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We present a robust strategy to numerically sample the Coulomb potential in reciprocal space for periodic Born–von Karman cells of general shape. Our approach tackles two common issues of plane-wave based implementations of Coulomb integrals under periodic boundary conditions: the treatment of the singularity at the Brillouin-zone center and discretization errors, which can cause severe convergence problems in anisotropic cells, necessary for the calculation of low-dimensional systems. We apply our strategy to the Hartree–Fock and coupled cluster (CC) theories and discuss the consequences of different sampling strategies on different theories. We show that sampling the Coulomb potential via the widely used probe-charge Ewald method is unsuitable for CC calculations in anisotropic cells. To demonstrate the applicability of our developed approach, we study two representative, low-dimensional use cases: the infinite carbon chain, for which we report the first periodic CCSD(T) potential energy surface, and a surface slab of lithium hydride, for which we demonstrate the impact of different sampling strategies for calculating surface energies. We find that our Coulomb sampling strategy serves as a vital solution, addressing the critical need for improved accuracy in plane-wave based CC calculations for low-dimensional systems. [ABSTRACT FROM AUTHOR]

Axonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect. Sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1) regulates several cell responses to axonal damage and has been implicated in promoting neuronal degeneration. SARM1 inhibition seems to result in protection from neuronal degeneration while hydrogen peroxide has been implicated in oxidative stress and axonal degeneration. The effects of laser-induced axonal damage in wild-type and HD dorsal root ganglion cells treated with NAm, hydrogen peroxide (H2 O2 ), and SARM1 inhibitor DSRM-3716 were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser-induced injury were measured.

The occurrence of atrial fibrillation (AF), one of the most socially significant arrhythmias, is associated with the presence of areas of fibrosis. Fibrosis introduces conduction heterogeneity into the cardiac tissue and, thus, may be a substrate for spiral wave reentry, which provokes the onset of AF and is often associated with its persistence. Despite results from computer and animal models of cardiac tissues, data on the conditions under which microreentries occur in human tissues are limited. In this work, we conducted a study of the new approach to modeling the fibrous atrial tissue, which takes into account the cellular structure and conduction in fibrosis areas. Using the Potts model, we created a realistic texture of atrial tissues remodeled by fibroblasts and showed the presence of pathways in such a system with a low proportion of fibroblasts. Our study revealed the relationship between the shape of the cells' action potential, their location in the tissue, and the direction of the wave propagation. The wavefront obtained in the model creates a dynamic heterogeneity of the tissue, which affects the migration and pinning of spiral waves, and explains the formation of microreentries in the cardiac tissue. In the future, such a model can become a potential tool for predictive modeling of AF and the search for ablation target identification. [ABSTRACT FROM AUTHOR]

