Evidence for coopetition at the maternal-fetal interface shaping placental invasion.

Coopetition is a term from game theory that describes a mix of cooperative and competitive behavior. The maternal-fetal interface (MFI) among eutherian mammals presents close interaction of two distinct individuals. These interactions have resulted in a remarkable diversity in MFI structure, often interpreted as the outcome of maternal-fetal conflict.

Identifying genes underlying parallel evolution of stromal resistance to placental and cancer invasion.

Stromal regulation of cancer dissemination is well recognized, however causal genes remain unidentified. We previously demonstrated that epitheliochorial species have acquired stromal resistance to placental invasion, correlating with reduced rate of cancer malignancies, identifying stromal genes correlating with depth of placental invasion called ELI (Evolved Levels of Invasibility) genes. Similarly, decidualization of human endometrial fibroblasts confers resistance to placental invasion.

Stable and oscillatory hypoxia differentially regulate invasibility of breast cancer associated fibroblasts.

As local regions in the tumor outstrip their oxygen supply, hypoxia can develop, affecting not only the cancer cells, but also other cells in the microenvironment, including cancer associated fibroblasts (CAFs). Hypoxia is also not necessarily stable over time, and can fluctuate or oscillate. Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia, and can also exhibit oscillations in its activity.

PIEZO1 Activation-Mediated Generation of Transgene-Free Long-Term Hematopoietic Stem Cells.

The development of engraftable, long-term reconstituting hematopoietic stem cells (LT-HSC) from human pluripotent stem cells (hPSC) has been a long-sought goal. Since HSCs are formed by a subset of endothelial cells in the ventral part of the dorsal aorta, we analyzed heartbeat-mediated pulsatile displacement experienced by the walls of the dorsal aorta in zebrafish embryos. We found that pulsation-mediated circumferential stretch was restricted to the ventral part of the dorsal aorta and activated Piezo1 to stimulate LT-HSC formation.

Extravillous trophoblasts reverse the decidualization induced increase in matrix production by secreting TGFβ antagonists Emilin-1 and Gremlin-1.

The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma.

Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients.

Hypoxia is one of the key factors in the tumor microenvironment regulating nearly all steps in the metastatic cascade in many cancers, including in breast cancer. The hypoxic regions can however be dynamic with the availability of oxygen fluctuating or oscillating. The canonical response to hypoxia is relayed by transcription factor Hypoxia-Inducible Factor 1 (HIF-1), which is stabilized in hypoxia and acts as the master regulator of a large number of downstream genes.

Stable and Oscillatory Hypoxia Differentially Regulate Invasibility of Breast Cancer Associated Fibroblasts.

As local regions in the tumor outstrip their oxygen supply, hypoxia can develop, affecting not only the cancer cells, but also other cells in the microenvironment, including cancer associated fibroblasts (CAFs). Hypoxia is also not necessarily stable over time, and can fluctuate or oscillate. Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia, and can also exhibit oscillations in its activity.

Development of a prognostic model for lung adenocarcinoma polarity-related genes and analysis of immune landscape.

Despite the progress made in the management of lung adenocarcinoma (LUAD), the overall prognosis for LUAD individuals remains suboptimal. While the role of cell polarity in tumor invasion and metastasis is well established, its prognostic significance in LUAD is still unknown. Differential analysis was performed on the Cancer Genome Atlas (TCGA)-LUAD and normal lung tissue, and candidate genes were identified by intersecting differentially expressed genes with polarity-related genes (PRGs).

Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells.

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content in the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited to breast cancer by many mechanisms, including hypoxia, and contribute to metastatic transition of the cancer. Breast cancers are characterized by regions of hypoxia, which can be temporally unstable owing to a mismatch between oxygen supply and consumption.

Oscillatory Hypoxia Induced Unfolded Protein Folding Response Gene Expression Predicts Low Survival in Human Breast Cancer Patients.

Hypoxia is one of the key factors in the tumor microenvironment regulating nearly all steps in the metastatic cascade in many cancers, including in breast cancer. The hypoxic regions can however be dynamic with the availability of oxygen fluctuating or oscillating. The canonical response to hypoxia is relayed by transcription factor HIF-1, which is stabilized in hypoxia and acts as the master regulator of a large number of downstream genes.

Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale.

Introduction: Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.

Methods: The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale.

Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNFα-Stimulated NFκB Activity and FAT10 Expression in Human Corneal Epithelial Cells.

Dry Eye Disease (DED) is a complex pathology affecting millions of people with significant impact on quality of life. Corneal inflammation, including via the nuclear factor kappa B (NFκB) pathway, plays a key etiological role in DED. Recombinant human proteoglycan 4 (rhPRG4) has been shown to be a clinically effective treatment for DED that has anti-inflammatory effects in corneal epithelial cells, but the underlying mechanism is still not understood.

Paracrine HB-EGF signaling reduce enhanced contractile and energetic state of activated decidual fibroblasts by rebalancing SRF-MRTF-TCF transcriptional axis.

Multiple parallels exist between placentation and cancer dissemination at molecular, cellular, and anatomical levels, presenting placentation as a unique model to mechanistically understand the onset of cancer metastasis. In humans, interaction of placenta and the endometrium results eventually in deep invasion of placental extravillous trophoblasts (EVTs) into the maternal stroma, a process similar to stromal trespass by disseminating carcinoma cells. In anticipation of implantation, endometrial fibroblasts (ESFs) undergo a process called decidualization during the secretory phase of the menstrual cycle.

