H3K27me3 timely dictates uterine epithelial transcriptome remodeling and thus transformation essential for normal embryo implantation.

Uterine luminal epithelia (LE), the first layer contacting with the blastocyst, acquire receptivity for normal embryo implantation. Besides the well-accepted transcriptional regulation dominated by ovarian estrogen and progesterone for receptivity establishment, the involvement of epigenetic mechanisms remains elusive. This study systematically profiles the transcriptome and genome-wide H3K27me3 distribution in the LE throughout the preimplantation. Combining genetic and pharmacological approaches targeting the PRC2 core enzyme Ezh1/2, we demonstrate that the defective remodeling of H3K27me3 in the preimplantation stage disrupts the differentiation of LE, and derails uterine receptivity, resulting in implantation failure. Specifically, crucial epithelial genes, Pgr, Gata2, and Sgk1, are transcriptionally silenced through de novo deposition of H3K27me3 for LE transformation, and their sustained expression in the absence of H3K27me3 synergistically confines the nuclear translocation of FOXO1. Further functional studies identify several actin-associated genes, including Arpin, Tmod1, and Pdlim2, as novel direct targets of H3K27me3. Their aberrantly elevated expression impedes the morphological remodeling of LE, a hindrance alleviated by treatment with cytochalasin D which depolymerizes F-actin. Collectively, this study uncovers a previously unappreciated epigenetic regulatory mechanism for the transcriptional silencing of key LE genes via H3K27me3, essential for LE differentiation and thus embryo implantation.

Trophoblastic signals facilitate endometrial interferon response and lipid metabolism, ensuring normal decidualization.

The decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy.

Maternal Ezh1/2 deficiency impairs the function of mitochondria in mouse oocytes and early embryos.

Maternal histone methyltransferase is critical for epigenetic regulation and development of mammalian embryos by regulating histone and DNA modifications. Here, we reported a novel mechanism by revealing the critical effects of maternal Ezh1/2 deletion on mitochondria in MII oocytes and early embryos in mice. We found that Ezh1/2 knockout in mouse MII oocytes impaired the structure of mitochondria and decreased its number, but membrane potential and respiratory function of mitochondrion were increased. The similar effects of Ezh1/2 deletion have been observed in 2-cell and morula embryos, indicating that the effects of maternal Ezh1/2 deficiency on mitochondrion extend to early embryos. However, the loss of maternal Ezh1/2 resulted in a severe defect of morula: the number, membrane potential, respiratory function, and ATP production of mitochondrion dropped significantly. Content of reactive oxygen species was raised in both MII oocytes and early embryos, suggesting maternal Ezh1/2 knockout induced oxidative stress. In addition, maternal Ezh1/2 ablation interfered the autophagy in morula and blastocyst embryos. Finally, maternal Ezh1/2 deletion led to cell apoptosis in blastocyst embryos in mice. By analyzing the gene expression profile, we revealed that maternal Ezh1/2 knockout affected the expression of mitochondrial related genes in MII oocytes and early embryos. The chromatin immunoprecipitation-polymerase chain reaction assay demonstrated that Ezh1/2 directly regulated the expression of genes Fxyd6, Adpgk, Aurkb, Zfp521, Ehd3, Sgms2, Pygl, Slc1a1, and Chst12 by H3K27me3 modification. In conclusion, our study revealed the critical effect of maternal Ezh1/2 on the structure and function of mitochondria in oocytes and early embryos, and suggested a novel mechanism underlying maternal epigenetic regulation on early embryonic development through the modulation of mitochondrial status.

Effects of photoaging on structure and characteristics of biofilms on microplastic in soil: Biomass and microbial community.

Understanding of the environmental behaviors of microplastics is limited by a lack of knowledge about how photoaging influences biofilm formation on microplastics in soil. Here, original microplastics (OMPs) and photoaged-microplastics (AMPs) were incubated in soil to study the effect of photoaging on formation and characteristics of biofilm on the poly (butylene succinate) microplastics. Because photoaging decreased the hydrophobicity of the microplastic, the biomass of biofilm on the OMPs was nearly twice that on the AMPs in the early stage of incubation. However, the significance of the substrate on biomass in the biofilm declined as the plastisphere developed. The bacterial communities in the plastisphere were distinct from, and less diverse than, those in surrounding soil. The dominant genera in the OMPs and AMPs plastispheres were Achromobacter and Burkholderia, respectively, indicating that photoaging changed the composition of the bacterial community of biofilm at the genus level. Meantime, photoaging decreased the complexity and stability of the plastisphere bacterial community network. Results of Biolog ECO-microplate assays and functional prediction from amplicons showed that photoaging treatment enhanced the carbon metabolic capacity of the microplastic biofilm. This study provides new insights into the formation of plastispheres in soil.