Objectives: This article focuses on the detection of cells in low-contrast brightfield microscopy images; in our case, it is chronic lymphocytic leukaemia cells. The automatic detection of cells from brightfield time-lapse microscopic images brings new opportunities in cell morphology and migration studies; to achieve the desired results, it is advisable to use state-of-the-art image segmentation methods that not only detect the cell but also detect its boundaries with the highest possible accuracy, thus defining its shape and dimensions. Methods: We compared eight state-of-the-art neural network architectures with different backbone encoders for image data segmentation, namely U-net, U-net++, the Pyramid Attention Network, the Multi-Attention Network, LinkNet, the Feature Pyramid Network, DeepLabV3, and DeepLabV3+. The training process involved training each of these networks for 1000 epochs using the PyTorch and PyTorch Lightning libraries. For instance segmentation, the watershed algorithm and three-class image semantic segmentation were used. We also used StarDist, a deep learning-based tool for object detection with star-convex shapes. Results: The optimal combination for semantic segmentation was the U-net++ architecture with a ResNeSt-269 background with a data set intersection over a union score of 0.8902. For the cell characteristics examined (area, circularity, solidity, perimeter, radius, and shape index), the difference in mean value using different chronic lymphocytic leukaemia cell segmentation approaches appeared to be statistically significant (Mann–Whitney U test, P <.0001). Conclusion: We found that overall, the algorithms demonstrate equal agreement with ground truth, but with the comparison, it can be seen that the different approaches prefer different morphological features of the cells. Consequently, choosing the most suitable method for instance-based cell segmentation depends on the particular application, namely, the specific cellular traits being investigated. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency was also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection. Author summary: Urinary tract infections (UTIs) are one of the most common bacterial infections worldwide with 50% of women suffering from a UTI during their lifetime. Escherichia coli is the primary bacteria responsible for UTIs and is usually found in short rod forms. However, during UTIs E. coli can elongate into extremely long thin shapes called 'filaments'. Filaments are thought to be advantageous during infections because they are too long to be engulfed and killed by immune cells called macrophages. Due to increasing antibiotic resistance in bacteria there is a strong need for the discovery of new ways to treat infections and this is only possible once we thoroughly understand the mechanisms bacteria employ to overcome our immune response. Therefore, we investigated the effect of E. coli filamentation on macrophage engulfment along with other aspects of bacteria reported to influence engulfment. We found that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, surface and external environmental factors. Our research has highlighted the importance of bacterial shape changes during infections and provided a foundational understanding of macrophage engulfment of filaments. Eventually, this knowledge may reveal new targets for treatment of infections. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is a complex disease that significantly contributes to recurrent retinal detachment. Its development is notably affected by epithelial–mesenchymal transition (EMT), where apoptosis plays a crucial role as a regulator of EMT. However, the function of MeCP2 in governing apoptosis and EMT in retinal pigment epithelial (RPE) cells and its implications for PVR development have remained inadequately understood. Thus, we investigated the impact of MeCP2 on proliferation, migration, apoptosis and EMT in ARPE‐19 cells to provide a fresh perspective on the etiology of PVR. The morphological changes in ARPE‐19 cells induced by recombinant human MeCP2 protein and MeCP2 knockdown were observed. Wound healing assay were performed to verify the effects of recombinant human MeCP2 protein and MeCP2 knockdown on ARPE‐19 cell migration. Furthermore, cell proliferation was assessed using the CCK‐8 assay and flow cytometry. Western blot analysis, quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), and immunofluorescence analysis were conducted to measure the protein levels associated with apoptosis, cell cycle and EMT. Western blot analysis and immunofluorescence assays confirmed that MeCP2 promoted EMT formation in ARPE‐19 cells. The CCK‐8 assay revealed that MeCP2 treatment enhanced the proliferation of ARPE‐19 cells, whereas MeCP2 knockdown inhibited ARPE‐19 cell proliferation. Treatment with recombinant human MeCP2 protein and MeCP2 knockdown altered the morphology of ARPE‐19 cells. Wound healing assay demonstrated that MeCP2 knockdown inhibited ARPE‐19 cell migration, and MeCP2 treatment promoted ARPE‐19 cell migration. MeCP2 knockdown induced a G0/G1 phase block, inhibiting cell growth, and qRT‐PCR data indicated reduced expression of cell cycle‐related genes. Increased apoptosis was observed after MeCP2 knockdown in ARPE‐19 cells. Overall, MeCP2 treatment stimulates cell proliferation, migration and EMT formation; conversely, MeCP2 knockdown inhibits EMT, cell proliferation, migration and cell cycle G1/S phase transition, and induces apoptosis. [ABSTRACT FROM AUTHOR]

Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye. The ommatidium is shaped as a hexagonal prism, and generating this 3D structure requires ommatidial cells to adopt specific apical and basal polygonal geometries. Using this model system, we find that generating cell type–specific basal geometries starts with patterning of the basal extracellular matrix, whereby Laminin accumulates at discrete locations across the basal surface of the retina. We find the Dystroglycan receptor complex (DGC) is required for this patterning by promoting localized Laminin accumulation at the basal surface of cells. Moreover, our results reveal that localized accumulation of Laminin and the DGC are required for directing Integrin adhesion. This induces cell basal geometry remodeling by anchoring the basal surface of cells to the extracellular matrix at specific, Laminin-rich locations. We propose that patterning of a basal extracellular matrix by generating discrete Laminin domains can direct Integrin adhesion to induce cell shape remodeling in epithelial morphogenesis. Cell shape remodeling is a main driver of epithelial tissue morphogenesis, but how cell basal geometry is regulated remains unclear. This work identifies a novel morphogenetic pathway involving laminin and integrin adhesion that coordinates the remodelling of epithelial cell shape by patterning their basement membrane. [ABSTRACT FROM AUTHOR]

