Decreased NSD2 impairs stromal cell proliferation in human endometrium via reprogramming H3K36me2.

In brief: The proliferation of the endometrium is regulated by histone methylation. This study shows that decreased NSD2 impairs proliferative-phase endometrial stromal cell proliferation in patients with recurrent implantation failure via epigenetic reprogramming of H3K36me2 methylation on the promoter region of MCM7. Abstract: Recurrent implantation failure (RIF) is a formidable challenge in assisted reproductive technology because of its unclear molecular mechanism. Impaired human endometrial stromal cell (HESC) proliferation disrupts the rhythm of the menstrual cycle, resulting in devastating disorders between the embryo and the endometrium. The molecular function of histone methylation enzymes in modulating HESC proliferation remains largely uncharacterized. Herein, we found that the levels of histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) and the dimethylation of lysine 36 on histone H3 are decreased significantly in the proliferative-phase endometrium of patients with RIF. Knockdown of NSD2 in an HESC cell line markedly impaired cell proliferation and globally reduced H3K36me2 binding to chromatin, leading to altered expression of many genes. Transcriptomic analyses revealed that cell cycle-related gene sets were downregulated in the endometrium of patients with RIF and in NSD2­knockdown HESCs. Furthermore, RNA-sequencing and CUT&Tag sequencing analysis suggested that NSD2 knockdown reduced the binding of H3K36me2 to the promoter region of cell cycle marker gene MCM7 (encoding minichromosome maintenance complex component 7) and downregulated its expression. The interaction of H3K36me2 with the MCM7 promoter was verified using chromatin immunoprecipitation-quantitative real-time PCR. Our results demonstrated a unifying epigenome-scale mechanism by which decreased NSD2 impairs endometrial stromal cell proliferation in the proliferative-phase endometrium of patients with RIF.

Arbitrary fabrication of complex lithium niobate three-dimensional microstructures for second harmonic generation enhancement.

Lithium niobate (LN) crystal plays important roles in future integrated photonics, but it is still a great challenge to efficiently fabricate three-dimensional micro-/nanostructures on it. Here, a femtosecond laser direct writing-assisted liquid back-etching technology (FsLDW-LBE) is proposed to achieve the three-dimensional (3D) microfabrication of lithium niobate (LN) with high surface quality (Ra = 0.422 nm). Various 3D structures, such as snowflakes, graphic arrays, criss-cross arrays, and helix arrays, have been successfully fabricated on the surface of LN crystals. As an example, a microcone array was fabricated on LN crystals, which showed a strong second harmonic signal enhancement with up to 12 times bigger than the flat lithium niobate. The results indicate that the method provides a new approach for the microfabrication of lithium niobate crystals for nonlinear optics.

Complete composition analysis of polysaccharides based on HPAEC-PAD coupled with quantitative analysis of multi-components by single marker.

INTRODUCTION: Monosaccharide compositions analysis (MCA) is indispensable for structural characterisations and structure-activity relationships of plant polysaccharides. OBJECTIVES: To develop a concise and direct MCA method, we established a quantitative analysis of the multi-monosaccharaides by single marker (QAMS) by high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD) method. METHODOLOGY: A stable and reproducible HPAEC-PAD method for simultaneous determination of aldoses, ketoses and uronic acids (i.e., l-arabinose, d-xylose, d-ribose, l-rhamnose, d-fucose, d-mannose, d-glucose, d-galactose, d-fructose, d-glucuronic acid and d-galacturonic acid) was established by systematic optimisation of stationary phases, column temperatures and elution programmes. On this basis, the QAMS method was proposed through comprehensive investigations of relative correction factor (RCF) variations under different influencing factors, for example, sample concentrations, flow rates, and column temperatures. RESULTS: Using rhamnose as an internal reference standard, the contents of the other monosaccharide components in polysaccharides from Panax quinquefolium L. and Achyranthes bidentata Bl. samples were simultaneously determined by QAMS, and there was no significant difference between the results from the QAMS and external standard method (t test, P > 0.520). In addition, a MCA fingerprinting of 30 batches of P. quinquefolium polysaccharide was established by HPAEC-PAD, and six common peaks were assigned and determined. CONCLUSIONS: The established HPAEC-PAD-QAMS method was successfully applied to the MCA of polysaccharides from P. quinquefolium and A. bidentata after optimisation of hydrolysis conditions. HPAEC-PAD-QAMS was proposed and established for MCA of plant polysaccharides for the first time.

Integration of cross-scale milli/microlenses by ion beam etching and femtosecond laser modification.