Progesterone and cAMP synergistically induce SHP2 expression via PGR and CREB1 during uterine stromal decidualization.

Decidualization of endometrial stroma is a key step in embryo implantation and its abnormality often leads to pregnancy failure. Stromal decidualization is a very complex process that is co-regulated by estrogen, progesterone and many local factors. The signaling protein SHP2 encoded by PTPN11 is dynamically expressed in decidualized endometrial stroma and mediates and integrates various signals to govern the decidualization. In the present study, we investigate the mechanism of PTPN11 gene transcription. Estrogen, progesterone and cAMP co-induced decidualization of human endometrial stromal cell in vitro, but only progesterone and cAMP induced SHP2 expression. Using the luciferase reporter, we refined a region from -229 bp to +1 bp in the PTPN11 gene promoter comprising the transcriptional core regions that respond to progesterone and cAMP. Progesterone receptor (PGR) and cAMP-responsive element-binding protein 1 (CREB1) were predicted to be transcription factors in this core region by bioinformatic methods. The direct binding of PGR and CREB1 on the PTPN11 promoter was confirmed by electrophoretic mobility and chromatin immunoprecipitation in vitro. Knockdown of PGR and CREB1 protein significantly inhibited the expression of SHP2 induced by medroxyprogesterone acetate and cAMP. These results demonstrate that transcription factors PGR and CREB1 bind to the PTPN11 promoter to regulate the expression of SHP2 in response to decidual signals. Our results explain the transcriptional expression mechanism of SHP2 during decidualization and promote the understanding of the mechanism of decidualization of stromal cells.

The presence of blastocyst within the uteri facilitates lumenal epithelium transformation for implantation via upregulating lysosome proteostasis activity.

ABBREVIATIONS: ACTB: actin beta; AREG: amphiregulin; ATP6V0A4: ATPase, H+ transporting, lysosomal V0 subunit A4; Baf A1: bafilomycin A1; BSA: bovine serum albumin; CLDN1: claudin 1; CTSB: cathepsin B; DEGs: differentially expressed genes; E2: 17ß-estradiol; ESR: estrogen receptor; GATA2: GATA binding protein 2; GLA: galactosidase, alpha; GO: gene ontology; HBEGF: heparin-binding EGF-like growth factor; IGF1R: insulin-like growth factor 1 receptor; Ihh: Indian hedgehog; ISH: in situ hybridization; LAMP1: lysosomal-associated membrane protein 1; LCM: laser capture microdissection; Le: lumenal epithelium; LGMN: legumain; LIF: leukemia inhibitory factor; LIFR: LIF receptor alpha; MSX1: msh homeobox 1; MUC1: mucin 1, transmembrane; P4: progesterone; PBS: phosphate-buffered saline; PCA: principal component analysis; PPT1: palmitoyl-protein thioesterase 1; PGR: progesterone receptor; PSP: pseudopregnancy; PTGS2/COX2: prostaglandin-endoperoxide synthase 2; qPCR: quantitative real-time polymerase chain reaction; SP: pregnancy; TFEB: transcription factor EB.

Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution.

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth.

Effect of carbon nanomaterials on functional diversity and structure of soil microbial community under single and repeated exposures.

The extensive application of carbon nanomaterials (CNMs) has attracted increasing studies concerned about its environmental impact. These studies focus on single exposure to CNMs, but repeated exposures with relatively low concentration are more likely to occur under actual exposure scenario. In this study, we studied the metabolic functional and structure of soil microorganism community under single and repeated exposures to multiwalled carbon nanotubes (MW), graphene (GR), and fullerene (C60) by Biolog EcoPlates and high-throughput sequencing. Our findings revealed that repeated exposures to CNMs significantly increase the metabolic activity and diversity of the soil microbial community as compared with single exposure. Principal component and similarity analysis not only indicated that GR exerted a stronger effect on soil microbial diversity among three exposures compared to C60 and MW, but also revealed that the metabolic activity of the soil microbial community was more affected by the exposure scenarios of CNMs than the type of CNMs. These findings elucidated the effect of CNMs under different exposure scenarios on soil microorganism community, providing a new perspective on the risk assessment of nanomaterials.

