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Background With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. Results In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. Conclusions Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage. Graphical Abstract

Digital health tools, such as websites, now proliferate to assist individuals in managing their health. With user input, we developed the Your Family Connects (YFC) website to promote access to genetic services for survivors of ovarian cancer and their relatives. Although we estimated that half or more would access the website, only 18% of invited survivors did so. We assessed the extent to which perceived relevance of the information provided, trust, and privacy concerns influenced decisions not to access the website. We designed a theory-based cross-sectional survey to explore the following questions: (1) To what extent did nonresponders endorse privacy concerns? (2) Were privacy concerns associated with recall of receiving the website invitation, time since diagnosis, age, and race? (3) Could we identify profiles of nonresponders that would guide the development of future interventions to encourage engagement in health websites for families affected by inherited cancers? A sample of survivors who were eligible to access the website yet did not respond to the study invitation was identified by linking study IDs to the Georgia Cancer Registry information. The survey was brief and contained 27 items, including recall of the invitation, interest in ovarian cancer information, benefits of using health websites, trust in health websites, and trust in university-based health research. We conducted factor analyses, regression analyses, ANOVA, correlation analyses, and logistic regression to address research questions. Of the 650 nonresponders to whom we sent the short survey, 368 (56.3%) responded and provided sufficient data for analysis. The mean response of 2.57 on the trust scale was significantly below the scale midpoint of 3 (t =11.78, P<.001), suggesting that survivors who did not log on were on average distrustful of health websites. Belonging to a racial or ethnic minority group was associated with being more trusting and less skeptical about health websites. Just 196 (30.1%) nonresponders recalled the invitation to visit the website. Logistic regression analysis indicated that age was the only significant predictor of recall. Testing a model with age, racial or ethnic minority status, and the 6 privacy concerns correctly classified 58.8% of nonresponders, a rate of successful classification that was not appreciably better than a logistic regression analysis that included only age as a predictor. The nonresponders in the present study-particularly the White nonresponders-were skeptical of website platforms regardless of whether they recalled receiving a website invitation or not. Social marketing approaches geared toward building trust in web platforms by building a relationship with an information consumer and in collaboration with trusted organizations warrant further investigation. ClinicalTrials.gov NCT04927013; https://clinicaltrials.gov/study/NCT04927013.

Global temperature is projected to increase, which impacts the ecological process in northern mid- and high-latitude ecosystems, but the winter temperature change in ecosystems is among the least understood. Rice paddy represents a significant contributor to global anthropogenic CH 4 emissions and has a strong climate forcing feedback; however, the legacy effects of warming winter on CH 4 emissions in the subsequent growing season remain uncertain. Here, we conducted field and incubation experiments to determine the effects of winter soil temperature changes on CH 4 emissions in the subsequent growing season. First, in the 3 year field experiment, we continuously measured CH 4 emissions from the rice cropping system. The winter soil temperature and its variation showed significant differences over the 3 years. In the warming-winter year, the rice paddy accumulated less NH 4 + –N and more dissolved organic carbon (DOC) in the soil during winter, resulting in high CH 4 emissions. Second, we incubated the paddy soils without flooding at three temperatures (5 °C, 15 °C, and 25 °C) for 4 weeks to simulate warming winter, and subsequently incubated at same temperature (25 °C) under submerged conditions for 4 weeks to simulate growing season. The result was consistent with field experiment, increased soil temperature significantly increased soil DOC content and decreased NH 4 + –N content in ‘winter season’. The CH 4 emissions in the subsequent ‘growing season’ increased by 190% and 468% when previous incubation temperature increased 10 °C and 20 °C. We showed strong and clear links between warming winter and CH 4 emissions in the subsequent growing season for the first time, suggesting that CH 4 related processes respond not only to warming during the growing season but also in the previous winter. Our findings indicate that nonuniform global warming causes a disproportionate increase in climate forcing feedback to emit more CH 4 .

Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage. A novel lnc‐HZ10 suppresses homologous recombination repair of dsDNA break in human trophoblast cells. Lnc‐HZ10 and AhR form a positive feedback loop. AhR suppresses BRCA1 transcription; and lnc‐HZ10 interacts with γ‐H2AX to impair the interactions of γ‐H2AX with BRCA1. AhR/lnc‐HZ10/BRCA1 axis can be considered as a promising target for alleviation of unexplained miscarriage.

