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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. (Contains 2 tables.)

Purpose: This article aims to explore how self-efficacy is related to academic research activities and how intra-culturally relevant factors may play a role in self-efficacy in the context of higher education in Beijing. In particular, relationships of self-efficacy for research with research productivity and idiocentrism-allocentrism are to be examined. Design/methodology/approach: A survey was administered to academics in ten randomly selected universities in Beijing and generated 296 valid questionnaires. Data were analysed using factor analysis and multiple regression. Findings: Gender and discipline are identified as predictors of self-efficacy. Specifically, female academics reported lower levels of self-efficacy for research than males. Academics in the social sciences reported lower levels of self-efficacy for research than those in the natural sciences. Moreover, relationships are also found between self-efficacy for research and idiocentrism-allocentrism. Originality/value: The study makes an extensive investigation of self-efficacy theory, originally developed in Western contexts, in an Eastern culture and provides evidence that intra-cultural and demographic factors play substantial roles in research self-efficacy. (Contains 6 tables.)

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) leads to dysfunctions of human trophoblast cells and further induces miscarriage. In our previous study, we have found that lnc-HZ03 and miR-hz03 are upregulated in BPDE-exposed human trophoblast cells and in recurrent miscarriage tissues; and the upregulated miR-hz03 caused by lnc-HZ03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. However, how lnc-HZ03 upregulates miR-hz03 is completely unknown. In this study, we find that lnc-HZ03 upregulates the expression level of a transcription factor TFIID (a TATA-binding protein) and promotes TFIID-mediated transactivation response element RNA-binding protein (TRBP) transcription. Subsequently, the upregulated TRBP promotes the maturation of miR-hz03 by splicing its precursor pre-miR-hz03 in human trophoblast cells. In BPDE-exposed trophoblast cells or in recurrent miscarriage tissues, lnc-HZ03 was upregulated, which accelerates the TFIID-mediated TRBP transcription and thus promotes TRBP-mediated miR-HZ03 maturation. Subsequently, the upregulated miR-hz03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. This work provides new insights into the regulation of miRNA expression levels by lncRNAs in BPDE-exposed human trophoblast cells. [ABSTRACT FROM AUTHOR]

Introduction: Encouraging family communication about possible genetic risk has become among the most important avenues for achieving the full potential of genomic discovery for primary and secondary prevention. Yet, effective family-wide risk communication (i.e., conveying genetic risk status and its meaning for other family members) remains a critical gap in the field. We aim to describe the iterative process of developing a scalable population-based communication outreach intervention, Your Family Connects, to reach ovarian cancer survivors and close relatives to communicate the potential for inherited risk and to consider genetic counseling. Methods: Relational-level theories (e.g., interdependence theory) suggest that interventions to promote family cancer risk communication will be most effective if they consider the qualities of specific relationships and activate motives to preserve the relationship. Informed by these theories, we collaborated with 14 citizen scientists (survivors of ovarian cancer or relatives) and collected 261 surveys and 39 structured interviews over 12 weeks of citizen science activities in 2020. Results: The citizen science findings and consideration of relational-level theories informed the content and implementation of Your Family Connects (www.yourfamilyconnects.org). CS results showed survivors favor personal contact with close relatives, but relatives were open to alternative contact methods, such as through health professionals. Recognizing the need for varied approaches based on relationship dynamics, we implemented a relative contact menu to enable survivors identify at-risk relatives and provide multiple contact options (i.e., survivor contact, health professional contact, and delayed contact). In line with relational autonomy principles, we included pros and cons for each option, assisting survivors in choosing suitable contact methods for each relative. Discussion: Our developed intervention represents a novel application of relational-level theories and partnership with citizen scientists to expand genetic services reach to increase the likelihood for fair distribution of cancer genomic advances. The Your Family Connects intervention as part of a randomized trial in collaboration with the Georgia Cancer Registry compared with standard outreach. [ABSTRACT FROM AUTHOR]