Background: Inflammation-induced testicular damage is a significant contributing factor to the increasing incidence of infertility. Traditional treatments during the inflammatory phase often fail to achieve the desired fertility outcomes, necessitating innovative interventions such as cell therapy. Methods: We explored the in vivo properties of intravenously administered Sertoli cells (SCs) in an acute lipopolysaccharide (LPS)-induced inflammatory mouse model. Infiltrating and resident myeloid cell phenotypes were assessed using flow cytometry. The impact of SC administration on testis morphology and germ cell quality was evaluated using computer-assisted sperm analysis (CASA) and immunohistochemistry. Results: SCs demonstrated a distinctive migration pattern, importantly they preferentially concentrated in the testes and liver. SC application significantly reduced neutrophil infiltration as well as preserved the resident macrophage subpopulations. SCs upregulated MerTK expression in both interstitial and peritubular macrophages. Applied SC treatment exhibited protective effects on sperm including their motility and kinematic parameters, and maintained the physiological testicular morphology. Conclusion: Our study provides compelling evidence of the therapeutic efficacy of SC transplantation in alleviating acute inflammation-induced testicular damage. These findings contribute to the expanding knowledge on the potential applications of cell-based therapies for addressing reproductive health challenges and offer a promising approach for targeted interventions in male infertility. [ABSTRACT FROM AUTHOR]

Genomics methods have uncovered patterns in a range of biological systems, but obscure important aspects of cell behavior: the shapes, relative locations, movement, and interactions of cells in space. Spatial technologies that collect genomic or epigenomic data while preserving spatial information have begun to overcome these limitations. These new data promise a deeper understanding of the factors that affect cellular behavior, and in particular the ability to directly test existing theories about cell state and variation in the context of morphology, location, motility, and signaling that could not be tested before. Rapid advancements in resolution, ease-of-use, and scale of spatial genomics technologies to address these questions also require an updated toolkit of statistical methods with which to interrogate these data. We present a framework to respond to this new avenue of research: four open biological questions that can now be answered using spatial genomics data paired with methods for analysis. We outline spatial data modalities for each open question that may yield specific insights, discuss how conflicting theories may be tested by comparing the data to conceptual models of biological behavior, and highlight statistical and machine learning-based tools that may prove particularly helpful to recover biological understanding. [ABSTRACT FROM AUTHOR]

The spatial arrangement of immune cells within the tumor microenvironment (TME) and their interactions play critical roles in the initiation and development of cancer. Several advanced technologies such as imaging mass cytometry (IMC) providing the immunological landscape of the TME with single-cell resolution. In this study, we develop a new method to quantify the spatial proximity between different cell types based on single-cell spatial data. Using this method on IMC data from 416 lung adenocarcinoma patients, we show that the proximity between different cell types is more correlated with patient prognosis compared to the traditional features such immune cell density and fractions. Consistent with previous reports, our results validate that proximity of T helper (Th) and B cells to cancer cells is associated with survival benefits. More importantly, we discover that the proximity of M2 macrophages to multiple immune cells is associated with poor prognosis. When Th/B cells are stratified into M2-distal and M2-proximal, the abundance of the former but not the latter category of Th/B cells is correlated with enhanced patient survival. Additionally, the abundance of M2-distal and M2-proximal cytotoxic T cells (Tc) is respectively associated with good and poor prognosis. Our results indicate that the prognostic effect of Th, Tc, and B cells in the tumor microenvironment is modulated by the nearby M2 macrophages. The proposed new method proposed can be readily applied to all single-cell spatial data for revealing functional impact of immune cell interactions. [ABSTRACT FROM AUTHOR]

