SUMO-specific proteases: SENPs in oxidative stress-related signaling and diseases.

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.

Blastocyst-Derived Lactic Acid May Regulate S100A6 Expression and Function in Mouse Decidualization via Stimulation of Uterine Epithelial Arachidonic Acid Secretion.

(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.

Adsorption Mechanism of Benzene Derivatives by Pagoda[n]arenes.

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment. The control of these substances has become an important subject of scientific research. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing pagoda[n]arene based supramolecular materials. Density functional theory calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes (Pa[4]As and Pa[5]As). Results indicate that Pa[4]As and Pa[5]As can effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]As possess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivatives to desorb from the adsorbing aggregates, and thus the material can be reutilized.

Effect of Aurora kinase B on polyploidy and decidualization in mouse uterus.

RESEARCH QUESTION: Decidualization is critical to the establishment of mouse normal pregnancy. The fibroblast-like stromal cells in the process form polyploid multinucleated cells. Aurora kinase B (Aurora B) has previously been shown to regulate polyploidy in various cells. However, whether Aurora B regulates the formation of decidual cell polyploidization and its regulatory mechanisms remain poorly understood. DESIGN: Establish decidualization model of mouse primary endometrial stromal cells in vitro. Construct pseudopregnancy mouse models and delayed-activation mouse models. Detect Aurora B and polyploidization related genes in mouse uteri treated by Aurora B specific inhibitor Barasertib and CPT. RESULTS: In this study, we found that Aurora B was strongly expressed in endometrial stromal cells after implantation. Additionally, Aurora B was remarkably up regulated in the stromal cells of oil-induced deciduomoa and in vitro decidualization. As an Aurora B specific inhibitor, Barasertib significantly inhibits the mRNA expression of Prl8a2, a marker of mouse decidualization. Furthermore, the protein levels of p-Plk1, Survivin and p-Cdk1 were inhibited by Barasertib. CPT-induced DNA damage suppressed Aurkb (encodes Aurora B) expression, thus resulting in polyploidization. CONCLUSION: Our data shows that Aurora B is expressed in decidual stromal cells of implantation sites and plays a key role for mouse decidualization. The protein of Plk1, Survivn, and Cdk1 may participate in formation of decidual cell polyploidization during mouse decidualization.

Embryo-derive TNF promotes decidualization via fibroblast activation.

Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI2 and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI2-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.

Ag microlabyrinth/nanoparticles coated large-area thin PDMS films as flexible and transparent SERS substrates for in situ detection.

Flexible and transparent surface-enhanced Raman scattering (SERS) substrates haveattractedmuchattention as a fast, sensitive and in situ detection platform for practical applications. However, the large-area fabrication of flexible and transparent SERS substrates with high performance is still challenging. Here, a flexible and transparent SERS substrate based on large-area thin PDMS film decorated with Ag microlabyrinth/nanoparticles hierarchical structures (denoted as ALNHS@PDMS) is fabricated by using the floating-on-water method and magnetron sputtering technology. By optimizing the sputtering time, the ALNHS with multiple hot spots are uniformly distributed on the PDMS surface. Based on characterizing the rhodamine 6G (R6G) with a portable Raman spectrometer, the optimal ALNHS@PDMS film exhibits a high enhancement factor (5.2 × 106), excellent uniformity and reproducibility, as well as superior mechanical stability. In addition, thanks to the good sticky feature and bi-directional activation property of the thin ALNHS@PDMS film, the prepared flexible and transparent SERS substrate can achieve in situ detection of malachite green residues (10-6 M) on apple and tomato skins. This large-area, thin, mechanically robust, flexible and transparent ALNHS@PDMS film, integrated with a portable Raman spectrometer, shows great potential for point-of-care testing (POCT)in practical applications.

Versatile flexible SERS substrate for in situ detection of contaminants in water and fruits based on Ag NPs decorated wrinkled PDMS film.