Cardiac ultrastructure inspired matrix induces advanced metabolic and functional maturation of differentiated human cardiomyocytes.

The vast potential of human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) in preclinical models of cardiac pathologies, precision medicine, and drug screening remains to be fully realized because hiPSC-CMs are immature without adult-like characteristics. Here, we present a method to accelerate hiPSC-CM maturation on a substrate, cardiac mimetic matrix (CMM), mimicking adult human heart matrix ligand chemistry, rigidity, and submicron ultrastructure, which synergistically mature hiPSC-CMs rapidly within 30 days. hiPSC-CMs matured on CMM exhibit systemic transcriptomic maturation toward an adult heart state, are aligned with high strain energy, metabolically rely on oxidative phosphorylation and fatty acid oxidation, and display enhanced redox handling capability, efficient calcium handling, and electrophysiological features of ventricular myocytes.

Mesenchymal stem cells-derived extracellular vesicles containing miR-378a-3p inhibit the occurrence of inflammatory bowel disease by targeting GATA2.

This study sought to determine whether mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) carrying microRNA-378a-3p (miR-378a-3p) could affect the pathogenesis of inflammatory bowel disease (IBD) by regulating the GATA-binding protein 2 (GATA2)/aquaporin-4 (AQP4)/peroxisome proliferator-activated receptor α (PPAR-α) axis. Initially, colon mucosa biopsy tissues were harvested from healthy controls and patients with IBD for qRT-PCR and immunohistochemistry analysis. EVs harvested from MSCs and lipopolysaccharide (LPS) were used to stimulate the M064 cells to establish an in vitro inflammation cell model.

Targeting p21 highly expressing cells in adipose tissue alleviates insulin resistance in obesity.

Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21 highly expressing (p21) cells, which accumulate in adipose tissue with obesity.

Research on the influence of heat treatment on residual stress of TC4 alloy produced by laser additive manufacturing based on laser ultrasonic technique.

During the laser additive manufacturing (LAM) process large temperature gradients can lead to high level of residual stress. The residual stress can have irreversible effects such as warping and cracking of parts during and post manufacturing. Heat treatment is an effective method to control and eliminate residual stress.

Peroxo Species Formed in the Bulk of Silicate Cathodes.

Oxygen redox in Li-rich oxides may boost the energy density of lithium-ion batteries by incorporating oxygen chemistry in solid cathodes. However, oxygen redox in the bulk usually entangles with voltage hysteresis and oxygen release, resulting in a prolonged controversy in literature on oxygen transformation. Here, we report spectroscopic evidence of peroxo species formed and confined in silicate cathodes amid oxygen redox at high voltage, accompanied by Co /Co redox dominant at low voltage.

Molecularly imprinted polymer solid phase extraction coupled with liquid chromatography-high resolution mass spectrometry for the detection of gonyautoxins 2&3 in seawater.

Paralytic shellfish toxins (PSTs) cause risks to human health through food chains. Understanding the change of PSTs in seawater is critical for predicting the safety of seafood. Most reported methods for the detection of PSTs in microalgae or shellfish are not applicable in seawater because of extremely low concentration and matrix interferences.

Nanostructure and its effect on electrochemical properties of polyanionic LiCoSiO for lithium ion batteries.

This work reports a facile strategy to synthesize carbon-coated LiCoSiO/C particles with rich nanostructures by a two-step scheme starting with a low-temperature hydrothermal method. The size and morphology of particle aggregates can be regulated by the (OH) concentration and viscosity of the precursor solution, a mixture of ethylene glycol and deionized water, for the hydrothermal synthesis. In addition to the good electrical conductivity from the carbon coating, the size of the primary nanoparticles and the mesopore associated with the aggregations play an important role in improving the electrochemical properties of polyanionic LiCoSiO.

Uniaxial Stretching of Cell-Laden Microfibers for Promoting C2C12 Myoblasts Alignment and Myofibers Formation.

Fiber-shaped cellular constructs have attracted increasing attention in the regeneration of blood vessels, nerve networks, and skeletal myofibers. Nevertheless, the generation of functional fiber-shaped cellular constructs suffers from limited appropriate microfiber-based fabrication approaches and the maintenance of regenerated tissue functions. Herein, we demonstrate a silicone-tube-based coagulant bath free method to fabricate tens of centimeters long cell-laden microfibers using single UV exposure without pretreatment of nozzles or microchannels.

Directed Collective Cell Migration Using Three-Dimensional Bioprinted Micropatterns on Thermoresponsive Surfaces for Myotube Formation.

Directed collective cell migration governs cell orientation during tissue morphogenesis, wound healing, and tumor metastasis. Unfortunately, current methods for initiating collective cell migration, such as scratching, laser ablation, and stencils, either introduce uncontrolled cell-injury, involve multiple fabrication processes, or have utility limited to cells with strong cell-cell junctions. Using three-dimensional (3D) bioprinted gelatin methacryloyl (GelMA) micropatterns on temperature-responsive poly(-isopropylacrylamide) (PNIPAm) coated interfaces, we demonstrate that directed injury-free collective cell migration could occur in parallel and perpendicular directions.

Arch-like microsorters with multi-modal and clogging-improved filtering functions by using femtosecond laser multifocal parallel microfabrication.

Conventional micropore membranes based size sorting have been widely applied for single-cell analysis. However, only a single filtering size can be achieved and the clogging issue cannot be completely avoided. Here, we propose a novel arch-like microsorter capable of multimodal (high-, band- and low-capture mode) sorting of particles.