Measles virus is a major public health concern worldwide. Three measles virus cell receptors have been identified so far, and the structures of the first two in complex with measles virus hemagglutinin (MV-H) have been reported. Nectin-4 is the most recently identified receptor in epithelial cells, and its binding mode to MV-H remains elusive. In this study, we solved the structure of the membrane-distal domain of human nectin-4 in complex with MV-H. The structure shows that nectin-4 binds the MV-H β4-β5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions. The binding site in MV-H for nectin-4 also overlaps extensively with those of the other two receptors. Finally, a hydrophobic pocket centered in the β4-β5 groove is involved in binding to all three identified measles virus receptors, representing a potential target for antiviral drugs.
Immune and inflammation dysregulation have been associated with the aging process and contribute to age-related disorders, but the underlying mechanism remains elusive. Here, we employed late-generation Terc knockout (Terc) mice to investigate the impact of telomere dysfunction on the host defense and function of innate immune cells. Terc mice displayed exaggerated lung inflammation and increased mortality upon respiratory staphylococcal infection, although their pathogen-clearing capacity was uncompromised. Mechanistically, we found that telomere dysfunction caused macrophage mitochondrial abnormality, oxidative stress, and hyperactivation of the NLRP3 inflammasome. The ubiquitin-editing enzyme TNFAIP3, together with PGC-1α, was critically involved in the regulation of mitochondrial and inflammatory gene expression and essential for the homeostatic role of telomeres. Together, the study reveals a regulatory paradigm that connects telomeres to mitochondrial metabolism, innate immunity, and inflammation, shedding light on age-related pathologies.
IntroductionThe aim was to compare the efficacy of long-acting and short-acting gonadotropin-releasing hormone (GnRH) agonists by long protocol on embryo quality, endometrial thickness and pregnancy rate in in vitro fertilization.Material and methodsIn this retrospective study, long-term pituitary downregulation, achieved with long- and short-acting GnRH agonists (GnRHa), was performed for patients undergoing in vitro fertilization (n = 175).ResultsThere were no significant differences between the long and short-acting GnRH group (63.16% vs. 66.26%, p > 0.05), and the secondary and primary infertility group (63.47% vs. 66.86%, p > 0.05) in embryo quality. Logistic regression analysis showed that type of infertility and endometrial thickness were significantly associated with pregnancy outcome. Patients in the long-acting GnRHa group had a thicker endometrium on the day of human chorionic gonadotrophin (hCG) administration (10.79 ±2.62 mm vs. 9.64 ±1.97 mm, p < 0.01), lower serum luteinizing hormone (LH) concentration (1.21 ±1.13 vs. 2.53 ±3.39) and a higher pregnancy rate (59.60% vs. 43.42%, p < 0.05) than those of patients in the short-acting GnRHa group.ConclusionsThis work suggests that types of agonist protocol and infertility may not affect embryo quality. Type of infertility and endometrial thickness may be positive predictors for clinical pregnancy, but the key finding is that the long-acting GnRHa protocol may be an effective method of improving endometrial thickness, endometrial receptivity and pregnancy rate in in vitro fertilization.
Cyst formation and enlargement in
autosomal dominant kidney disease
(ADPKD) is mainly driven by aberrantly increased cytosolic cAMP in
renal tubule epithelial cells. Because the vasopressin V2 receptor (V2R) regulates intracellular cAMP levels in
kidneys, a series of benzodiazepine derivatives were developed targeting
the V2R. Among these derivatives, compound 25 exhibited potent binding affinity to the V2R (K
i = 9.0 ± 1.5 nM) and efficacious cAMP
inhibition (IC50 = 9.2 ± 3.0 nM). This led to the
suppression of cyst formation and growth in both an MDCK cell model
and an embryonic kidney cyst model. Further advancing compound 25 in a murine model of ADPKD demonstrated a significantly
improved in vivo efficacy compared with the reference
compound tolvaptan. Overall, compound 25 holds therapeutic
potential for the treatment of ADPKD.
Background: To investigate the effectiveness of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol used in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with endometriosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.