Flexible surface-enhanced Raman spectroscopy (SERS) substrate has attracted great attention due to its convenient sampling and on-site monitoring capability. However, it is still challenging to fabricate a versatile flexible SERS substrate, which can be used for in situ detection of analytes either in water or on irregular solid surfaces. Here, we report a flexible and transparent SERS substrate based on a wrinkled polydimethylsiloxane (PDMS) film obtained by transferring corrugated structures on the aluminium/polystyrene bilayer film, onto which silver nanoparticles (Ag NPs) are deposited by thermal evaporation. The as-fabricated SERS substrate exhibits a high enhancement factor (∼1.19×105), good signal uniformity (RSD of 6.27%), and excellent batch-to-batch reproducibility (RSD of 7.3%) for rhodamine 6 G. In addition, the Ag NPs@W-PDMS film can maintain high detection sensitivity even after mechanical deformations of bending or torsion for 100 cycles. More importantly, being flexible, transparent, and light, the Ag NPs@W-PDMS film can both float on the water surface and conformally contact with the curved surface for in situ detection. The malachite green in aqueous environment and on apple peel can be easily detected down to 10-6 M with a portable Raman spectrometer. Therefore, it is expected that such a versatile flexible SERS substrate has great potential in on-site, in situ contaminant monitoring for realistic applications.

Ag NPs@PDMS nanoripple array films as SERS substrates for rapid in situ detection of pesticide residues.

The large-area fabrication of flexible and transparent surface-enhanced Raman scattering (SERS) substrates with high performance by a facile and efficient method is still challenging. Here, we demonstrated a large-scale, flexible and transparent SERS substrate composed of PDMS nanoripple array film decorated with silver nanoparticles (Ag NPs@PDMS-NR array film) prepared by a combination of plasma treatment and magnetron sputtering. The performances of SERS substrates were characterized by rhodamine 6G (R6G) using a handheld Raman spectrometer. The optimal Ag NPs@PDMS-NR array film exhibited high SERS sensitivity, with a detection limitation of R6G reaching 8.20 × 10-8 M as well as excellent uniformity (RSD = 6.8%) and batch-to-batch reproducibility (RSD = 2.3%). In addition, the substrate showed outstanding mechanical stability and good SERS enhancement by backside illumination, thus it was suitable for in situ SERS detection on curved surfaces. The detection limit of malachite green on apple and tomato peels was 1.19 × 10-7 and 1.16 × 10-7 M, respectively, and quantitative analysis of pesticide residues could be realized. These results demonstrate that the Ag NPs@PDMS-NR array film has great practical potential in rapid in situ detection of pollutants.

Human capital space: a spatial perspective of the dynamics of people and economic relationships.

While researchers increasingly recognise drastic changes in populations and repeatedly emphasise their implications for development, far less attention is devoted to thinking of and making spaces available for people. This article proposes the concept of human capital space (HCS) and elaborates on its typology, spatial externalities, selection-sorting-matching mechanism, and crucial role in building dynamic capabilities in cities and regions. Theoretical discourses and constructs furnish reasons to believe that HCS is a useful instrument to examine the complex people-space relationship and to encourage conversations about the interactions among population, labour, economic geographies, and related disciplines. HCS provides a terrain for scientists to actively engage in human-centred spatial development, inform policies in a timely manner, and argue for effective investment in space to bolster the endogenous power of spatial development.

The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization.