Integrated cross-scale milli/microlenses offer irreplaceable functions in modern integrated optics with the advantage of reducing the size of the optical system to millimeters or microns. However, the technologies for fabricating millimeter-scale lenses and microlenses are always incompatible, which makes the successful fabrication of cross-scale milli/microlenses with a controlled morphology challenging. Here, ion beam etching is proposed as a means to fabricate smooth millimeter-scale lenses on various hard materials. In addition, by combining femtosecond laser modification and ion beam etching, an integrated cross-scale concave milli/microlens (27,000 microlenses on a lens with a diameter of 2.5 mm) is demonstrated on fused silica, and can be used as the template for a compound eye. The results provide a new, to the best of our knowledge, route for the flexible fabrication of cross-scale optical components for modern integrated optical systems.

Wafer-scale high aspect-ratio sapphire periodic nanostructures fabricated by self-modulated femtosecond laser hybrid technology.

Sapphire nanostructures with a high aspect-ratio have broad applications in photoelectronic devices, which are difficult to be fabricated due to the properties of high transparency and hardness, remarkable thermal and chemical stability. Although the phenomenon of laser-induced periodic surface structures (LIPSS) provides an extraordinary idea for surface nanotexturing, it suffers from the limitation of the small depth of the nanostructures. Here, a high-efficiency self-modulated femtosecond laser hybrid technology was proposed to fabricate nanostructures with high aspect-ratios on the sapphire surface, which was combined backside laser modification and subsequent wet etching. Due to the refractive index mismatch, the focal length of the laser could be elongated when focused inside sapphire. Thus, periodic nanostructures with high-quality aspect ratios of more than 55 were prepared on the sapphire surface by using this hybrid fabrication method. As a proof-of-concept, wafer-scale (∼2 inches) periodic nanostripes with a high aspect-ratio were realized on a sapphire surface, which possesses unique diffractive properties compared to typical shallow gratings. The results indicate that the self-modulated femtosecond laser hybrid technology is an efficient and versatile technique for producing high aspect-ratio nanostructures on hard and transparent materials, which would propel the potential applications in optics and surface engineering, sensing, etc.

TCF3 regulates human endometrial stromal cell proliferation and migration in RPL.

Recurrent pregnancy loss (RPL) is a multifactorial condition with no explanation of miscarriage in approximately half of the RPL patients, consequently leaving deep physical and emotional sequels. Transcription factor 3 (TCF3 or E2A), is a unique member of the LEF/TCF family and plays an important role in embryogenesis. However, its function in RPL is poorly understood. Using real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry, we demonstrated that TCF3 was downregulated in decidual tissues from RPL patients compared with healthy control (HC). Further, TCF3 knockdown inhibited proliferation, induced G0/G1 phase arrest, and promoted migration in human endometrial stromal cells (HESCs), while overexpression of TCF3 exhibited the opposite effects. RNA-sequencing analysis combined with gene-set enrichment analysis results showed that the mitogen-activated protein kinase pathway is potentially downstream of TCF3. Knockdown of TCF3 confirmed increased p38 phosphorylation, while overexpression of TCF3 inhibited p38 phosphorylation. Furthermore, we found that TCF3 protein level was decreased in HESCs under hypoxic incubation, while hypoxia-inducible factor-1α (HIF1A) knockdown increased the expression of TCF3. TCF3 overexpression recovered the proliferation ability of HESCs inhibited by hypoxia and reversed hypoxia-induced migration. Consistently, we found that RPL patients had a significantly higher level of HIF1A in the decidual tissue than HC. Overall, this study clarifies that increased HIF1A in the decidua contributes to the occurrence of RPL through the TCF3/p38 signaling pathway.

Acbp is essential for decidualization during early pregnancy in mice.

Decidualization of uterine stromal cells plays an important role in the establishment of normal pregnancy. Previous studies have demonstrated that Acyl-CoA binding protein (Acbp) is critical to cellular proliferation, differentiation, mitochondrial functions, and autophagy. The characterization and physiological function of Acbp during decidualization remain largely unknown. In the present study, we conducted the expression profile of Acbp in the endometrium of early pregnant mice. With the occurrence of decidualization, the expression of Acbp gradually increased. Similarly, Acbp expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. We applied the mice pseudopregnancy model to reveal that the expression of Acbp in the endometrium of early pregnant mice was not induced by embryonic signaling. Moreover, P4 significantly upregulated the expression of Acbp, whereas E2 appeared to have no regulating effect on Acbp expression in uterine stromal cells. Concurrently, we found that interfering with Acbp attenuated decidualization, and that might due to mitochondrial dysfunctions and the inhibition of fatty acid oxidation. The level of autophagy was increased after knocking down Acbp. During induced decidualization, the expression of ACBP was decreased with the treatment of rapamycin (an autophagy inducer), while increased with the addition of Chloroquine (an autophagy inhibitor). Our work suggests that Acbp plays an essential role in the proliferation and differentiation of stromal cells during decidualization through regulating mitochondrial functions, fatty acid oxidation, and autophagy.