Citizen science (CS) approaches involving non-professional researchers (citizens) as research collaborators has been used infrequently in health promotion generally and specifically, in cancer prevention. Standardized CS approaches may be especially useful for developing communication interventions to encourage families to consider cancer genetic services. We engaged survivors of ovarian cancer and their close relatives as CS collaborators to collect and help interpret data to inform content for a website, printed invitation materials, and short-message reminders. We applied an implementation quality framework, and posed four research questions regarding the feasibility of CS: recruitment, data collection, data quality and evaluation of the experience. CS members were recruited through three networks: clinical sites, local and national cancer support organizations, and online ovarian cancer patient support groups. The professional research team operationalized theory-aligned CS tasks, five data collection options, question banks/scripts for creating surveys, structured interviews, online training and ongoing support from research coaches. 14 CS members agreed to the 12-week and 20-hour commitment for an honorarium. CS members opted to do both qualitative and quantitative assessments. CS members collected 261 surveys and 39 structured interviews. The largest number of surveys were collected for Task 1 (n = 102) to assess survivors’ reactions to different possible options for motivating survivors to visit a study website; 77% of this data were complete (i.e., no missing values). Data collected for tasks 2, 3, 4, and 5 (e.g., assessment of survivors’ and relatives’ respective communication preferences) ranged from 10 to 58 surveys (80% to 84% completeness). All data were collected within the specified time frame. CSs reported 17 hours of work on average and regarded the experience positively. Our experience suggests that CS engagement is feasible, can yield comprehensive quantitative and qualitative data, and is achievable in a relatively a short timeline.

Several described growth factors influence the proliferation and regeneration of the intestinal epithelium. Using a transgenic mouse model, we identified a human gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing protein expressed in enteroendocrine cells as well as in epithelial cells in various tissues. Upon injection into mice, the protein induced rapid onset of crypt cell proliferation involving {szligbeta}-catenin stabilization, possibly by a process that is distinct from the canonical Wnt-mediated signaling pathway. The protein also displayed efficacy in a model of chemotherapy-induced intestinal mucositis and may have therapeutic application in gastrointestinal diseases.

R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/β-catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt reporter TOPGAL mice and have identified the oral mucosa as a target tissue for RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation of β-catenin and resulted in increased basal layer cellularity, thickened mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapy-induced oral mucositis in several mouse models. Prophylactic treatment with RSpo1 dose-dependently overcame the reduction of basal layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing basal layer epithelial regeneration and accelerating mucosal repair through up-regulation of Wnt/β-catenin pathway.

Purpose - The purpose of this paper is to explore the effect that a prospective pathway college affiliated to a large comprehensive university in Sydney may have on the university's reputation. In particular, the association of reputation with preference for a pathway college, brand awareness and the opinion of college brand are examined.Design methodology approach - An online survey was conducted in metropolitan Sydney, Australia, and produced 501 questionnaires responses. A correlation study was used to analyse the relationship between variables of preference for college, perceived reputation, brand awareness and opinion of college brand.Findings - The community reacted positively to a prospective college by agreeing that its merit is in providing a second chance for disadvantaged students and added to the diversity profile of the university. Reputation predicted brand awareness, preference for the college and the opinion of the college brand. Teaching quality of the college is found to be the most important factor to enhance the reputation of the university as well as brand.Originality value - The paper explores the difference and relationship between reputation and brand awareness in a higher education context and how this influenced students' decisions. This knowledge has useful implications for higher education management practice.

The Wnt signaling pathway has a crucial role in regulating cell growth and differentiation and is required for tissue homeostasis and repair. Although constitutive activation of the Wnt pathway can lead to abnormal cell growth and cancer, modulation of Wnt signaling might have a therapeutic benefit for tissue regeneration in numerous diseases. Recently, preclinical studies have demonstrated that treatments with antibodies against the Wnt inhibitor Dickkopf1 (DKK1) and with the positive Wnt modulator R-Spondin1 (RSpo1) were sufficient to repair the bone lesions in multiple myeloma and rheumatoid arthritis and to restore the damaged mucosa in experimental colitis, respectively. A remarkable balance is set for Wnt signaling by secreted proteins such as RSpo1 and DKK1, which help to regulate tissue homeostasis. As physiological Wnt response is essential for the regeneration of damaged tissues, modulation of the Wnt pathway might be beneficial for the treatment of multiple human diseases.

A weak character signal with low frequency can be detected based on the mechanism of vibrational resonance (VR). The detection performance of VR is determined by the synergy of a weak low-frequency input signal, an injected high-frequency sinusoidal interference and the nonlinear system(s). In engineering applications, there are many weak fault signals with high character frequencies. These fault signals are usually submerged in strong background noise. To detect these weak signals, an adaptive detection method for a weak high-frequency fault signal is proposed in this paper. This method is based on the mechanics of VR and cascaded varying stable-state nonlinear systems (VSSNSs). Partial background noise with high frequency is regarded as a special type of high-frequency interference and an energy source that protrudes a weak fault signal. In this way, high-frequency background noise is utilized in a VSSNS. To improve the detection ability, manually generated high-frequency interference is injected into another VSSNS. The VSSNS can be transformed into a monostable state, bistable state or tristable state by tuning the system parameters. The proposed method is validated by a simulation signal and industrial applications. The results show the effectiveness of the proposed method to detect a weak high-frequency character signal in engineering problems.