Introduction: High-mobility group box 1 (HMGB1) is a non-histone nuclear protein and can be extracellularly secreted to induce sterile inflammation. Although uterine deletion of HMGB1 causes implantation and decidualization defects, how secreted HMGB1 is involved in mouse early pregnancy is still unknown. Methods: Mouse models, mouse primary endometrial cells and human endometrial cell lines were used in this study. Both immunofluorescence and Western blot were performed to show the localization and relative level of HMGB1 and acetylated HMGB1, respectively. Relative mRNA levels were analyzed by real time RT-PCR. Results: The secreted HMGB1 was detected in uterine lumen fluid in mouse periimplantation uterus. There is an obvious difference for secreted HMGB1 levels in uterine fluid between day 4 of pregnancy and day 4 of pseudopregnancy, suggesting the involvement of blastocysts during HMGB1 secretion. Trypsin is clearly detected in mouse blastocyst cavity and in the supernatant of cultured blastocysts. Trypsin significantly stimulates HB-EGF production through activating PAR2 and ADAM17. Uterine injection of PAR2 inhibitor into day 4 pregnant mice significantly reduces the number of implantation sites. HB-EGF released from luminal epithelium can induce mouse in vitro decidualization. The conditioned medium collected from trypsin-treated luminal epithelium is able to induce in vitro decidualization, which is suppressed by EGFR inhibitor. Intrauterine injection of glycyrrhizin (HMGB1 inhibitor) can significantly inhibit mouse embryo implantation. We also showed that exogenous HMGB1 released from human epithelial cells are able to induce human in vitro decidualization. Conclusion: Trypsin can induce decidualization of stromal cells via PAR2-HMGB1-ADAM17-HB-EGF from luminal epithelium.

METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis.

OBJECTIVES: Accumulating evidence suggested that the laminin γ2 (LAMC2) expression level was upregulated in various cancers. However, the potential prognostic value of LAMC2 in cancers remains unclear. We conducted a meta-analysis to clarify the association of LAMC2 expression with prognosis. DESIGN: We searched Embase, Web of Science and PubMed (up to 25 November 2021) to collect all eligible studies, and meta-analysis was performed to interpret the association of LAMC2 expression with clinicopathological parameters, overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). ELIGIBILITY CRITERIA FOR INCLUDING STUDIES: We included studies that investigate the relationship between LAMC2 and prognosis of cancers, patients were divided into two groups, and associations of LAMC2 expression with clinicopathological features were described. RESULTS: Seven studies were finally included. We found that increased LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p<0.001), tumour-node-metastasis stages (log OR: 0.95, 95% CI 0.39 to 1.50, p<0.001) and tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p<0.001), but not with age (log OR -0.05, 95% CI -0.37 to 0.27, p=0.75) or gender (log OR -0.07, 95% CI -0.52 to 0.38, p=0.75). In addition, higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS (HR 1.85, 95% CI 1.31 to 2.40, p<0.001). A similar result was found in The Cancer Genome Atlas database. High LAMC2 expression was significantly associated with OS in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, neck squamous cell carcinoma and brain lower grade glioma. CONCLUSION: Our results suggested that higher LAMC2 expression was correlated with worse survival, lymph node metastasis, tumour-node-metastasis stages and tumour status. This study was subject to inherent limitations, but the results presented here provide insights regarding the potential use of LAMC2 as a biomarker for human cancer. STUDY REGISTRATION: researchregistry.com (researchregistry1319).

3D Flexible SERS Substrates Integrated with a Portable Raman Analyzer and Wireless Communication for Point-of-Care Application.

With the development of flexible surface-enhanced Raman spectroscopy (SERS) substrates that can realize rapid in situ detection, the SERS technique accompanied by miniaturized Raman spectrometers holds great promise for point-of-care testing (POCT). For an in situ detection strategy, constructing high-performance flexible and transparent SERS substrates through a facile and cost-effective fabrication method is critically important. Herein, we present a simple method for fabricating a large-area flexible and transparent SERS substrate consisting of a silver-nanoparticle-grafted wrinkled polydimethylsiloxane (Ag NPs@W-PDMS) film, using a surface-wrinkling technique and magnetron sputtering technology. By characterizing rhodamine 6G as a probe molecule with a portable Raman spectrometer, the flexible SERS substrate shows a low detection limit (10-7 M), a high enhancement factor (6.11 × 106), and excellent spot-spot and batch-batch reproducibilities (9.0% and 4.2%, respectively). Moreover, the Ag NPs@W-PDMS substrate maintains high SERS activity under bending and twisting mechanical deformations of over 100 cycles, as well as storage in air for 30 days. To evaluate its practical feasibility, in situ detection of malachite green on apple and tomato peels is performed with a detection limit of 10-6 M. In addition, for point-of-care analysis, we develop a wireless transmission system to transmit the collected SERS spectral data to a computer in real time for signal processing and analysis. Therefore, the proposed Ag NPs@W-PDMS SERS substrate fabricated through a simple and mass-producible method, combined with the utilization of a portable Raman spectrometer and wireless communication, offers a promising opportunity to extend the SERS technique from the laboratory to POCT applications.