High-quality rapid laser drilling of transparent hard materials.

In this study, a hybrid method for high-quality rapid drilling of transparent hard materials which combines femtosecond laser (fs-laser) Bessel beam modifying materials and selective wet etching is presented. Using this method, micro-holes with no taper of different sizes (from 10 to 35 µm) and shapes (square, triangle, circular, and pentagram) are fabricated. Bessel beams of different lengths can be generated flexibly by loading different computer-generated holograms (CGHs) into the spatial light modulator (SLM) and the maximum length of light interacting with materials can reach 320 µm, leading to a reduction of the laser scanning time by two orders of magnitude. Moreover, a set of three-dimensional multi-layer submicron through-holes in crystal materials is also realized, with an aspect ratio of more than 1000 for each hole. These results indicate that this method has broad application potential in chip packaging, aviation manufacturing, single particle catalysis, and other fields.

Smart Diffraction Gratings Based on the Shape Memory Effect.

The shape memory effect is the capability of a structure or a material that can be deformed into a certain temporary shape under external stimulus, and the shape will be fixed without the stimulus. The recovery process can be triggered by the same stimulus. The intelligent tunable device based on the shape memory effect has a wide range of applications in many fields. In the optical field, smart diffraction gratings can accomplish in situ optical diffractions according to requirements, meeting the high demand in the next generation of smart optical systems. However, it is essential to construct high-precision grating structures based on shape memory materials. Here, a smart diffraction grating based on UV-curable shape memory polymers (SMPs) via two-beam interference is reported, with nano-scale precision, excellent deformability and recovery ability, and adjustable spectroscopic performance. More importantly, based on the shape memory effect, grating structures that surpass the precision of the fabrication system can be obtained. The smart grating exhibits rapid deformation and recovery upon heating and long-term storage capability, which facilitates them to be applied in optics, electronics, and integrated sensing.

Clinical characteristics and related risk factors of disease severity in 101 COVID-19 patients hospitalized in Wuhan, China.

Coronavirus disease 2019 (COVID-19) broke out in December 2019. Due its high morbility and mortality, it is necessary to summarize the clinical characteristics of COVID-19 patients to provide more theoretical basis for future treatment. In the current study, we conducted a retrospective analysis of the clinical characteristics of COVID-19 patients and explored the risk factors for the severity of illness. A total of 101 COVID-19 patients hospitalized in Leishenshan Hospital (Wuhan, China) was classified into three sub-types: moderate (n = 47), severe (n = 36), and critical (n = 18); their clinical data were collected from the Electronic Medical Record. We showed that among the 101 COVID-19 patients, the median age was 62 years (IQR 51-74); 50 (49.5%) patients were accompanied by hypertension, while 25 (24.8%) and 22 (21.8%) patients suffered from diabetes and heart diseases, respectively, with complications. All patients were from Wuhan who had a definite history of exposure to the epidemic area. Multivariate logistic regression analysis revealed that older age, diabetes, chronic liver disease, percentage of neutrophils (N%) > 75%, CRP > 4 mg/L, D-dimer > 0.55 mg/L, IL-2R > 710 U/mL, IL-8 > 62 pg/mL, and IL-10 > 9.1 pg/mL were independent variables associated with severe COVID-19. In conclusion, we have identified the independent risk factors for the severity of COVID-19 pneumonia, including older age, diabetes, chronic liver disease, higher levels of N%, CRP, D-dimer, IL-2R, IL-8, and IL-10, providing evidence for more accurate risk prediction.

CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia.

