The eye lens is a transparent, ellipsoid tissue in the anterior chamber that is required for the fine focusing of light onto the retina to transmit a clear image. The focusing function of the lens is tied to tissue transparency, refractive index, and biomechanical properties. The stiffness and elasticity or resilience of the human lens allows for shape changes during accommodation to focus light from objects near and far. It has long been hypothesized that changes in lens biomechanical properties with age lead to the loss of accommodative ability and the need for reading glasses with age. However, the cellular and molecular mechanisms that influence lens biomechanical properties and/or change with age remain unclear. Studies of lens stiffness and resilience in mouse models with genetic defects or at advanced age inform us of the cytoskeletal, structural, and morphometric parameters that are important for biomechanical stability. In this review, we will explore whether: 1) tissue level changes, including the capsule, lens volume, and nucleus volume, 2) cellular level alterations, including cell packing, suture organization, and complex membrane interdigitations, and 3) molecular scale modifications, including the F-actin and intermediate filament networks, protein modifications, lipids in the cell membrane, and hydrostatic pressure, influence overall lens biomechanical properties.

Bone homeostasis is a complex process in which some Eph kinase receptors and their ephrin ligands appear to be involved. In the present study, we address this issue by examining, both in vitro and in vivo, the role of EphB2 and EphB3 in mesenchymal stromal/stem cell (MSC) differentiation into bone tissue. This was first evaluated by quantitative reverse transcription PCR (RT-qPCR) and histological staining in MSCs cultured in specific mediums revealing that although EphB2-/- MSCs mainly expressed pro-adipogenic transcription factors, EphB3-/- MSCs showed abundant osteogenic transcripts, such as Runx2, Msx2, and Sp7. To clarify the underlying molecular mechanisms, we found that the lack of EphB3 signaling alters the genetic profile of differentiating MSCs, reducing the expression of many inhibitory molecules and antagonists of the BMP signaling pathway, and increasing Bmp7 expression, a robust bone inductor. Then, to confirm the osteogenic role of EphB3 in vivo, we studied the condition of 2 mouse models of induced bone loss (ovariectomy or long-term glucocorticoid treatment). Interestingly, in both models, both WT and EphB2-/- mice equally developed the disease but EphB3-/- mice did not exhibit the typical bone loss, nor an increase in urine Ca2+ or blood serum CTX-1. This phenotype in EphB3-KO mice could be due to their significantly higher proportions of osteoprogenitor cells and preosteoblasts, and their lower number of osteoclasts, as compared with WT and EphB2-KO mice. Thus, we conclude that EphB3 acts as a negative regulator of the osteogenic differentiation, and its absence prevents bone loss in mice subjected to ovariectomy or dexamethasone treatment.
Osteoporosis affects more than 200 million people, mostly women. Our work shows that the EphB3 receptor restricts bone formation, and its absence prevents bone loss in osteoporotic mice. The bone protection observed in EphB3-deficient mice is due to the presence of more bone-forming cells and fewer bone-degrading cells. Molecularly, we found that when there’s no EphB3 in mesenchymal stem cells, some bone-promoting genes are increased while many inhibitors are reduced. Therefore, this receptor could become a key target for new therapies that would help to improve the quality of life for those suffering from bone diseases. We’re really excited to share our findings with a broad audience, including patients, healthcare professionals, researchers, and the life sciences industry.

Pediatric neoplasms represent a complex group of malignancies that pose unique challenges in terms of diagnosis, treatment, and understanding of the underlying molecular pathogenetic mechanisms. Erythropoietin-producing hepatocellular receptors (EPHs), the largest family of receptor tyrosine kinases and their membrane-tethered ligands, ephrins, orchestrate short-distance cell-cell signaling and are intricately involved in cell-pattern morphogenesis and various developmental processes. Unraveling the role of the EPH/ephrin signaling pathway in the pathophysiology of pediatric neoplasms and its clinical implications can contribute to deciphering the intricate landscape of these malignancies. The bidirectional nature of the EPH/ephrin axis is underscored by emerging evidence revealing its capacity to drive tumorigenesis, fostering cell-cell communication within the tumor microenvironment. In the context of carcinogenesis, the EPH/ephrin signaling pathway prompts a reevaluation of treatment strategies, particularly in pediatric oncology, where the modest progress in survival rates and enduring treatment toxicity necessitate novel approaches. Molecularly targeted agents have emerged as promising alternatives, prompting a shift in focus. Through a nuanced understanding of the pathway\'s intricacies, we aim to lay the groundwork for personalized diagnostic and therapeutic strategies, ultimately contributing to improved outcomes for young patients grappling with neoplastic challenges.