Spatially nonlinear stimulus integration by retinal ganglion cells lies at the heart of various computations performed by the retina. It arises from the nonlinear transmission of signals that ganglion cells receive from bipolar cells, which thereby constitute functional subunits within a ganglion cell's receptive field. Inferring these subunits from recorded ganglion cell activity promises a new avenue for studying the functional architecture of the retina. This calls for efficient methods, which leave sufficient experimental time to leverage the acquired knowledge for further investigating identified subunits. Here, we combine concepts from super-resolution microscopy and computed tomography and introduce super-resolved tomographic reconstruction (STR) as a technique to efficiently stimulate and locate receptive field subunits. Simulations demonstrate that this approach can reliably identify subunits across a wide range of model variations, and application in recordings of primate parasol ganglion cells validates the experimental feasibility. STR can potentially reveal comprehensive subunit layouts within only a few tens of minutes of recording time, making it ideal for online analysis and closed-loop investigations of receptive field substructure in retina recordings. Author summary: Neural computations in sensory systems often involve nonlinear pooling of sensory information. In the vertebrate retina, nonlinear signal transmission between bipolar cells and downstream ganglion cells, the output neurons of the retina, shapes the ganglion cells' functional properties and structures a ganglion cell's receptive field into smaller subunits. Methods for identifying these subunits from recordings of ganglion cell activity are needed to better understand the signal flow and the computations occurring between bipolar and ganglion cells. We here show that concepts from super-resolution microscopy and tomography can be used to design a visual stimulus and corresponding analysis to efficiently trigger ganglion cell activity while maintaining high spatial resolution for revealing subunits. As demonstrated by computer simulations and recordings from the primate retina, the method can identify subunit layouts with little experimental recording time, providing for the possibility to be combined with in-depth functional analyses or applied in closed-loop experiments. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs). Methods: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group. Results: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue. Conclusions: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype. [ABSTRACT FROM AUTHOR]

Metamonads are a large and exclusively anaerobic group of protists. Additionally, they are one of the three clades proposed to ancestrally possess an “excavate” cell morphology, with a conspicuous ventral groove accompanied by a posterior flagellum with a vane. Here, we cultivate and characterize four anaerobic bacterivorous flagellates from hypersaline and alkaline soda lake environments, which represent a novel clade. Small subunit ribosomal RNA (SSU rRNA) gene phylogenies support recent phylogenomic analyses in placing them as the sister of barthelonids, a group that is itself sister to or deeply branching within Fornicata (Metamonada). The new isolates have a distinctive morphology: the hunchbacked cell body is traversed by a narrow ventral groove ending in a large opening to a conspicuous recurrent cytopharynx. The right margin of the groove is defined by a thin “lip.” The posterior flagellum bears a wide ventral‐facing vane. The narrow ventral groove and elongate cytopharynx are shared with barthelonids. We describe one isolate as Skoliomonas litria, gen. et sp. nov. Further investigation of their mitochondrial‐related organelles (MROs) and detailed ultrastructural studies would be important to understanding the adaptation to anaerobic conditions in Metamonads—especially fornicates—as well as the evolution of the “excavate” cell architecture. [ABSTRACT FROM AUTHOR]

Curved cell shapes are widespread among bacteria and important for cellular motility, virulence and fitness. However, the underlying morphogenetic mechanisms are still incompletely understood. Here, we identify an outer-membrane protein complex that promotes cell curvature in the photosynthetic species Rhodospirillum rubrum. We show that the R. rubrum porins Por39 and Por41 form a helical ribbon-like structure at the outer curve of the cell that recruits the peptidoglycan-binding lipoprotein PapS, with PapS inactivation, porin delocalization or disruption of the porin-PapS interface resulting in cell straightening. We further demonstrate that porin-PapS assemblies act as molecular cages that entrap the cell elongation machinery, thus biasing cell growth towards the outer curve. These findings reveal a mechanistically distinct morphogenetic module mediating bacterial cell shape. Moreover, they uncover an unprecedented role of outer-membrane protein patterning in the spatial control of intracellular processes, adding an important facet to the repertoire of regulatory mechanisms in bacterial cell biology. Curved cell shapes are common among bacteria, but the underlying morphogenetic mechanisms are incompletely understood. Here, the authors identify an outer-membrane protein complex that promotes cell curvature in Rhodospirillum rubrum by forming helical ribbon structures that modulate the dynamics of cell wall biosynthesis, biasing cell growth towards the cell's outer curve. [ABSTRACT FROM AUTHOR]