Stromal cells-specific retinoic acid determines parturition timing at single-cell and spatial-temporal resolution.

The underlying mechanisms governing parturition remain largely elusive due to limited knowledge of parturition preparation and initiation. Accumulated evidences indicate that maternal decidua plays a critical role in parturition initiation. To comprehensively decrypt the cell heterogeneity in decidua approaching parturition, we investigate the roles of various cell types in mouse decidua process and reveal previously unappreciated insights in parturition initiation utilizing single-cell RNA sequencing (scRNA-seq). We enumerate the cell types in decidua and identity five different stromal cells populations and one decidualized stromal cells. Furthermore, our study unravels that stromal cells prepare for parturition by regulating local retinol acid (RA) synthesis. RA supplement decreases expression of extracellular matrix-related genes in vitro and accelerates the timing of parturition in vivo. Collectively, the discovery of contribution of stromal cells in parturition expands current knowledge about parturition and opens up avenues for the intervention of preterm birth (PTB).

Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation.

BACKGROUND: Traditional Chinese medicine has been used for a long time to treat a variety of gynecological diseases. Among various traditional Chinese medicine, Dingkun Pill (DK) has been used for the treatment of female gynecological diseases. However, DK therapeutic effect on PCOS and the target tissue for its potential effect need to be explored. This study aims to explore the therapeutic effect of DK for PCOS in mice from three aspects: metabolism, endocrine and fertility, and determine whether the brown adipose tissue is the target organ to alleviate the PCOS phenotype. METHODS: PCOS mouse model was constructed by subcutaneous injection of DHEA. The estrous cycle, ovulation, and pregnancy outcome was examined in mice. The level of hormone including the LH, FSH, estrogen and testosterone in the serum were measured by ELISA. Both the glucose sensitivity and insulin sensitivity were determined in mice with different treatment. The histomorphology and lipid contents in the brown adipose tissue were analyzed. RNA-Seq was conducted for the brown adipose tissue and different expression of critical metabolism marker genes was confirmed by real-time PCR. RESULTS: The data showed that the fertility in PCOS mice with DK treatment was significantly increased, and the metabolic disorder was partially restored. Both the whiten of brown adipose tissue and reduced UCP1 expression induced by DHEA was rescued by the DK. The RNA-Seq data further demonstrated both the DHEA induced downregulation of lipolysis genes and oxidative phosphorylation genes were at least partially rescued by DK in the brown adipose tissue. CONCLUSIONS: DK has therapeutic effect on PCOS in DHEA treated mice and the brown adipose tissue is at least one critical target organ to alleviate the PCOS. This is achieved by not only regulating the lipid mobilization of brown adipose, but also restoring its thermogenic function.

Gαq-PKD/PKCµ signal regulating the nuclear export of HDAC5 to induce the IκB expression and limit the NF-κB-mediated inflammatory response essential for early pregnancy.

Decidualization, denoting the transformation of endometrial stromal cells into specialized decidual cells, is a prerequisite for normal embryo implantation and a successful pregnancy in human. Here, we demonstrated that knockout of Gαq lead to an aberrantly enhanced inflammatory state during decidualization. Furthermore, we showed that deficiency of Gαq resulted in over-activation of nuclear factor (NF)-κB signaling, due to the decreased expression of NFκBIA, which encode the IκB protein and is the negative regulator for NF-κB. Mechanistically, Gαq deficiency decreased the Protein kinase D (PKD, also called PKCµ) phosphorylation levels, leading to attenuated HDAC5 phosphorylation and thus its nuclear export. Aberrantly high level of nuclear HDAC5 retarded histone acetylation to inhibit the induced NFκBIA transcription during decidualization. Consistently, pharmacological activation of the PKD/PKCµ or inhibition of the HDAC5 restored the inflammatory state and proper decidual response. Finally, we disclosed that over-active inflammatory state in Gαq-deficient decidua deferred the blastocyst hatching and adhesion in vitro, and the decidual expression of Gαq was significantly lower in women with recurrent pregnancy loss compared with normal pregnancy. In brief, we showed here that Gαq as a key regulator of the inflammatory cytokine's expression and decidual homeostasis in response to differentiation cues, which is required for successful implantation and early pregnancy.

