Looking beyond the Wnt pathway for the deep nature of β‐catenin

After two decades of stardom, one would think that β‐catenin has revealed all of its most intimate details. Yet the essence of its duality has remained mysterious—how can a single protein both be the core link between cadherins and the cytoskeleton, and the nuclear messenger for Wnt signalling? On the basis of the available evidence and on molecular and evolutionary considerations, I propose that β‐catenin was a born nuclear transport receptor, which by interacting with adhesion molecules acquired the property to coordinate nuclear functions with cell–cell adhesion. While Wnt signalling diverted this activity, the original pathway might still function in modern eukaryotes.     

Microfluidic synthesis of composite cross‐gradient materials for investigating cell–biomaterial interactions

Combinatorial material synthesis is a powerful approach for creating composite material libraries for the high‐throughput screening of cell–material interactions. Although current combinatorial screening platforms have been tremendously successful in identifying target (termed “hit”) materials from composite material libraries, new material synthesis approaches are needed to further optimize the concentrations and blending ratios of the component materials. Here we employed a microfluidic platform to rapidly synthesize composite materials containing cross‐gradients of gelatin and chitosan for investigating cell–biomaterial interactions. The microfluidic synthesis of the cross‐gradient was optimized experimentally and theoretically to produce quantitatively controllable variations in the concentrations and blending ratios of the two components. The anisotropic chemical compositions of the gelatin/chitosan cross‐gradients were characterized by Fourier transform infrared spectrometry and X‐ray photoelectron spectrometry. The three‐dimensional (3D) porous gelatin/chitosan cross‐gradient materials were shown to regulate the cellular morphology and proliferation of smooth muscle cells (SMCs) in a gradient‐dependent manner. We envision that our microfluidic cross‐gradient platform may accelerate the material development processes involved in a wide range of biomedical applications. Biotechnol. Bioeng. 2011; 108:175–185. © 2010 Wiley Periodicals, Inc.     

电针结合红外线照射对反复着床失败患者子宫内膜容受性、胚胎移植及妊娠情况的影响

目的:观察电针结合红外线照射对反复着床失败(RIF)患者子宫内膜容受性、胚胎移植及妊娠情况的影响。方法:选取102例于2015年5月-2018年5月在我院行复苏胚胎移植的RIF患者,按照随机数字表法将患者分为电针结合红外线照射治疗组(A组,38例)、安慰针刺组(B组,34例)及空白对照组(C组,30例)。比较三组治疗前后血清雌二醇、孕酮水平,于治疗前后检测子宫内膜容受性超声学指标,包括子宫内膜厚度、内膜容积、血管血流指数(VFI)、内膜血流指数(FI)、阻力指数(RI),比较三组胚胎移植及妊娠情况。结果:三组治疗前后血清雌二醇、孕酮水平比较无统计学差异(P0.05)。治疗后A组子宫内膜厚度、内膜容积大于治疗前及B组、C组,VFI、FI高于治疗前及B组、C组,RI低于治疗前及B组、C组(P0.05)。三组移植胚胎数、生化妊娠率、临床妊娠率比较无统计学差异(P0.05),A组胚胎着床率高于B组、C组(P0.05)。结论:电针结合红外线照射治疗RIF患者可以改善子宫内膜容受性,提高胚胎着床率。     

Laying the groundwork for growth: Cell–cell and cell–ECM interactions in cardiovascular development

Cardiac development is reliant upon the spatial and temporal regulation of both genetic and chemical signals. Central to the communication of these signals are direct interactions between cells and their surrounding environment. The extracellular matrix (ECM) plays an integral role in cell communication and tissue growth throughout development by providing both structural support and chemical signaling factors. The present review discusses elements of cell–cell and cell–ECM interactions involved in cardiogenesis, and how disruption of these interactions can result in numerous heart defects. Examining the relationships between cells and their immediate environment has implications for novel and existing therapeutic strategies to combating congenital disorders. Birth Defects Research (Part C) 90:1–7, 2010. © 2010 Wiley‐Liss, Inc.     