Early embryonic lung branching morphogenesis is regulated by many growth factor-mediated pathways. Bone morphogenetic protein 4 (BMP4) is one of the morphogens that stimulate epithelial branching in mouse embryonic lung explant culture. To further understand the molecular mechanisms of BMP4-regulated lung development, we studied the biological role of Smad-ubiquitin regulatory factor 1 (Smurf1), an ubiquitin ligase specific for BMP receptor-regulated Smads, during mouse lung development. The temporo-spatial expression pattern of Smurf1 in mouse embryonic lung was first determined by quantitative real-time PCR and immunohistochemistry. Overexpression of Smurf1 in airway epithelial cells by intratracheal introduction of recombinant adenoviral vector dramatically inhibited embryonic day (E) 11.5 lung explant growth in vitro. This inhibition of lung epithelial branching was restored by coexpression of Smad1 or by addition of soluble BMP4 ligand into the culture medium. Studies at the cellular level show that overexpression of Smurf1 reduced epithelial cell proliferation and differentiation, as documented by reduced PCNA-positive cell index and by reduced mRNA levels for surfactant protein C and Clara cell protein 10 expression. Further studies found that overexpression of Smurfl reduced BMP-specific Smad1 and Smad5, but not Smad8, protein levels. Thus overexpression of Smurf1 specifically promotes Smad1 and Smad5 ubiquitination and degradation in embryonic lung epithelium, thereby modulating the effects of BMP4 on embryonic lung growth. lung development; bone morphogenetic protein; Smad-ubiquitin regulatory factor 1

Tumor necrosis factor-[alpha] converting enzyme (TACE) is a membrane-anchored, Zn-dependent metalloprotease, which belongs to the ADAM (a disintegrin and metalloprotease) family. TACE functions as a membrane sheddase to release the ectodomain portions of many transmembrane proteins, including the precursors of TNF[alpha] , TGF[alpha], several other cytokines, as well as the receptors for TNF[alpha], and neuregulin (ErbB4). Mice with [TACE.sup.[delta]Zn/[delta]Zn] null mutation die at birth with phenotypic changes, including failure of eyelid fusion, hair and skin defects, and abnormalities of lung development. Abnormal fetal heart development was not previously described. Herein, we report that [TACE.sup.[delta]Zn/[delta]Zn] null mutant mice by late gestation exhibit markedly enlarged fetal hearts with increased myocardial trabeculation and reduced cell compaction, mimicking the pathological changes of noncompaction of ventricular myocardium. In addition, larger cardiomyocyte cell size and increased cell proliferation were observed in ventricles of [TACE.sup.[delta]Zn/[delta]Zn] knockout mouse hearts. At the molecular level, reduced expression of epidermal growth factor receptor, attenuated protein cleavage of ErbB4, and changes in MAPK activation were also detected in [TACE.sup.[delta]Zn/[delta]Zn] knockout heart tissues. The data suggest that TACE-mediated cell surface protein ectodomain shedding plays an essential and a novel regulatory role during cardiac development and modeling. Keywords: TACE; Heart development; Cardiomyocyte

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. [ABSTRACT FROM AUTHOR]

Transforming growth factor-[beta] (TGF-[beta]) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-[beta] signals from the cell membrane to the nucleus. Using mice without Smad3 gene expression, we investigated whether Smad3 could regulate bleomycin-induced pulmonary fibrosis in vivo. Mice deficient in Smad3 demonstrated suppressed type I procollagen mRNA expression and reduced hydroxyproline content in the lungs compared with wild-type mice treated with bleomycin. Furthermore, loss of Smad3 greatly attenuated morphological fibrotic responses to bleomycin in the mouse lungs, suggesting that Smad3 is implicated in the pathogenesis of pulmonary fibrosis. These results show that Smad3 contributes to bleomycin-induced lung injury and that Smad3 may serve as a novel target for potential therapeutic treatment of lung fibrosis. transforming growth factor-[beta]; hydroxyproline

Molecular embryology of the lung is a relatively young field. Since 1992, however, much progress has been made in establishing the molecular basis for cell lineage differentiation and embryonic lung morphogenesis. Advances in this area include insights into gain- versus loss-of-function phenotypes of specific genes and gene families and findings regarding the conservation of functions between genes that regulate morphogenesis. As a result of such advances, the development of new therapeutic methods for pulmonary problems such as dysplasia has been accelerated.

