enlarged with reduced tissue density, particularly in the left lobe and the isthmus. In addition, calcified spots and swollen lymph nodes were evident. The clinical history of the patient was obtained and the imaging results were retrospectively analyzed. The imaging features of PTL were investigated through reviewing the literature. PTL exhibits specific features on medical imaging that aid in distinguishing it from other thyroid diseases. PTL exhibits specific features on medical imaging that aid in distinguishing PTL from other thyroid diseases, which may aid the support for clinical diagnosis and improve the clinical accuracy.

Effects of iodinated contrast agents on renal oxygenation level determined by blood oxygenation level dependent magnetic resonance imaging in rabbit models of type 1 and type 2 diabetic nephropathy.

BACKGROUND: To evaluate the effects of contrast agents containing increasing concentrations of iodine on the renal oxygenation level determined by blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) in a rabbit model of diabetic nephropathy. METHODS: BOLD-MRI was performed using saline or iodinated (I) contrast agents (200, 240, 300, 350 and 400 mg I/mL) at 1, 24, 48, and 72 h after experimentally inducing type 2 diabetic nephropathy in rabbits. Differences in renal oxygenation levels between type 1 and type 2 diabetic nephropathy were also assessed by BOLD-MRI after injecting 400 mg I/mL of contrast agent. RESULTS: Contrast agents increased the R2* values of the renal cortex, outer medulla, and inner medulla to the maximum levels at 24 h. The R2* values then decreased to their lowest levels at 72 h. The R2* was highest following injection of 400 mg I/mL, especially in the outer medulla. The R2* values were not significantly different between types 1 and 2 diabetic nephropathy. CONCLUSIONS: Iodinated contrast agents had the greatest influence on renal outer medulla oxygenation level at 24 h in type 2 diabetic nephropathy, with the greatest effects observed at the 400 mg I/mL dose level. There were no differences in BOLD-MRI values between type 1 and type 2 diabetic nephropathy after administering the contrast agent at 400 mg I/mL.