From the moment a cell is on the path to malignant transformation, its interaction with other cells from the microenvironment becomes altered. The flow of molecular information is at the heart of the cellular and systemic fate in tumors, and various processes participate in conveying key molecular information from or to certain cancer cells. For instance, the loss of tight junction molecules is part of the signal sent to cancer cells so that they are no longer bound to the primary tumors and are thus free to travel and metastasize. Upon the targeting of a single cell by a therapeutic drug, gap junctions are able to communicate death information to by-standing cells. The discovery of the importance of novel modes of cell-cell communication such as different types of extracellular vesicles or tunneling nanotubes is changing the way scientists look at these processes. However, are they all actively involved in different contexts at the same time or are they recruited to fulfill specific tasks? What does the multiplicity of modes mean for the overall progression of the disease? Here, we extend an open invitation to think about the overall significance of these questions, rather than engage in an elusive attempt at a systematic repertory of the mechanisms at play.

BACKGROUND: Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation, prevents the release of inflammatory molecules, and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remain ill-defined.
METHODS: We used GFP bone marrow chimeric knockout (KO) mice to demonstrate that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing MERTK in the brain to restrict efferocytosis of resident microglia and peripheral-derived monocyte/macrophages.
RESULTS: Single-cell RNAseq identified MERTK expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis and overall protein expression of p-MERTK, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to the wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with MERTK-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Selective inhibitors of ERK and Stat6 attenuated this effect, confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway.
CONCLUSIONS: Our findings implicate the ERK/Stat6/MERTK axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.

UNASSIGNED: Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation and prevents the release of inflammatory molecules and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remains ill-defined.
UNASSIGNED: We demonstrate using GFP bone marrow chimeric knockout (KO) mice, that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing Mertk signaling in the brain to restrict the function of efferocytosis on resident microglia and peripheral-derived monocyte/macrophages.
UNASSIGNED: Single-cell RNAseq identified Mertk expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis, and overall protein expression of p-Mertk, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with Mertk-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Select inhibitors of ERK and Stat6 attenuated this effect confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway.
UNASSIGNED: Our findings implicate the Mertk/ERK/Stat6 axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.

Surfactants can aid subsurface remediation through three primary mechanisms - solubilization, mobilization and/or emulsification. Among these mechanisms, emulsification in porous media is generally not well studied or well understood; particularly in the context of treating sources containing multicomponent NAPL. The objective of this research was to elucidate the processes responsible for recovery of a multicomponent hydrocarbon NAPL when surfactant solutions are introduced within a porous medium to promote the formation of kinetically-stable oil-in-water emulsions. Emulsifier formulations considered here were selected to offer similar performance characteristics while relying on different families of non-ionic surfactants - nonylphenol ethoxylates or alcohol ethoxylates - for emulsification. The families of surfactants have particular environment relevance, as alcohol ethoxylates are often used where replacement of nonylphenol content is necessary. Results from batch and column studies suggest performance of the two formulations was similar. With both, a synergistic combination of emulsification and mobilization led to recovery of a synthetic gasoline NAPL. The relative contribution of solubilization to the recovery was found to be minor. Moreover, the physical processes associated with emulsification and mobilization acted to limit the amount of preferential recovery (or fractionation) of the multicomponent NAPL.