Molecular Mechanism of Mouse Uterine Smooth Muscle Regulation on Embryo Implantation.

Myometrium plays critical roles in multiple processes such as embryo spacing through peristalsis during mouse implantation, indicating vital roles of smooth muscle in the successful establishment and quality of implantation. Actin, a key element of cytoskeleton structure, plays an important role in the movement and contraction of smooth muscle cells (SMCs). However, the function of peri-implantation uterine smooth muscle and the regulation mechanism of muscle tension are still unclear. This study focused on the molecular mechanism of actin assembly regulation on implantation in smooth muscle. Phalloidin is a highly selective bicyclic peptide used for staining actin filaments (also known as F-actin). Phalloidin staining showed that F-actin gradually weakened in the CD-1 mouse myometrium from day 1 to day 4 of early pregnancy. More than 3 mice were studied for each group. Jasplakinolide (Jasp) used to inhibit F-actin depolymerization promotes F-actin polymerization in SMCs during implantation window and consequently compromises embryo implantation quality. Transcriptome analysis following Jasp treatment in mouse uterine SMCs reveals significant molecular changes associated with actin assembly. Tagln is involved in the regulation of the cell cytoskeleton and promotes the polymerization of G-actin to F-actin. Our results show that Tagln expression is gradually reduced in mouse uterine myometrium from day 1 to 4 of pregnancy. Furthermore, progesterone inhibits the expression of Tagln through the progesterone receptor. Using siRNA to knock down Tagln in day 3 SMCs, we found that phalloidin staining is decreased, which confirms the critical role of Tagln in F-actin polymerization. In conclusion, our data suggested that decreases in actin assembly in uterine smooth muscle during early pregnancy is critical to optimal embryo implantation. Tagln, a key molecule involved in actin assembly, regulates embryo implantation by controlling F-actin aggregation before implantation, suggesting moderate uterine contractility is conducive to embryo implantation. This study provides new insights into how the mouse uterus increases its flexibility to accommodate implanting embryos in the early stage of pregnancy.

Network of Tourism-Industrial Complex in Cities: Typologies and Implications through a Critical Literature Review.

Although tourism has increasingly become an important activity with wide influences on the economic, social, and spatial development of a city, knowledge and interest mostly remain on its industrial performance and promotion. The synergy between tourism and city development is largely overlooked in many cases, resulting in suboptimal design and planning of city tourism activities and unfledged potentials of city development. The aim of the paper is to propose a view of tourism-industrial complex based on a synergistic perspective in order to clarify the systematic characteristics of urban tourism in an integrated, sustainable manner. Availing of bibliometric methods and drawing on city/urban tourism literature, this paper proposes a concept of tourism-industrial complex to cover current complicated and various tourism activities that are embedded in cities at diverse levels regardless of social, economic, and spatial factors. Then, four types of tourism-industrial complexes are proposed, including demand-driven, resource-dependent, externally forced, and hybrid-driven models. Due to the networked connectivity of urban tourism, urban backgrounds, tourism industry, and external circumstances all contribute to a coupling the tourism city development system. The results provide theoretical constructs and policy recommendations for optimization and sustainable city and tourism development.

Caveolin-1 Regulation and Function in Mouse Uterus during Early Pregnancy and under Human In Vitro Decidualization.