Proteomic Analysis of Stromal and Epithelial Cell Communications in Human Endometrial Cancer Using a Unique 3D Co‐Culture Model

Epithelial and stromal communications are essential for normal uterine functions and their dysregulation contributes to the pathogenesis of many diseases including infertility, endometriosis, and cancer. Although many studies have highlighted the advantages of culturing cells in 3D compared to the conventional 2D culture system, one of the major limitations of these systems is the lack of incorporation of cells from non‐epithelial lineages. In an effort to develop a culture system incorporating both stromal and epithelial cells, 3D endometrial cancer spheroids are developed by co‐culturing endometrial stromal cells with cancerous epithelial cells. The spheroids developed by this method are phenotypically comparable to in vivo endometrial cancer tissue. Proteomic analysis of the co‐culture spheroids comparable to human endometrial tissue revealed 591 common proteins and canonical pathways that are closely related to endometrium biology. To determine the feasibility of using this model for drug screening, the efficacy of tamoxifen and everolimus is tested. In summary, a unique 3D model system of human endometrial cancer is developed that will serve as the foundation for the further development of 3D culture systems incorporating different cell types of the human uterus for deciphering the contributions of non‐epithelial cells present in cancer microenvironment.     

子宫内膜容受性检测技术在反复种植失败患者冻融胚胎移植中的应用价值及其临床妊娠的影响因素分析

摘要 目的：探讨子宫内膜容受性检测（ERT）技术在反复种植失败患者冻融胚胎移植（FET）中的应用价值,并分析其临床妊娠的影响因素。方法：回顾性分析2019年10月~2022年4月期间海南省妇女儿童医学中心收治的150例反复种植失败患者的临床资料,根据是否接受ERT技术分为ERT组（n=78,接受ERT技术）和无ERT组（n=72,未接受ERT技术）。按照反复种植失败患者是否临床妊娠分为临床妊娠组和未临床妊娠组。采用单因素和多因素Logistic回归模型分析临床妊娠的影响因素。结果：两组异位妊娠率组间对比未见统计学差异（P>0.05）。ERT组临床妊娠率、活产率高于无ERT组,移植日内膜厚度大于无ERT组,移植胚胎数少于无ERT组,流产率低于无ERT组（P<0.05）。所有患者按照是否临床妊娠分为临床妊娠组（n=85）和未临床妊娠组（n=65）。单因素分析结果显示：临床妊娠与年龄、移植胚胎类别、移植胚胎数量、总周期数、FSH、子宫内膜厚度、子宫内膜类型有关（P<0.05）,而与体质量指数（BMI）、不孕年限、不孕类型、胚胎冷冻保存时间无关（P>0.05）。多因素Logistic回归分析结果显示：年龄偏大、FSH偏高是临床妊娠的危险因素,而移植胚胎类别为囊胚、移植胚胎数量偏多是临床妊娠的保护因素（P<0.05）。结论：ERT技术用于反复种植失败患者FET中,可有效改善患者的临床妊娠。年龄、FSH、移植胚胎类别、移植胚胎数量是临床妊娠的影响因素。     

Rhamnogalacturonan‐I is a determinant of cell–cell adhesion in poplar wood

The molecular basis of cell–cell adhesion in woody tissues is not known. Xylem cells in wood particles of hybrid poplar (Populus tremula × P. alba cv. INRA 717‐1B4) were separated by oxidation of lignin with acidic sodium chlorite when combined with extraction of xylan and rhamnogalacturonan‐I (RG‐I) using either dilute alkali or a combination of xylanase and RG‐lyase. Acidic chlorite followed by dilute alkali treatment enables cell–cell separation by removing material from the compound middle lamellae between the primary walls. Although lignin is known to contribute to adhesion between wood cells, we found that removing lignin is a necessary but not sufficient condition to effect complete cell–cell separation in poplar lines with various ratios of syringyl:guaiacyl lignin. Transgenic poplar lines expressing an Arabidopsis thaliana gene encoding an RG‐lyase (AtRGIL6) showed enhanced cell–cell separation, increased accessibility of cellulose and xylan to hydrolytic enzyme activities, and increased fragmentation of intact wood particles into small cell clusters and single cells under mechanical stress. Our results indicate a novel function for RG‐I, and also for xylan, as determinants of cell–cell adhesion in poplar wood cell walls. Genetic control of RG‐I content provides a new strategy to increase catalyst accessibility and saccharification yields from woody biomass for biofuels and industrial chemicals.     

Structure and Functions of Classical Cadherins

Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell–cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell–cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins.     