Preeclampsia is a gestational hypertensive disease; however, preeclampsia remains poorly understood. Bioinformatics analysis was applied to find novel genes involved in the pathogenesis of preeclampsia and identified CLDN1 as one of the most differentially expressed genes when comparing patients with preeclampsia and healthy controls. The results of the qRT-PCR, Western blotting and immunohistochemistry experiments demonstrated that CLDN1 was significantly downregulated in the chorionic villi in samples from patients with preeclampsia. Furthermore, knockdown of CLDN1 in HTR-8/SVneo cells resulted in the inhibition of proliferation and induction of apoptosis, and overexpression of CLDN1 reversed these effects. In addition, RNA-seq assays demonstrated that the gene BIRC3 is potentially downstream of CLDN1 and is involved in the regulation of apoptosis. Knockdown of CLDN1 confirmed that the expression level of BIRC3 was obviously decreased and was associated with a significant increase in cleaved PARP. Interestingly, the apoptotic effect in CLDN1 knockdown cells was rescued after BIRC3 overexpression. Overall, these results indicate that a decrease in CLDN1 inhibits BIRC3 expression and increases cleaved PARP levels thus participating in the pathogenesis of preeclampsia.

Vector scanning subtractive manufacturing technology for laser rapid fabrication.

Herein, a vector scanning subtractive manufacturing technology is proposed to rapidly fabricate smooth micro-optical components, which is based on the vector scanning method and wet etching. Compared with the raster scanning method, the vector scanning method increases processing efficiency by nearly two orders and mitigates a buildup of stress around the laser processed region, avoiding the generation of cracks. The Letter demonstrates the fabrication of three-dimensional (3D) micro-structures with various sizes and morphologies. For example, micro-concave lenses with diameters of 20 µm to 140 µm, heights of 10 µm to 70 µm, and surface roughness of 29 nm are flexibly fabricated on sapphire by vector scanning subtractive manufacturing technology. The results indicate that the technology has broad prospects in the field of monolithic integrated 3D all-solid-state micro-optics.

FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy.

Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis-related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1-7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5-7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a-small interfering RNA was transfected into the uteri of mice, the expression of decidualization- and apoptosis-related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a-regulated decidualization.

Ultra-smooth micro-optical components of various geometries.

A dry-etching-assisted femtosecond laser lithography technology is proposed to in-site fabricate micro-optical components with an ultra-smooth three-dimensional continuous profile on a non-planar substrate. Owing to the nanometric resolution of femtosecond laser multi-photon polymerization and dry etching, smooth micro-optical components can be realized on hard materials with surface roughness of approximately 1.5 nm. With flexible and arbitrary designability of femtosecond laser lithography, various high-quality micro-optical components are realized on sapphire. These results indicate that dry-etching-assisted femtosecond laser lithography has promising potential for versatile fabrication of arbitrary ultra-smooth micro/nanostructures on hard materials.

Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats.

Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence suggests that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidence is scarce and the underlying mechanisms remain to be elucidated. We have recently demonstrated that bile acids induce activation of alveolar epithelial cells (AECs) and lung fibroblasts in vitro In the present study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA). Repeated microaspiration of CDCA, DCA, and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial-mesenchymal transition (EMT), as indicated by up-regulation of mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, as well as down-regulaton of epithelial markers E-cadherin and cytokeratin in alveolar epithelium of rat lungs. The expression of fibrogenic mediators, including transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and periostin, was significantly elevated in rat lungs exposed to microaspiration of bile acids. Furthermore, microaspiration of bile acids also induced p-Smad3 and farnesoid X receptor (FXR) expression in rat lungs. Our findings suggest that microaspiration of bile acids could promote the development of pulmonary fibrosis in vivo, possibly via stimulating fibrogenic mediator expression and activating TGF-ß1/Smad3 signaling and FXR.

Stomatin-like protein 2 is involved in endometrial stromal cell proliferation and differentiation during decidualization in mice and humans.

The molecular mechanisms underlying endometrial stromal cell proliferation and differentiation (decidualization) are still not fully understood. This study revealed that increased Slp-2 expression is a significant factor modulating endometrial stromal cell proliferation and decidualization in both mice and humans. Our results showed a significant difference in the mRNA and protein levels between the implantation site and inter-implantation site on day 5 and day 6 of pregnancy in mice (all P < 0.05). Strong Slp-2 immunostaining was mainly localized within the decidual zone of mice through the post-implantation period. Mice with artificially induced deciduoma showed significantly higher expression of Slp-2 compared with uninduced controls (P < 0.005). Human stromal cells in the middle and late-secretory phases demonstrated significantly (all P < 0.05) upregulated SLP-2, compared with cells in the proliferative phase and early secretory phases. Further analyses of the SLP-2 gene knocked down revealed a significant (P < 0.005) repression of both the decidualization marker gene's expression (decidual/trophoblast prolactin-related protein in mice, insulin-like growth factor binding protein and prolactin in human) and the cell proliferation in in vitro-induced decidualized primary endometrial stromal cells in mice and humans.

Methylated oligonucleotide (MON)-induced promoter hypermethylation is associated with repression of CDH1 expression and contributes to the migration and invasion of human trophoblast cell lines.