Research was conducted to examine the effects of nicotine on murine lung development utilizing a serumless mouse lung culture system. A total RNA isolation kit was utilized to determine total RNA from cultured lungs in guanidinium thiocyanate while quantification was carried out by densitometric band scanning. Results indicated that nicotine exposure influences branching morphogenesis and suggested a direct, local effect on the developing lungs of tobacco smoke-exposed fetuses.

Research shows that the genetic expression of matrix gla protein (MGP) in early embryonic mouse lung culture is more pronounced in the presence of exogenous transforming growth factor-beta1 (TGF-beta1). MGP messenger ribonucleic acid expression under the influence of TGF-beta1 changes over time and in varying concentrations of TGF-beta1. Experimental evidence suggests that MGP may play a crucial role in lung morphogenesis, possibly via endogenous TGF-beta signaling.

TGF-[Beta]1 is a known inhibitor of branching morphogenesis when added exogenously to mouse embryonic lungs in culture. However, the issue of whether endogenous TGF-[Beta] signaling has a function in the process of lung organogenesis is not completely resolved. We utilized immunoperturbation and antisense oligodeoxynucleotide inhibitory strategies to abrogate TGF-[Beta] type II receptor function in embryonic mouse lungs undergoing branching morphogenesis in serumless explant culture. Antisera directed against a TGF-[Beta] type II receptor N-terminal peptide that perturbs TGF-[Beta] ligand-receptor binding increased branching by 70%. Similarly, antisense TGF-[Beta] type II receptor oligodeoxynucleotides (40/[[micro]molar]) resulted in a 58% increase in branching, compared to scrambled and mismatched sequence controls, while TGF-[Beta] type II receptor mRNA and its protein expression levels were suppressed by 95 and 84%, respectively. Addition of exogenous TGF-[Beta]1 did not overcome the stimulatory effects either of TGF-[Beta] type II receptor immunoperturbation or of antisense oligodeoxynucleotide treatment on lung branching morphogenesis. Using in situ hybridization and immunohistochemistry, both TGF-[Beta] type II receptor mRNA and protein were localized to the epithelium lining the developing airways, and to the surrounding mesenchyme, indicating that TGF-[Beta] type II receptor is an important regulator of epithelial-mesenchymal interaction. Exogenous TGF-[Beta]1 decreased cyclin A mRNA levels in control embryonic lung explants, while TGF-[Beta] type II receptor antisense oligodeoxynucleotides prevented the downregulation of cyclin A mRNA expression by exogenous TGF-[Beta]1. In addition, PCNA immunostaining of the primitive bronchial epithelium was increased in the presence of TGF-[Beta] type II receptor antisense oligodeoxynucleotides either alone or together with exogenous TGF-[Beta]1, whereas TGF-[Beta]1 alone decreased PCNA staining. Thus, abrogation of TGF-[Beta] type II receptor expression prevented TGF-[Beta]1-induced epithelial cell [G.sub.1] arrest. These results demonstrate, for the first time, that abrogation of the TGF-[Beta] type II receptor stimulates embryonic lung organogenesis in culture and reverses the negative influence of endogenous TGF-[Beta] signaling upon epithelial cell cycle progression.