Background β-lactam antibiotics, which inhibit penicillin-binding protein 3 (PBP3) that is required for cell division, play a key role in treating P. aeruginosa infections. Some sequence variations in PBP3 have been associated with β-lactam resistance but the effects of variations on antibiotic susceptibility and on cell division have not been quantified. Antibiotic efflux can also reduce susceptibility. Objectives To quantify the effects of PBP3 variations on β-lactam susceptibility and cell morphology in P. aeruginosa. Methods Nineteen PBP3 variants were expressed from a plasmid in the reference strain P. aeruginosa PAO1 and genome engineering was used to construct five mutants expressing PBP3 variants from the chromosome. The effects of the variations on β-lactam minimum inhibitory concentration (MIC) and cell morphology were measured. Results Some PBP3 variations reduced susceptibility to a variety of β-lactam antibiotics including meropenem, ceftazidime, cefepime and ticarcillin with different variations affecting different antibiotics. None of the tested variations reduced susceptibility to imipenem or piperacillin. Antibiotic susceptibility was further reduced when PBP3 variants were expressed in mutant bacteria overexpressing the MexAB-OprM efflux pump, with some variations conferring clinical levels of resistance. Some PBP3 variations, and sub-MIC levels of β-lactams, reduced bacterial growth rates and inhibited cell division, causing elongated cells. Conclusions PBP3 variations in P. aeruginosa can increase the MIC of multiple β-lactam antibiotics, although not imipenem or piperacillin. PBP3 variations, or the presence of sub-lethal levels of β-lactams, result in elongated cells indicating that variations reduce the activity of PBP3 and may reduce bacterial fitness. [ABSTRACT FROM AUTHOR]

The prevalence of pyramidal cells (PCs) in the mammalian cerebral cortex underscore their value as they play a crucial role in various brain functions, ranging from cognition, sensory processing, to motor output. PC morphology significantly influences brain connectivity and plays a critical role in maintaining normal brain function. Pathological alterations to PC morphology are thought to contribute to the aetiology of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. This review explores the relationship between abnormalities in PC morphology in key cortical areas and the clinical manifestations in schizophrenia and ASD. We focus largely on human postmortem studies and provide evidence that dendritic segment length, complexity and spine density are differentially affected in these disorders. These morphological alterations can lead to disruptions in cortical connectivity, potentially contributing to the cognitive and behavioural deficits observed in these disorders. Furthermore, we highlight the importance of investigating the functional and structural characteristics of PCs in these disorders to illuminate the underlying pathogenesis and stimulate further research in this area. [ABSTRACT FROM AUTHOR]

Reduced bone mass and degeneration of the microarchitecture of bone tissue are the hallmarks of osteoporosis, a bone metabolic disease that increases skeletal fragility and fracture susceptibility. Osteoporosis is primarily caused by unbalanced bone remodeling, in which bone synthesis is outpaced by bone resorption caused by osteoclasts. Along with the bone-building vitamins calcium and vitamin D, typical medications for treating osteoporosis include bisphosphonates and calcitonin. The present therapies effectively stop osteoclast activation that is too high, however they come with varying degrees of negative effects. Numerous factors can contribute to osteoporosis, which is characterized by a loss of bone mass and density due to the deterioration of the bone's microstructure, which makes the bone more fragile. As a result, it is a systemic bone condition that makes patients more likely to fracture. Interest in the function of ferroptosis in the pathophysiology of osteoporosis is developing. In this review, we go through the shape of the cell, the fundamental mechanisms of ferroptosis, the relationship between osteoclasts and osteoblasts, the association between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and the relationship between ferroptosis and postmenopausal osteoporosis. The functions of ferroptosis and osteoporosis in cellular function, signaling cascades, pharmacological inhibition, and gene silencing have been better understood thanks to recent advances in biomedical research. [ABSTRACT FROM AUTHOR]

