Highlights d IRE1a deletion in NOD b cells before insulitis causes their transient dedifferentiation d Dedifferentiated b cells show diminished expression of b cell autoantigens d Knockout mice exhibit impaired T cell diabetogenic activity d IRE1a-deficient NOD mice are protected from autoimmune destruction and diabetes

No abstract

An iron-based catalytic system was developed for the cross-coupling of 1-bromoalkynes with terminal alkynes to selectively generate unsymmetrical 1,3-butadiynes in water under air. It was found that a combination of 1-bromoalkynes derived from less acidic terminal alkynes with more acidic counterparts would greatly enhance yields and selectivity for unsymmetrical 1,3butadiynes. The reaction was also applicable for the synthesis of unsymmetrical 1,3,5-hexatriynes through coupling of 1-bromoalkynes and trimethylsilyl-protected 1,3-butadiynes in a one-pot manner.

Introduction The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus–pituitary–gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism. Methods This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change. Results Overall, the patients’ T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use. Conclusions Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.