Objective: To explore the potential regulation mechanisms of miR-384-5p in Neuropathic pain (NP). Methods: Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using Withdrawal Threshold (PWT) and Paw Withdrawal Latency (PWL). qPCR and Western blotting were used to determine the relative expression of miR-384-5p and SCN3A. The inflammation response in spinal microglia cells was determined by ELISA assay. Immunofluorescence assay was used to demonstrate the co-localization of miR-384-5p with SCN3A in rat dorsal root ganglions (DRGs). The target genes of miR-384-5p were verified by dual-luciferase report assays. Results: In the current study, the miR-384-5p expression level was significantly downregulated in CCI rats when comparing to the sham group. In addition, miR-384-5p agomir significantly repressed mechanical allodynia and heat hyperalgesia in CCI rats. Meanwhile, the current study indicated miR‐384‐5p could decrease inflammation progress in spinal microglia cells incubated in lipopolysaccharide. Consistently, overexpression of miR-384-5p obviously depressed inflammation cytokine levels in CCI rats. Dual-luciferase reporter assays indicated that SCN3A is a target gene of miR-384-5p. Conclusion: miR-384-5p is a negative regulator in the development of neuropathic pain by regulating SCN3A, indicating that miR-384-5p might be a promising therapeutic target in the treatment of neuropathic pain. Abbreviations: CCI: Chronic constriction injury; ZEB1: Zinc finger E box binding protein-1; MAPK6: Mitogen-activated protein kinase 6; COX-2: cyclooxygenase-2. [ABSTRACT FROM AUTHOR]

• Beside the main phase of zincblende, a small amount of wurtzite is existed in CVD ZnS. • The mechanical properties of CVD ZnS were characterized with a slight variation of Zn/S ratio. • Zn 46.84 S 53.16 presents a high flexural strength of 133.8 MPa. • XRD, SEM, and Raman spectra of CVD ZnS were conducted. Polycrystalline ZnS samples with a slight composition fluctuation are grown by chemical vapor deposition (CVD) method, and their optical and mechanical properties and microstructure were investigated in detail. The CVD samples present a maximum transmittance of ∼73% in the 7–10 μm region. By changing the sulfur content, a maximum Knoop hardness of 2.375 GPa was found in the Zn 50.06 S 49.94 sample, while Zn 46.84 S 53.16 presents a high flexural strength of 133.8 MPa. The microstructural origin of this abnormal changing of mechanical properties was discussed according to the results of micrographs, XRD patterns and Raman spectra. The results suggest that beside the main phase of zincblende, a small amount of wurtzite is existed. This composited microstructure is responsible for the higher hardness and strength of CVD ZnS. [ABSTRACT FROM AUTHOR]

Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol 280: L1030-L1039, 2001.--Bone morphogenetic protein-4 (BMP-4) is a key morphogen for embryonic lung development that is expressed at high levels in the peripheral epithelium, but the mechanisms that modulate BMP-4 function in early mouse lung branching morphogenesis are unclear. Here, we studied the BMP-4 antagonist Gremlin, which is a member of the DAN family of BMP antagonists that can bind and block BMP-2/4 activity. The expression level of gremlin in embryonic mouse lungs is highest in the early embryonic pseudoglandular stage [embryonic days (E) 11.5-14.5] and is reduced during fetal lung maturation (E18.5 to postnatal day 1). In situ hybridization indicates that gremlin is diffusely expressed in peripheral lung mesenchyme and epithelium, but relatively high epithelial expression occurs in branching buds at E11.5 and in large airways after E16.5. In E11.5 lung organ culture, we found that exogenous BMP-4 dramatically enhanced peripheral lung epithelial branching morphogenesis, whereas reduction of endogenous gremlin expression with antisense oligonucleotides achieved the same gain-of-function phenotype as exogenous BMP-4, including increased epithelial cell proliferation and surfactant protein C expression. On the other hand, adenoviral overexpression of gremlin blocked the stimulatory effects of exogenous BMP-4. Therefore, our data support the hypothesis that Gremlin is a physiologically negative regulator of BMP-4 in lung branching morphogenesis. bone morphogenetic protein; lung development; organogenesis