Gingival carcinoma is a malignant neoplasm affecting the oral mucosa and is associated with significant morbidity and mortality. Allium ampeloprasum var. porrum water extracts have gotten a lot of attention because of their bioactive components, such as polyphenols, flavonoids, and alkaloids, which have a variety of pharmacological activities, including antiproliferative actions. This study aimed to evaluate the histological and molecular effects of Allium ampeloprasum (leek) water extract on the proliferation of the murine gingival cancer cell line. Histological evaluation was conducted to examine morphological changes induced by extract treatment. Molecular mechanisms underlying the observed histological changes were investigated using real-time polymerase chain reaction (PCR). Expression levels of key genes associated with cell proliferation and apoptosis were assessed. Histological findings revealed a dose-dependent decrease (100, 50, 25, 12.5, and 6.25 µg/ml) in cell density and altered cell shape in the treated cell line. Also, the percentage of inhibition for the oral mucosa cell line was high, with a significant P of 0.006, in the treated group compared to the control group. Additionally, water extract has an IC50 value of 61 g/ml. The P53 fold increment of gene expression is 0.6, which means the expression level in the experimental condition is 60% higher than the control. This study provides evidence for the potential antiproliferative activity of Allium ampeloprasum water extract on the oral mucosa cell line. The observed histological changes, coupled with the modulation of key genes involved in proliferation and apoptosis, suggest that leek water extract may have therapeutic implications in managing oral cancer. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight‐week‐old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post‐surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin‐1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non‐ischaemic limbs of HLI mice by day 7 (7.3‐ and 2.3‐fold greater than Sham, respectively, P < 0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross‐sectional area than the non‐ischaemic limb (724 ± 28 vs. 916 ± 46 μm2, P = 0.01), but the non‐ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7‐day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. Highlights: What is the central question of this study?Does hindlimb ischaemia‐induced inflammation cause acute immune, inflammatory and morphological alterations in remote non‐ischaemic skeletal muscle?What is the main finding and its importance?Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non‐ischaemic skeletal muscle; however, morphological changes did not occur in non‐ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline. [ABSTRACT FROM AUTHOR]

This article presents a case study of a patient with a rare vascular tumor called epithelioid hemangioendothelioma (EHE). The study describes the characteristics of EHE cells and discusses the challenges in diagnosing this tumor due to its variability and lack of specific markers. The article also compares EHE with other malignancies and emphasizes the importance of using vascular markers and molecular studies to confirm the diagnosis. The prognosis for EHE in the lungs or pleura is generally poor, and treatment usually involves surgery with or without chemoradiation. [Extracted from the article]

Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours. [ABSTRACT FROM AUTHOR]

Epithelial cell networks imply a packing geometry characterized by various cell shapes and distributions in terms of number of cell neighbors and areas. Despite such simple characteristics describing cell sheets, the formation of bubble‐like cells during the morphogenesis of epithelial tissues remains poorly understood. This study proposes a topological mathematical model of morphogenesis in a squamous epithelial. We introduce a new potential that takes into account not only the elasticity of cell perimeter and area but also the elasticity of their internal angles. Additionally, we incorporate an integral equation for chemical signaling, allowing us to consider chemo‐mechanical cell interactions. In addition to the listed factors, the model takes into account essential processes in real epithelial, such as cell proliferation and intercalation. The presented mathematical model has yielded novel insights into the packing of epithelial sheets. It has been found that there are two main states: one consists of cells of the same size, and the other consists of "bubble" cells. An example is provided of the possibility of accounting for chemo‐mechanical interactions in a multicellular environment. The introduction of a parameter determining the flexibility of cell shapes enables the modeling of more complex cell behaviors, such as considering change of cell phenotype. The developed mathematical model of morphogenesis of squamous epithelium allows progress in understanding the processes of formation of cell networks. The results obtained from mathematical modeling are of significant importance for understanding the mechanisms of morphogenesis and development of epithelial tissues. Additionally, the obtained results can be applied in developing methods to influence morphogenetic processes in medical applications. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans has been widely used as a model organism in developmental biology due to its invariant development. In this study, we developed a desktop software CShaperApp to segment fluorescence‐labeled images of cell membranes and analyze cellular morphologies interactively during C. elegans embryogenesis. Based on the previously proposed framework CShaper, CShaperApp empowers biologists to automatically and efficiently extract quantitative cellular morphological data with either an existing deep learning model or a fine‐tuned one adapted to their in‐house dataset. Experimental results show that it takes about 30 min to process a three‐dimensional time‐lapse (4D) dataset, which consists of 150 image stacks at a ∼1.5‐min interval and covers C. elegans embryogenesis from the 4‐cell to 350‐cell stages. The robustness of CShaperApp is also validated with the datasets from different laboratories. Furthermore, modularized implementation increases the flexibility in multi‐task applications and promotes its flexibility for future enhancements. As cell morphology over development has emerged as a focus of interest in developmental biology, CShaperApp is anticipated to pave the way for those studies by accelerating the high‐throughput generation of systems‐level quantitative data collection. The software can be freely downloaded from the website of Github (cao13jf/CShaperApp) and is executable on Windows, macOS, and Linux operating systems. [ABSTRACT FROM AUTHOR]