DNA cytosine-5 methylation plays a vital role in regulating the expression of E-cadherin, which is encoded by the CDH1 gene. In this study, we characterised the DNA methylation and expression pattern of CDH1 in an extravillous trophoblast cell line (HTR-8/SVneo) and two trophoblast cell lines -- JEG-3 and JAR. Promoter hypermethylation with reduced E-cadherin expression in HTR-8/SVneo cells and promoter hypomethylation with increased E-cadherin expression in JEG-3 and JAR cells were observed. Demethylation treatment significantly restored E-cadherin expression, contributing to decreases in the motility and invasiveness of HTR-8/SVneo cells. Sense-methylated oligonucleotides (MONs) labelled with Cy5 and complementary to a region of the human CDH1 promoter were designed, with the cytosines in 5'-cytosine-phosphate-guanine-3' (CpG) dinucleotides being replaced by methylated cytosines. Following MON transfection into JEG-3 cells, the level of CDH1 promoter DNA methylation as well as cell motility and invasiveness were increased and gene expression was significantly repressed. Our results indicate that MON-mediated DNA methylation of the CDH1 promoter and subsequent alterations in gene expression may contribute to trophoblast motility and invasion, suggesting a potential method for controlling the biological function of trophoblasts in vitro through epigenetic modification.

Silicon three-dimensional structures fabricated by femtosecond laser modification with dry etching.

In this paper, a maskless, high efficiency, and flexible technology is developed to fabricate three-dimensional (3D) microstructures on a silicon wafer, which is based on the combination of femtosecond laser modification and subsequent dry etching. The silicon atoms in 2D patterned areas were insufficiently oxidized after femtosecond laser irradiation. Complex 3D structures can be fabricated on the silicon wafer after etching, such as micro gears, comb drive actuators, and micro cantilevers applied in microelectromechanical systems (MEMS) and micro Fresnel zone plates applied in micro optics. What is more, surface roughness of the laser structured wafer can be improved with increased etching time in the dry etching process. This technology shows its unique capacity to fabricate various 3D microstructures for applications in MEMS and micro optics.

nm23 regulates decidualization through the PI3K-Akt-mTOR signaling pathways in mice and humans.

STUDY QUESTION: Does nm23 have functional significance in decidualization in mice and humans? SUMMARY ANSWER: nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs. WHAT IS KNOWN ALREADY: The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation. STUDY DESIGN, SIZE AND DURATION: We first analyzed the expression profile of nm23 in mice during early pregnancy (n = 6/group), pseudopregnancy (n = 6/group) and artificial decidualization (n = 6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways. PARTICIPANTS/MATERIALS, SETTINGS AND METHODS: We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot. MAIN RESULTS AND THE ROLE OF CHANCE: NM23-M1 was specifically expressed in the decidual zone during early pregnancy and in artificially induced deciduoma, and NM23-H1 was strongly expressed in human first trimester decidua. The expression of nm23 was upregulated by oestradiol and progesterone (P < 0.05 versus control) in vitro in mESCs and T-HESC, and this was inhibited by their respective receptor antagonists, ICI 182,780 and RU486. Mouse and human nm23 knockdown decreased ESC proliferation and differentiation (P < 0.05 versus control). The PI3K-Akt-mTOR signaling pathways were downstream mediators of nm23 in mESCs and T-HESCs decidualization. LIMITATIONS AND REASONS FOR CAUTION: Whether the nm23 regulates decidualization via the activation of AMPK, RAS, PKA, STAT3 or other signaling molecules remains to be determined. The role of nm23 in decidualization was tested in vitro only. WIDER IMPLICATIONS OF THE FINDINGS: Results demonstrate that nm23 plays a vital role in decidualization in mice and humans and that nm23 gene expression is hormonally regulated. The downregulation of nm23 in decidua during the first trimester may be associated with infertility in women. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (grant nos. 81370731, 31571551 and 31571190), the Science and Technology Project of Chongqing Education Committee (KJ130309), open funding by the Chongqing Institute for Family Planning (1201) and the Excellent Young Scholars of Chongqing Medical University (CQYQ201302). The authors have no conflicts of interest to declare.

Racial/ethnic disparities in human DNA methylation.

The racial/ethnic disparities in DNA methylation patterns indicate that molecular markers may play a role in determining the individual susceptibility to diseases in different ethnic groups. Racial disparities in DNA methylation patterns have been identified in prostate cancer, breast cancer and colorectal cancer and are related to racial differences in cancer prognosis and survival.