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Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explored the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild-type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln modulates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation of ERα on serine 118 (S118), as well as by reducing the E2-dependent binding of ERα across the genome. These effects were associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of some genes and enhanced expression of others. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

ADP-ribosylation (ADPRylation) is a post-translational modification (PTM) of proteins mediated by the activity of a variety of ADP-ribosyltransferase (ART) enzymes, such as the Poly (ADP-ribose) Polymerase (PARP) family of proteins. This PTM is diverse in both form and biological functions, which makes it a highly interesting modification, but difficult to study due to limitations in reagents available to detect the diversity of ADPRylation. Recently we developed a set of recombinant antibody-like ADP-ribose (ADPR) binding proteins using naturally occurring ADPR binding domains (ARBDs), including macrodomains and WWE domains, functionalized by fusion to the constant "Fc" region of rabbit immunoglobulin. Herein, we present an expansion of this biological toolkit, where we have replaced the rabbit Fc sequence with the sequence from two other species, mouse and goat. These new reagents are based on a previously characterized set of naturally occurring ARBDs with known specificity. Characterization of the new reagents demonstrates that they can be detected in a species-dependent manner by secondary immunological tools, recognize specific ADPR moieties, and can be used for simultaneous detection of mono ADPR and poly ADPR at single-cell resolution in various antibody-based assays. The expansion of this toolkit will allow for more multiplexed assessments of the complexity of ADPRylation biology in many biological systems., Competing Interests: Conflict of interest W. L. Kraus is a founder, consultant, and Science Advisory Board member for ARase Therapeutics, Inc. W. L. Kraus is a co-holder of U.S. Patent 9,599,606 covering the ADPR detection reagents described herein. The rabbit ARBD-Fc fusions have been licensed to and are sold by EMD Millipore., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explored the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild-type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln modulates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation of ERα on serine 118 (S118), as well as by reducing the E2-dependent binding of ERα across the genome. These effects were associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of some genes and enhanced expression of others. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes., Competing Interests: Disclosure Summary The authors having no conflicts to disclose. Conflict of Interest The authors have nothing to declare.

Smoking has multiple negative effects on health; therefore, the Taiwanese government provides smoking cessation clinics to smokers. This study aimed to explore the trajectory of smoking cessation after smokers received treatment and the variables related to different trajectories. A retrospective longitudinal study was conducted, in which 735 adult smokers who received smoking cessation medications were recruited. The participants' demographic characteristics, chronic diseases, smoking characteristics, and cigarette dependence were collected from chart review. The amount of smoking was collected at baseline, and at 1 week, 1 month, 3 months, and 6 months after treatment. The Proc Traj procedure for group-based modeling and multinomial logistic regression were used for statistical analysis. Three trajectories were identified: early quitters (28.03%), late quitters (11.43%) and reducers (60.54%). Compared with early quitters, reducers were younger and had a higher probability of severe cigarette dependence. Compared with early quitters, late quitters had a higher number of taking smoking cessation medications. The findings revealed that approximately 60% of participants who received smoking cessation treatment could not completely quit smoking, and that age, number of medications taken, and cigarette dependence were significant predictors of different trajectories., (© 2024. The Author(s).)

Two-dimensional (2D) transistors are promising for potential applications in next-generation semiconductor chips. Owing to the atomically thin thickness of 2D materials, the carrier scattering from interfacial Coulomb scatterers greatly suppresses the carrier mobility and hampers transistor performance. However, a feasible method to quantitatively determine relevant Coulomb scattering parameters from interfacial long-range scatterers is largely lacking. Here, we demonstrate a method to determine the Coulomb scattering strength and the density of Coulomb scattering centers in InSe transistors by comprehensively analyzing the low-frequency noise and transport characteristics. Moreover, the relative contributions from long-range and short-range scattering in the InSe transistors can be distinguished. This method is employed to make InSe transistors consisting of various interfaces a model system, revealing the profound effects of different scattering sources on transport characteristics and low-frequency noise. Quantitatively accessing the scattering parameters of 2D transistors provides valuable insight into engineering the interfaces of a wide spectrum of ultrathin-body transistors for high-performance electronics.