This study is the first to report the foliar and stem epidermal micro-morphology of 13 taxa of Indigofera L. (Fabaceae) using light (LM) and scanning electron microscopy (SEM). The micro-morphological characteristics studied here are related to the epidermal cell shape, size, frequency, anticlinal wall pattern, and stomatal complex types, size, position, frequency, and index. The study revealed 19 major normal stomatal types with eight subtypes and seven major abnormal stomatal types with 13 subtypes. The stomatal index was lower on the abaxial leaf surface than on the adaxial surface. Notably, the adaxial surface of I. hochstetteri had the highest stomatal index (27.46%), while the abaxial surface of I. oblongifolia had the lowest (9.95%). The adaxial surface of I. hochstetteri also displayed the highest average stomatal frequency (38.67), while the adaxial surface of I. spinosa had the lowest average frequency (9.37). SEM analysis revealed that most leaves had slightly sunken to sunken stomata, while stem stomata were positioned at the same level as epidermal cells in most taxa. Indigofera's foliar and stem epidermal anatomy recommends their application as baseline data coupled with other taxonomic data for the delimitation and differentiation of closely related taxa in the genus. The study provides a comprehensive description, illustrations, images, and micrographs of the stomatal types, as well as a taxonomic key for distinguishing the studied taxa of Indigofera. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most severe threats to women worldwide and holds fourth rank in lethality. It is estimated that 604, 127 cervical cancer cases have been reported in 2020 globally. With advancements in high throughput technologies and bioinformatics, several cervical candidate genes have been proposed for better therapeutic strategies. In this paper, we intend to prioritize the candidate genes that are involved in cervical cancer progression through a fractal time series-based cross-correlations approach. we apply the chaos game representation theory combining a two-dimensional multifractal detrended cross-correlations approach among the known and candidate genes involved in cervical cancer progression to prioritize the candidate genes. We obtained 16 candidate genes that showed cross-correlation with known cancer genes. Functional enrichment analysis of the candidate genes shows that they involve GO terms: biological processes, cell–cell junction assembly, cell–cell junction organization, regulation of cell shape, cortical actin cytoskeleton organization, and actomyosin structure organization. KEGG pathway analysis revealed genes' role in Rap1 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Acute myeloid leukemia, chronic myeloid leukemia, Breast cancer, Thyroid cancer, Bladder cancer, and Gastric cancer. Further, we performed survival analysis and prioritized six genes CDH2, PAIP1, BRAF, EPB41L3, OSMR, and RUNX1 as potential candidate genes for cervical cancer that has a crucial role in tumor progression. We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc. [ABSTRACT FROM AUTHOR]

Collagen-based hydrogels are commonly used in mechanobiology to mimic the extracellular matrix. A quantitative analysis of the influence of collagen concentration and properties on the structure and mechanics of the hydrogels is essential for tailored design adjustments for specific in vitro conditions. We combined focused ion beam scanning electron microscopy and rheology to provide a detailed quantitative atlas of the mechanical and nanoscale three-dimensional structural alterations that occur when manipulating different hydrogel's physicochemistry. Moreover, we study the effects of such alterations on the phenotype of breast cancer cells and their mechanical interactions with the extracellular matrix. Regardless of the microenvironment's pore size, porosity or mechanical properties, cancer cells are able to reach a stable mesenchymal-like morphology. Additionally, employing 3D traction force microscopy, a positive correlation between cellular tractions and ECM mechanics is observed up to a critical threshold, beyond which tractions plateau. This suggests that cancer cells in a stable mesenchymal state calibrate their mechanical interactions with the ECM to keep their migration and invasiveness capacities unaltered. The paper presents a thorough study on the mechanical microenvironment in breast cancer cells during their interaction with collagen based hydrogels of different compositions. The hydrogels' microstructure were obtained using state-of-the-art 3D microscopy, namely focused ion beam-scanning electron microscope (FIB-SEM). FIB-SEM was originally applied in this work to reconstruct complex fibered collagen microstructures within the nanometer range, to obtain key microarchitectural parameters. The mechanical microenvironment of cells was recovered using Traction Force Microscopy (TFM). The obtained results suggest that cells calibrate tractions such that they depend on mechanical, microstructural and physicochemical characteristics of the hydrogels, hence revealing a steric hindrance. We hypothesize that cancer cells studied in this paper tune their mechanical state to keep their migration and invasiveness capacities unaltered. [Display omitted] [ABSTRACT FROM AUTHOR]

