Discovery of 1,4-Disubstituted Cyclohexene Analogues as Selective GPR119 Agonists for the Treatment of Type 2 Diabetes.

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.

Age at Menopause and Development of Type 2 Diabetes in Korea.

Importance: There is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D).

Objective: To investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women.

Design, Setting, And Participants: This population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009.

Tear film lipid layer thickness and blink dynamics in patients with blepharospasm.

Background: This study investigates the effect of botulinum toxin A on lipid layer thickness (LLT) and blink dynamics in patients with benign essential blepharospasm (BEB) compared to dry eye disease (DED) patients.

Methods: We reviewed the medical records of patients with dry eye disease (DED) and BEB treated with botulinum toxin A (BoT A) injections. Data on demographics, lipid layer thickness (LLT), meiboscore, and blink dynamics measured using a LipiView II interferometer before and 2 months after BoT A were collected.

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.