Time-restricted feeding improves metabolic and endocrine profiles in mice with polycystic ovary syndrome

ObjectivesPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathy disorders in premenopausal women, which is characterized by hyperandrogenemia, anovulation, and polycystic ovarian morphology (PCOM). Time-restricted feeding (TRF) is a new intermittent restriction dietary pattern, which has been shown to have positive benefits on obesity and glycolipid metabolism disorders. We aimed to explore the effect of the feeding regimen (ad libitum vs. TRF) on the glycolipid metabolism and reproductive endocrine disorders in a PCOS mouse model.MethodsPCOS mouse model was induced by continuous subcutaneous administration of dihydrotestosterone for 21 days. Mice were fed a high-fat diet (HFD) for 8 weeks on an ad libitum or time- restricted diet (from 10:30 p.m. to 6:30 a.m.).ResultsCompared to control mice, PCOS mice that received TRF treatment had significantly lower body weight, reduced adiposity, lower area under the curve (AUC) of glucose response in the oral glucose tolerance test (OGTT), and lower AUC in the insulin tolerance test (ITT). TRF also ameliorated lipid metabolism, as shown by a reduction in plasma lipid profiles (triglycerides and cholesterol) and the triglyceride content in the liver of PCOS mice. In terms of reproduction, the plasma androgen level, plasma estrogen (E2) level, and luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in PCOS mice were significantly reduced after 8 weeks of TRF treatment. In addition, ovarian histology showed that TRF inhibits cyst formation and promotes corpus luteum formation.ConclusionIn conclusion, TRF improved metabolic and endocrine profiles in mice with PCOS

Chiral <i>N</i>,<i>N</i>′‑Dioxide Organocatalyzed Asymmetric Electrophilic α‑Cyanation of β‑Keto Esters and β‑Keto Amides

An enantioselective electrophilic α-cyanation of 1-indanone-derived β-keto esters and β-keto amides using a hypervalent iodine as the cyanide-transfer reagent was realized. A chiral <i>N</i>,<i>N</i>′-dioxide was used as the efficient bifunctional organocatalyst in the presence of inorganic base, which gave the corresponding α-cyano dicarbonyl compounds in yields of 50–99% with good enantioselectivities (87–97% ee)

Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge.

Small molecule distribution coefficients between immiscible nonaqueuous and aqueous phases-such as cyclohexane and water-measure the degree to which small molecules prefer one phase over another at a given pH. As distribution coefficients capture both thermodynamic effects (the free energy of transfer between phases) and chemical effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodynamic and chemical accuracy of physical models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive physical models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water-saturated octanol phases, since it has greatly reduced water content and a homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we collected cyclohexane/water distribution coefficients for a set of 53 druglike compounds at pH 7.4. These measurements were used as the basis for the SAMPL5 Distribution Coefficient Challenge, where 18 research groups predicted these measurements before the experimental values reported here were released. In this work, we describe the experimental protocol we utilized for measurement of cyclohexane-water distribution coefficients, report the measured data, propose a new bootstrap-based data analysis procedure to incorporate multiple sources of experimental error, and provide insights to help guide future iterations of this valuable exercise in predictive modeling

Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge.

Small molecule distribution coefficients between immiscible nonaqueuous and aqueous phases-such as cyclohexane and water-measure the degree to which small molecules prefer one phase over another at a given pH. As distribution coefficients capture both thermodynamic effects (the free energy of transfer between phases) and chemical effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodynamic and chemical accuracy of physical models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive physical models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water-saturated octanol phases, since it has greatly reduced water content and a homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we collected cyclohexane/water distribution coefficients for a set of 53 druglike compounds at pH 7.4. These measurements were used as the basis for the SAMPL5 Distribution Coefficient Challenge, where 18 research groups predicted these measurements before the experimental values reported here were released. In this work, we describe the experimental protocol we utilized for measurement of cyclohexane-water distribution coefficients, report the measured data, propose a new bootstrap-based data analysis procedure to incorporate multiple sources of experimental error, and provide insights to help guide future iterations of this valuable exercise in predictive modeling

Adenovirus-associated acute conjunctivitis in Beijing, China, 2011–2013

Abstract Background Human adenovirus (HAdV)-associated acute conjunctivitis is a common infectious disease and causes significant morbidity among residents in Beijing, China. However, little is known about the epidemiology and type distribution of acute adenoviral conjunctivitis in Beijing. Methods Acute conjunctivitis surveillance was conducted in 18 hospitals in Beijing from July through October during 2011–2013. HAdVs were detected by PCR from eye swab and types were determined by partial hexon and fiber gene sequencing. Risk factors associated with adenoviral conjunctivitis were analyzed. Results Of 876 conjunctivitis cases, 349 (39.8%) were HAdV positive. HAdV detection was most common in conjunctivitis patients aged 18–40 years; patients with contact history with a conjunctivitis case; patients with specimen collected on days 4–6 post symptom onset and patients who worked in food service as catering attendants. Fifteen types were identified among adenoviral conjunctivitis cases. Five HAdV types (HAdV-4, − 37, − 53, − 64 and − 8) accounted for 81.1% of all adenoviral conjunctivitis cases. HAdV-37, − 4 and − 53 were the most common types associated with adenoviral conjunctivitis in 2011, 2012 and 2013, respectively. Conclusion Multiple HAdV types were associated with acute conjunctivitis in Beijing. Predominant types associated with adenoviral conjunctivitis circulating in Beijing varied from year to year