Lung cancer (LC) is the leading cause of cancer death in the United States. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest receptor tyrosine kinases (RTKs) family in mammals. EPHs along with their ligands, EPH-family receptor-interacting proteins (ephrins), have been found to be either up- or downregulated in LC cells, hence exhibiting a defining role in LC carcinogenesis and tumor progression. In their capacity as membrane-bound molecules, EPHs/ephrins may represent feasible targets in the context of precision cancer treatment. In order to investigate available therapeutics targeting the EPH/ephrin system in LC, a literature review was conducted, using the MEDLINE, LIVIVO, and Google Scholar databases. EPHA2 is the most well-studied EPH/ephrin target in LC treatment. The targeting of EPHA2, EPHA3, EPHA5, EPHA7, EPHB4, EPHB6, ephrin-A1, ephrin-A2, ephrin-B2, and ephrin-B3 in LC cells or xenograft models not only directly correlates with a profound LC suppression but also enriches the effects of well-established therapeutic regimens. However, the sole clinical trial incorporating a NSCLC patient could not describe objective anti-cancer effects after anti-EPHA2 antibody administration. Collectively, EPHs/ephrins seem to represent promising treatment targets in LC. However, large clinical trials still need to be performed, with a view to examining the effects of EPH/ephrin targeting in the clinical setting.

OBJECTIVE: Emergency surgical procedures involve considerable risks. Among these, early postoperative hypoxemia (EPH) is a frequent anesthetic complication in the post-anesthetic care unit (PACU). There is a great concern for EPH among health professionals, specifically, those providing emergency surgery during the nighttime. This raised anesthesia-ended time-related risk of EPH question. Thus, this study aimed to determine the magnitude of EPH and its associated factors among adult patients who undergo emergency surgery under general anesthesia.
METHODS: A prospective observational study through a consecutive sampling technique was conducted. Binary logistic regression analysis was used to identify associated risk factors. All variables that were found statistically significant on bivariable analysis were entered into a multivariable logistic regression analysis.
RESULTS: Of 352 patients who had undergone emergency surgery, 149 (42.3%) patients developed EPH. Factors significantly associated with EPH were anesthesia ended during nighttime (AOR = 1.76, 95%CI [1.01, 3.05], p = 0.045), ASA III (AOR = 12.35, 95%CI: [4.5, 34.02], p ≤ 0.001), age greater than 55 (AOR = 3.2, 95%CI: [1.7, 5.91], p ≤ 0.001), surgery duration greater than 2 h (AOR = 2.012, 95%CI: [1.2, 3.51], p = 0.014), hypotension (AOR = 10.3, 95%CI: [2.4, 44.16], p = 0.002), muscular strength score zero (AOR = 2.944, 95%CI: [1.8, 4.82], p ≤ 0.001), and preoperative oxygen saturation less than 95% (AOR = 2.371, 95%CI: [1.35,4.16], p = 0.003).
CONCLUSIONS: The magnitude of EPH among patients who have undergone emergency surgery was high and thus recommended that oxygen should be provided timely to decrease it. Identified risk factors were night-time ended anesthesia, ASA III, age greater than 55, surgery duration greater than 2 h, hypotension, muscular strength score zero, and preoperative oxygen saturation less than 95%. This study found anesthesia ended during early morning favors early morning early postoperative hypoxemia (EMEPH). To avert EMEPH, the anesthetist should avoid factors that favor the circadian rhythm of the lung-based early morning anesthesia augmented EPH.

Kupffer cells are maintained via self-renewal in specific microenvironmental niches, primarily the liver sinusoidal endothelial cells (LSECs). In this study, we propagated tissue-resident macrophages (Mø) from mouse liver using mixed culture with hepatic fibroblastic cells. Propagated liver Mø express Id3, Lxra and Spic transcription factors, which are required for Kupffer cell characterization. Thus, Kupffer cell properties are likely to be maintained in liver Mø propagated using mixed culture with fibroblastic cells. We revealed (i) gene expression of certain Eph receptors and ephrin ligands including EphA2, ephrin-A1, EphB4, and ephrin-B1 in propagated liver Mø and primary LSECs, (ii) immunohistochemical localization of these Eph/ephrin member molecules indicating common expression in Kupffer cells and LSECs, and (iii) surface expression of several integrin α and β subunits, including α4β1, αLβ2, αMβ2, and αXβ2 integrin in propagated liver Mø and that of the corresponding ligands ICAM-1 and VCAM-1 in primary LSECs. Moreover, EphA/ephrin-A and EphB/ephrin-B interactions promoted liver Mø adhesion to the ICAM-1-adsorbed surface, which mimicked that of LSECs and may be implicated in the residence of Kupffer cells in the liver sinusoid. Further studies on regulating the residence and regeneration of Kupffer cells in related hepatic disorders are required to validate our findings.