Trophoblast PR-SET7 dysfunction induces viral mimicry response and necroptosis associated with recurrent miscarriage.

Recurrent miscarriage (RM) is a distressing pregnancy complication. While the etiology of RM remains unclear, growing evidence has indicated the relevance of trophoblast impairment to the pathogenesis of RM. PR-SET7 is the sole enzyme catalyzing monomethylation of H4K20 (H4K20me1) and has been implicated in many pathophysiological processes. However, how PR-SET7 functions in trophoblasts and its relevance to RM remain unknown. Here, we found that trophoblast-specific loss of Pr-set7 in mice led to defective trophoblasts, resulting in early embryonic loss. Mechanistic analysis revealed that PR-SET7 deficiency in trophoblasts derepressed endogenous retroviruses (ERVs), leading to double-stranded RNA stress and subsequent viral mimicry, which drove overwhelming interferon response and necroptosis. Further examination discovered that H4K20me1 and H4K20me3 mediated the inhibition of cell-intrinsic expression of ERVs. Importantly, dysregulation of PR-SET7 expression and the corresponding aberrant epigenetic modifications were observed in the placentas of RM. Collectively, our results demonstrate that PR-SET7 acts as an epigenetic transcriptional modulator essential for repressing ERVs in trophoblasts, ensuring normal pregnancy and fetal survival, which sheds new light on potential epigenetic causes contributing to RM.

Tissue-Specific RNA Localization in the Uterus During Implantation, Decidualization and Placentation: Technical Nuances of Various Labeling Approaches.

In situ hybridization (ISH) is a sensitive method used to localize a specific sequence of DNA or RNA in biological samples, including cells, tissue sections or whole organs. RNA ISH can be used to determine spatial gene expression using a single-stranded probe with a reverse-complementary sequence. Cell-specific gene expression has been studied using mRNA and protein levels. Signals produced by RNA probes are usually more specific than those produced by antibodies in immunostaining. Currently, ISH is the most widely used method to localize mRNA molecules. Traditionally, probes were labeled with radioactive isotopes, but the cumbersome procedures and potential health risk limit their acceptance. Recently, probes labeled with nonradioactive materials including digoxigenin, biotin and various fluorophores have been developed. The tyramide signal amplification system further enhances the sensitivity of detection. These methods have been applied in numerous studies in various tissues including reproductive organs. This article details three methods of RNA in situ hybridization: radioactive in situ hybridization, digoxigenin in situ hybridization, and digoxigenin-tyramide signal amplification fluorescein in situ hybridization. The pros and cons of each protocol are discussed. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Radioactive in situ hybridization (radioactive-ISH) Basic Protocol 2: Digoxigenin in situ hybridization (DIG-ISH) Basic Protocol 3: Digoxigenin-tyramide signal amplification fluorescein in situ hybridization (DIG-TSA-FISH).

JAZF1 safeguards human endometrial stromal cells survival and decidualization by repressing the transcription of G0S2.

Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purß. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purß, and highlight the clinical implications of these mechanisms in the pathology of RSA.

Effects of incorporating Mn into goethite on adsorption of dissolved organic matter and potentially toxic elements in soil: Isotherms, kinetics, and mechanisms.