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial–embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, a trophectoderm spheroid‐based in vitro model mimicking the pre‐implantation human embryo is used to recapitulate important functional aspects of blastocyst implantation. Functionally, human endometrial EVs, derived from hormonally treated cells synchronous with implantation, are readily internalized by trophectoderm cells, regulating adhesive and invasive capacity of human trophectoderm spheroids. To gain molecular insights into mechanisms underpinning endometrial EV‐mediated enhancement of implantation, quantitative proteomics reveal critical alterations in trophectoderm cellular adhesion networks (cell adhesion molecule binding, cell–cell adhesion mediator activity, and cell adherens junctions) and metabolic and gene expression networks, and the soluble secretome from human trophectodermal spheroids. Importantly, transfer of endometrial EV cargo proteins to trophectoderm to mediate changes in trophectoderm function is demonstrated. This is highlighted by correlation among endometrial EVs, the trophectodermal proteome following EV uptake, and EV‐mediated trophectodermal cellular proteome, important for implantation. This work provides an understanding into molecular mechanisms of endometrial EV‐mediated regulation of human trophectoderm functions—fundamental in understanding human endometrium–embryo signaling during implantation.     

Above‐ and belowground biotic interactions facilitate relocation of plants into cooler environments

One important but largely unanswered question about floristic responses to climate change is how interactions such as competition, facilitation and plant–soil feedbacks will influence the ability of species to track shifting climates. In a rugged and moisture‐limited region that has recently warmed by 2° (Siskiyou Mountains, OR, USA), we planted three species into cooler aspects and elevations than those they currently inhabit, with and without removal of neighbouring plants, and tracked them over 2 years. Two species had higher success in cooler topographic locations, and this success was enhanced by neighbouring plants, which appeared to modulate minimum growing season temperatures. One species' success was also facilitated by the higher soil organic matter found in cooler sites. These results are a novel experimental demonstration of two important factors that may buffer climate change impacts on plants: rugged topography and plant–plant facilitation.     

Overexpression of the Xenopus Tight-Junction Protein Claudin Causes Randomization of the Left–Right Body Axis

This study presents Xenopus claudin (Xcla), a tight-junction protein that is abundantly expressed in eggs and neuroectodermal precursors during early development. It was isolated via a differential screen for mRNAs enriched in microsomes in the Xenopus blastula. The Xcla protein contains four transmembrane domains and a carboxy-terminal cytoplasmic region with a putative PDZ-binding site. We show that this PDZ-binding site of Xcla is critical for its correct localization on the cell membrane and that a truncated form leads to delocalization of the tight-junction protein ZO-1. Overexpression of Xcla causes changes in the cell adhesion properties of blastomeres and leads to visceral situs randomization. The results suggest that left–right axial patterning is very sensitive to changes in regulation of cell–cell interactions and implicate a tight-junction protein in the determination of left–right asymmetry.     

Polarity, Protrusion–Retraction Dynamics and Their Interplay during Keratinocyte Cell Migration

Keratinocyte migration on a two-dimensional substrate can be split into four distinct phases: cell extension, attachment, contraction, and detachment. It is preceded by polarization of the cell which leads to a functional asymmetry observable by the formation of a leading lamella. In this work variation of fibronectin coating concentrations and competitive inhibition with RGD peptides are used to investigate the dependency of polarization, migration, lamella dynamics, and ruffling on substrate adhesiveness. Looking at migrating human epidermal keratinocytes with a well-defined polarity we find that a fibronectin-coating concentration of 10 μg/cm² stimulates migration and ruffling speed twofold, whereas protrusion speed increases only by 20% (compared to 2.5 μg/cm² fibronectin). Nonpolar cells show a constant migration and ruffling speed independent of the amount of fibronectin. In contrast protrusion speeds of polar and nonpolar cells are equal. Treatment of cells on 10 μg/cm² fibronectin with 1 mg/ml GRGDS reduces the characteristic migration, protrusion, and ruffling speed of polar cells which corresponds to lowering the effective coating concentration to under 5 μg/cm². The probability of being polarized (quantified by a polarity index) increases with increasing fibronectin concentration. However, addition of soluble RGD on 10 μg/cm² fibronectin does not simply reduce the polarity index like one would expect from the corresponding changes in the other motility parameters, but it remains unchanged.