Decidualization is essential to rodent and primate pregnancy. Senescence is increased during decidualization. Failure of senescence clearance during decidualization will cause pregnancy abnormality. Caveolin-1 is located in plasmalemmal caveolae and involved in senescence. However, whether caveolin-1 is involved in decidualization remains undefined. In this study, we examined the expression, regulation and function of Caveolin-1 during mouse early pregnancy and under mouse and human in vitro decidualization. From days 1 to 8 of pregnancy, Caveolin-1 signals are mainly located in endothelium and myometrium. Estrogen stimulates Caveolin-1 expression in endothelium. Deficiency of estrogen receptor α significantly promotes Caveolin-1 level in uterine stromal cells. Progesterone upregulates Caveolin-1 expression in luminal epithelium. During mouse in vitro decidualization, Caveolin-1 is significantly increased. However, Caveolin-1 is obviously decreased during human in vitro decidualization. Caveolin-1 overexpression and siRNA suppress and upregulate IGFBP1 expression under in vitro decidualization, respectively. Blastocysts-derived tumor necrosis factor α (TNFα) and human Chorionic Gonadotropin (hCG) regulate Caveolin-1 in mouse and human decidual cells, respectively. Caveolin-1 levels are also regulated by high glucose and insulin. In conclusion, a low level of Caveolin-1 should be beneficial for human decidualization.

Expression and Regulation of a Novel Decidual Cells-Derived Estrogen Target during Decidualization.

During decidualization in rodents, uterine stromal cells undergo extensive reprogramming to differentiate into distinct cell types, forming primary decidual zones (PDZs), secondary decidual zones (SDZs), and layers of undifferentiated stromal cells. The formation of secondary decidual zones is accompanied by extensive angiogenesis. During early pregnancy, besides ovarian estrogen, de novo synthesis of estrogen in the uterus is essential for the progress of decidualization. However, the molecular mechanisms are not fully understood. Studies have shown that Cystatin B (Cstb) is highly expressed in the decidual tissue of the uterus, but the regulation and mechanism of Cstb in the process of decidualization have not been reported. Our results showed that Cstb was highly expressed in mouse decidua and artificially induced deciduoma via in situ hybridization and immunofluorescence. Estrogen stimulates the expression of Cstb through the Estrogen receptor (ER)α. Moreover, in situ synthesis of estrogen in the uterus during decidualization regulates the expression of Cstb. Silencing the expression of Cstb affects the migration ability of stromal cells. Knockdown Cstb by siRNA significantly inhibits the expression of Dtprp, a marker for mouse decidualization. Our study identifies a novel estrogen target, Cstb, during decidualization and reveals that Cstb may play a pivotal role in angiogenesis during mouse decidualization via the Angptl7.

Female reproductive abnormalities in mouse adolescent pregnancy.

There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.

G protein-coupled estrogen receptor 1 inhibits the epithelial-mesenchymal transition of goat mammary epithelial cells via NF-κB signalling pathway.

Mastitis is one of the most frequent clinical diseases in dairy animals. Epithelial cells undergoing epithelial-mesenchymal transition (EMT) promote the process of mastitis. Oestrogen deficiency is disadvantaged of many tissue inflammation and regeneration, while exogenous oestrogen treatment can reverse these effects. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor. However, the potential effects of oestrogen via GPER1 on EMT in goat mammary epithelial cells (GMECs) are still unclear. Here, this study discovered that the activation of GPER1 by oestrogen could inhibit the EMT in GMECs via NF-κB signalling pathway. The activation of GPER1 by oestrogen inhibited the EMT accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Meanwhile, mRNA expression of transcription factors including Snail1 and ZEB1 was decreased. Further, like to oestrogen, GPER1 agonist G1 repressed the EMT progression. Conversely, GPER1 antagonist G15 reversed all these features induced by oestrogen. What's more, GPER1 silencing with shRNA promoted GMECs undergoing EMT. Additionally, oestrogen increased the phosphorylation of Erk1/2, which then decreased the phosphorylation and nuclear translocation of NF-κB, inhibiting the NF-κB signalling pathway activity. Taken, GPER1 may act as a suppressor through the regulation of EMT to prevent the development of mastitis.