Goethite is ubiquitous in the environment and plays key role in preserving dissolved organic matter (DOM) and deactivating potentially toxic elements (PTEs) by adsorbing DOM and PTEs. Various non-Fe metals are usually incorporated into natural goethite, substituting Fe in the goethite structure, which dramatically influence the physico-chemical properties and adsorption behavior of the goethite. In the present study, adsorption of DOM and Pb(II) on Mn-substituted goethite samples was investigated. The results displayed that the specific surface area (SSA) of mineral samples increased by 67.6% as the incorporation of Mn for Fe, from 25.71 m2 g-1 for pure goethite to 43.09 m2 g-1for Mn-goethite. Besides, the Mn substitution caused more hydroxyl groups and relatively fewer positive charges on mineral surface, and Mn in the Mn-goethite samples was predominantly present as Mn(III). The amount of DOM adsorbed to per unit mass of goethite was increased as Mn content increased, which was attributed to Mn incorporation increasing the SSA of mineral samples. However, the SSA-normalized absorption capacity for goethite to DOM was decreased by Mn because Mn substitution decreased the number of positive charges of mineral samples, which weakened the electrostatic attraction between DOM and the minerals. The amount of Pb(II) adsorbed to per unit mass of goethite was increased by Mn substitution, and the amount of Pb(II) adsorbed to per unit SSA of goethite increased as the amount of Mn substitution increased, indicating that the increased capacity for adsorbing Pb was not only caused by the SSA increasing but also by there were more surface hydroxyl groups on the Mn-goethite than pure goethite and Pb(II) preferentially adsorbed to Mn sites on the Mn-goethite. The present study results showed that Mn-goethite could be used to sequester DOM and remediate soil contaminated with PTEs because Mn-goethite has a high adsorption capacity and is environmentally benign.

Endogenous retrovirus-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization.

Endogenous retroviruses (ERVs) have been proposed as a driving force for the evolution of the mammalian placenta, however, the contribution of ERVs to placental development and the underlying regulatory mechanism remain largely elusive. A key process of placental development is the formation of multinucleated syncytiotrophoblasts (STBs) in direct contact with maternal blood, through which constitutes the maternal-fetal interface critical for nutrient allocation, hormone production and immunological modulation during pregnancy. We delineate that ERVs profoundly rewire the transcriptional program of trophoblast syncytialization. Here, we first determined the dynamic landscape of bivalent ERV-derived enhancers with dual occupancy of H3K27ac and H3K9me3 in human trophoblast stem cells (hTSCs). We further demonstrated that enhancers overlapping several ERV families tend to exhibit increased H3K27ac and reduced H3K9me3 occupancy in STBs relative to hTSCs. Particularly, bivalent enhancers derived from the Simiiformes-specific MER50 transposons were linked to a cluster of genes important for STB formation. Importantly, deletions of MER50 elements adjacent to several STB genes, including MFSD2A and TNFAIP2, significantly attenuated their expression concomitant to compromised syncytium formation. Together, we propose that ERV-derived enhancers, MER50 specifically, fine-tune the transcriptional networks accounting for human trophoblast syncytialization, which sheds light on a novel ERV-mediated regulatory mechanism underlying placental development.

Identification of factors controlling heavy metals/metalloid distribution in agricultural soils using multi-source data.

Understanding the factors that controlling the agricultural soil heavy metals/metalloids distribution is vital for cropland soil remediation and management. For this objective, 227 agricultural soils were sampled in the Guanzhong Plain, China, to measure the concentration of five heavy metals (Pb, Cd, Ni, Zn, and Cu) and one metalloid (As) by X-ray fluorescence spectrometer, meanwhile, 24 possible influencing factors to agricultural soil heavy metals/metalloid distribution were collected and grouped into three categories. A sequential multivariate statistical analysis was carried out to provide insight into the controlling factors of soil heavy metals/metalloid distribution, then stepwise multiple linear regression (SMLR) and partial least squares regression (PLS) were used to predict heavy metals/metalloid concentrations in agricultural soil based on the result of soil heavy metals/metalloid controlling factors identification. The results demonstrated the types of soil and land use did not have a substantial effect on soil heavy metals/metalloid distribution, except Zn and Cu. The soil properties category played a major role in influencing the soil heavy metals/metalloid concentration. The concentrations of Mn and Fe, which are the main constitute elements of soil inorganic colloid, were the most significant factors, followed by the concentrations of P, K and Ca. Soil pH and soil organic matter (SOM) content, which are often considered as important factors for soil heavy metals/metalloid distribution, were not important in the present study. The SMLR was more effective than the PLS for predicting soil heavy metals/metalloid content. The results of this study enlighten that future soil heavy metals/metalloid contamination treatment in regions with high pH and low SOM content should concentrate on inorganic colloid particles, which have strong adsorption capacity for soil heavy metals/metalloid and are environmentally friendly. Moreover, the combination of successive multivariate statistical analysis and SMLR provide an effective tool to predict and monitor agricultural soil heavy metals/metalloid distribution, and facilitate the improvement of environmental and territorial management.

