Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Higher Sensitivity to Thyroid Hormones May Be Linked to Maintaining the Healthy Metabolic Condition in People with Obesity: New Insight from NHANES.

INTRODUCTION: Obesity contributes to the pathogenesis of diverse metabolic diseases, yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on metabolism. Our study aimed to investigate the association between MHO and thyroid hormone sensitivity. METHODS: Thyroid hormone indices, including the thyroid-stimulating hormone (TSH) index (TSHI), the Thyrotroph Thyroxine Sensitivity Index (TTSI), the Thyroid Feedback Quantile-Based Index (TFQI), and the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), were calculated based on a non-institutionalized US sample in the National Health and Nutrition Examination Survey (NHANES, 2007-2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were employed to analyze the association between thyroid hormone indices and metabolic phenotypes. RESULTS: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included, with 1,539 having obesity and 235 identified as MHO. Participants in the MHO group exhibited lower levels of TSH, TSHI, TTSI, TFQI, and PTFQI compared with the MHNO group (all p < 0.05), while the differences among MHNO, MUNO, and MUO groups were not statistically significant (all p > 0.05). Among participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all p < 0.05). CONCLUSION: Participants with MHO exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared with those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has the potential to serve as a convenient index for detecting sensitivity to thyroid hormones and further metabolic conditions.

Comparison of six anthropometric measures in discriminating diabetes: A cross-sectional study from the National Health and Nutrition Examination Survey.

BACKGROUND: Traditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating the risk of diabetes. This study aimed to evaluate the performance of new anthropometric measures and a combination of anthropometric measures for identifying diabetes. METHODS: A total of 46 979 participants in the National Health and Nutrition Examination Survey program were included in this study. Anthropometric measures, including weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), and A Body Shape Index (ABSI), were calculated. Logistic regression analysis and restricted cubic splines were used to evaluate the association between the anthropometric indices and diabetes. The receiver operating characteristic (ROC) curve analysis was performed to compare the discrimination of different anthropometric measures. RESULTS: All anthropometric measures were positively and independently associated with the risk of diabetes. After adjusting for covariates, the per SD increment in WC, WtHR, and CI increased the risk of diabetes by 81%, 83%, and 81%, respectively. In the ROC analysis, CI showed superior discriminative ability for diabetes (area under the curve 0.714), and its optimum cutoff value was 1.31. Results of the combined use of BMI and other anthropometric measures showed that among participants with BMI <30 kg/m2 , an elevated level of another metric increased the risk of having diabetes (P < .001). Similarly, at low levels of weight, CI, and ABSI, an elevated BMI increased diabetes risk (P < .001). CONCLUSIONS: WtHR and CI had the best ability to identify diabetes when applied to the US noninstitutionalized population. Anthropometric measures containing WC information could improve the discrimination ability.

Evaluation of the Degree of Agreement of Four Methods for Diagnosing Diabetic Autonomic Neuropathy.

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing's test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing's test, and HRV in diagnosing DAN. Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing's test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(-) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman's correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method. Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing's test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing's test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing's test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing's test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses. Conclusions: COMPASS-31 and Ewing's test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up.

Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima-media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta-analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence. RESULTS: Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima-media thickness (MD -0.06 mm [95% CI -0.88, -0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI -1.88, 6.29], P = .29), the total daily insulin dosage (SMD -0.81 [95% CI -1.25, -0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events. CONCLUSIONS: Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.