Search

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.

We report the observation of enhanced interfacial two-component superconductivity possessing a dominant triplet component in nonmagnetic CoSi 2 /TiSi 2 superconductor/normal-metal planar heterojunctions. This is accomplished through the detection of odd-frequency spin-triplet even-parity Cooper pairs in the diffusive normal-metal component of T-shaped proximity junctions. We show that by modifying the diffusivity of the normal-metal part, the transition temperature enhancement can be tuned by a factor of up to 2.3 while the upper critical field increases by up to a factor of 20. Our data suggest that the C49 phase of TiSi 2 , which is stabilized in confined geometries, underlies this enhancement. These findings are addressed via a Ginzburg-Landau model and the quasi-classical theory. We also relate our findings to the enigmatic 3-K phase reported in Sr 2 RuO 4 .

Introduction: An increasing number of breast cancer survivors (BCS) use traditional Chinese medicine (TCM) throughout their cancer journey. There is emerging evidence that TCM is effective in the reducing side effects of chemotherapy. However, qualitative patient-centric and culturally relevant research into TCM use is scant. This qualitative study aimed to explore the use and perceptions of Chinese Hong Kong BCS using TCM., Methods: Participants were recruited from a university hospital and three breast cancer patient groups in Hong Kong. Questionnaires regarding the use of TCM were given to all participants, followed by individual semi-structured interviews on selected BCS to comprehensively understand TCM's use and perceptions. A greater emphasis was placed on the qualitative data., Results: About half of the participants (n = 67, 48.9%) used TCM during their cancer treatment journey, among which almost all (n = 64, 95.5%) had improved symptoms. Sleeping disturbances (n = 58, 86.6%) and fatigue (n = 53, 79.1%) were the two most common symptoms that improved after TCM. Interview data revealed that participants used TCM to satisfy unmet needs that mainstream conventional Western medicine could not fulfil. They wished for a sense of control and better well-being. They expressed improvements in physical and psychological well-being after the use of TCM. Despite existing barriers, including high cost, long duration of treatment, and disapproval from oncologists, most would still recommend TCM to fellow survivors., Conclusions: Chinese Hong Kong BCS who used TCM reported positive experiences. Understanding how BCS perceive and use TCM is important to integrating TCM into survivorship care in this population., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Two-dimensional (2D) semiconducting monolayers such as transition metal dichalcogenides (TMDs) are promising channel materials to extend Moore's Law in advanced electronics. Synthetic TMD layers from chemical vapor deposition (CVD) are scalable for fabrication but notorious for their high defect densities. Therefore, innovative endeavors on growth reaction to enhance their quality are urgently needed. Here, we report that the hydroxide W species, an extremely pure vapor phase metal precursor form, is very efficient for sulfurization, leading to about one order of magnitude lower defect density compared to those from conventional CVD methods. The field-effect transistor (FET) devices based on the proposed growth reach a peak electron mobility ~200 cm 2 /Vs (~800 cm 2 /Vs) at room temperature (15 K), comparable to those from exfoliated flakes. The FET device with a channel length of 100 nm displays a high on-state current of ~400 µA/µm, encouraging the industrialization of 2D materials., (© 2022. The Author(s).)

Recent studies have identified cancer-associated mutations in histone genes that lead to the expression of mutant versions of core histones called oncohistones. Many oncohistone mutations occur at Asp and Glu residues, two amino acids known to be ADP-ribosylated (ADPRylated) by PARP1. We screened 25 Glu or Asp oncohistone mutants for their effects on cell growth in breast and ovarian cancer cells. Ectopic expression of six mutants of three different core histones (H2B, H3, and H4) altered cell growth in at least two different cell lines. Two of these sites, H2B-D51 and H4-D68, were indeed sites of ADPRylation in wild-type (unmutated) histones, and mutation of these sites inhibited ADPRylation. Mutation of H2B-D51 dramatically altered chromatin accessibility at enhancers and promoters, as well as gene expression outcomes, whereas mutation of H4-D68 did not. Additional biochemical, cellular, proteomic, and genomic analyses demonstrated that ADPRylation of H2B-D51 inhibits p300-mediated acetylation of H2B at many Lys residues. In breast cancer cell xenografts in mice, H2B-D51A promoted tumor growth, but did not confer resistance to the cytotoxic effects of PARP inhibition. Collectively, these results demonstrate that functional Asp and Glu ADPRylation sites on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of post-translational modifications via distinct mechanisms., Significance: This study identifies cancer-driving mutations in histones as sites of PARP1-mediated ADP-ribosylation in breast and ovarian cancers, providing a molecular pathway by which cancers may subvert the growth-regulating effects of PARP1., (©2022 American Association for Cancer Research.)

The demand for health care has increased with the development of global technology and the rise of public health awareness, and smart service systems have also been introduced to medical care to relieve the pressure on hospital staff. However, the survey found that patients' willingness to use smart services at the time of consultation has not improved. The main research purpose of this study was to understand the willingness of patients from various groups to use smart medical service systems and to explore the influencing factors on patients' use of smart service systems in hospitals through the technology acceptance model. This study distributed questionnaires in the outpatient area of National Taiwan University Hospital Yunlin Branch, and a total of 202 valid questionnaires were obtained. After related research and regression analysis, it was found that patients paid more attention to the benefits and convenience brought by smart services. If patients believed that smart services were trustworthy and beneficial to themselves, their usage intention and attitude would be positive. The results of this study are summarized by the following four points: (1) Designed according to the cultural conditions of different regions; (2) think about design from the patient's perspective; (3) strengthen the explanation and promotion of smart services; and (4) add humanized care and design. This study could be used as a reference for hospitals to improve their service quality and systems in the future.