[Analysis of Critical Source of Potentially Harmful Elements in Urban Road Dust During Winter in Taiyuan Based on Multiple Attribute Decision Making Method].

In order to analyze the critical sources of potential harmful elements (PHEs) in road dust from Taiyuan during winter, 40 road dust samples were collected. The contents of PHEs, including As, Cd, Pb, Ni, Cr, Cu, and Zn, in the road dust samples were measured using inductively coupled plasma mass spectrometry and atomic fluorescence spectrometry. The ecological risks and human health risks posed by dust PHEs were assessed using NIRI and a health risk evaluation model recommended by USEPA, respectively. The sources of dust PHEs were identified by using the combination of principal component analysis and positive matrix factorization (PMF); the total PHE contents and the ecological risks and human health risks posed by PHEs in dust were apportioned to the PHE sources based on the PMF results; subsequently, the critical source of dust PHEs was determined using the multiple attribute decision making method (MADM). The results demonstrated that: 1 the average concentrations of As, Cd, Pb, Ni, Cr, Cu, and Zn were 17.92, 0.32, 69.10, 30.06, 107.74, 73.37, and 268.49 mg·kg-1, respectively, which were higher than the corresponding background values of soil in Taiyuan, indicating that the PHEs had accumulated in road dust; the mean value of NIRI was 63.86, demonstrating that PHEs in dust posed moderate risks, and the dust PHEs pollution was controllable. 2 Human health risk assessment indicated that exposure to PHEs in dust did not pose serious non-carcinogenic or carcinogenic risks. Ingestion was the most important pathway for exposure to PHEs in road dust that damages human health, and As and Cr have been found to pose the most risks among the seven PHEs. 3 The present study found three main sources of PHEs measured in the dust: natural, traffic, and industrial, which accounted for 35.95%, 40.25%, and 23.82% of the total concentrations of PHEs, respectively. 4 Industrial emissions contributed the least to the total PHEs contents in dust; however, the PHEs released from industrial sources caused relatively high risks, with the results of MADM indicating that industrial sources were the most critical source for dust PHEs. Our results indicated that the critical source identification of PHEs, which was determined to be the most pernicious source, could provide reference for subsequent pollution source control.

Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.

BACKGROUND: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial ß3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. METHODS: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. FINDINGS: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast-uterine epithelium adhesion. The effect of Nur77 mediated trophoblast-uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target ß3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2-4)] vs [3 (2-4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. INTERPRETATION: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/ß3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. FUNDING: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869).

Eutrophication induces functional homogenization and traits filtering in Chinese lacustrine fish communities.

Rapid anthropogenic nutrient enrichment has caused widespread ecological problems in aquatic ecosystems and the resulting eutrophication has dramatically changed fish communities throughout the world. However, few studies addressed how fish communities responded to eutrophication in terms of multidimensional functional and taxonomic structure, especially how eutrophication acted as an environment filter on functional traits. The aim of the present study was to investigate the effects of eutrophication on fish species composition, community metrics and species functional traits in 26 shallow lakes from the middle reaches of Yangtze River basin, China. This study validated that eutrophication is an important factor shaping the fish community structure. Regression analyses showed that eutrophication favored higher total biomass and lower functional diversity of fish communities but had little effect on species richness. Despite the fact that some pelagic zooplanktivorous species were more abundant in the most eutrophic lakes, multivariate analyses of the relationships between species traits and environmental variables revealed weak relationships between feeding traits and eutrophication. In contrast, species with a benthic life stage were negatively associated with eutrophication while those with a large body size and high absolute fecundity showed the opposite trend. Due to demersal habitat degradation, and to a lesser degree, to changes in trophic resources availability, eutrophication caused functional simplification of fish communities by increasing functional traits homogeneity among the most tolerant species. Some relationships between functional traits and eutrophication well established in the western palearctic have not been observed in this study, emphasizing the importance of biases resulting from specific evolutionary histories. This work will provide useful insights on on-going restoration and management of shallow lakes in the Yangtze River basin.