The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an air–liquid interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist among media used for ALI-cultured human airway epithelial cells, the aim of our study was to evaluate the impact of several media (BEGM, PneumaCult, Half & Half, and Clancy) on cell type distribution using single-cell RNA sequencing and imaging. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling, and epithelial morphology. We found higher proportions of multiciliated cells in PneumaCult-ALI and Half & Half, stronger EGF signaling from basal cells in BEGM-ALI, differential expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factor ACE2, and distinct secretome transcripts depending on the media used. We also established that proliferation in PneumaCult-Ex Plus favored secretory cell fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will aid in choosing the most relevant medium according to the processes to be investigated, such as cilia, mucus biology, or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and morphology. [ABSTRACT FROM AUTHOR]

Corneal injury is one of the substantial and challenging global concerns regarding vision loss. Corneal transplantation is the gold standard for restoring vision to a blurred cornea; however, suture-related complications, corneal haziness, and graft failure have led to ongoing research to improve graft efficiency. In this study, a highly suture-able hybrid corneal scaffold composed of decellularized corneas injected with GelMa/PEGDA in situ was fabricated to preserve the structural integrity and transparency of the injured corneas. First, GelMA/PEGDA hydrogels with different ratios (3/7, 1/1, and 7/3) were evaluated in terms of microstructure, degradation rate, cytocompatibility, and equilibrium water content. GelMa/PEGDA 7/3 was chosen based on the cytocompatibility assay, which confirmed the attachment, maintenance, and proliferation of limbal stem cells with an elongated morphology. Next, the explanted rabbit cornea was decellularized successfully to preserve its extracellular components and transparency with less than 1% DNA content. Thereafter, a hybrid cornea was developed by incorporating GelMA/PEGDA hydrogel (7/3) into the decellularized rabbit cornea under ultraviolet light. This hybrid cornea showed improved sutureability and possessed appropriate transparency. In addition, ex vivo examinations of the enucleated eyeballs of rabbits showed that this hybrid cornea effectively adhered to the corneal stromal and surrounding tissues by applying GelMA/PEGDA hydrogel, which is favorable for corneal transplantations. Based on these findings, the introduced hybrid cornea could be a potential candidate for the in situ repair of deep anterior corneal defects. [ABSTRACT FROM AUTHOR]

Mesenchymal--epithelial transition (MET)-mediated endometrial decidualization is pivotal for achieving endometrial receptivity and successful pregnancy. We observed blockade of MET in the eutopic secretory endometrium of patients with endometriosis, but the underlying mechanism is unknown. In this study, real-time PCR was used to detect PRL and IGFBP1 expression, whereas western blotting was used to detect the expression of MET markers and METTL3. Phalloidin staining was used to identify changes in cell morphology. M6A levels were quantified using a colorimetric method and m6A dot blots, and functional analysis was performed using spheroid adhesion assays. We first found that increased E-cadherin expression was accompanied by decreased vimentin and Slug expression in the eutopic secretory endometrium of individuals with endometriosis. We also detected a significant increase in both the m6A level and the expression of the related methyltransferase METTL3. Finally, METTL3 expression was negatively correlated with PRL, IGFBP1, and MET markers expression. Collectively, our findings suggest that METTL3 mediates m6A modification, thereby inhibiting MET formation within the eutopic secretory endometrium of patients with endometriosis. Increased METTL3-mediated m6A modification plays a crucial role in attenuating MET formation and decidualization impairment in endometrial stromal cells, ultimately contributing to compromised endometrial receptivity in individuals with endometriosis. These insights could lead to the identification of potential therapeutic targets for improving both endometrial receptivity and pregnancy rate among individuals affected by endometriosis. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to investigate changes in tear function, meibomian glands and corneal endothelium in patients receiving systemic isotretinoin therapy. Materials and methods: This prospective study included 38 eyes from 38 patients (23 females and 15 males) treated with systemic isotretinoin (0.5–1 mg/kg/day) following the diagnosis of acne vulgaris. All patients underwent a comprehensive ophthalmologic examination at baseline, 1st month, and third month of treatment. Subjective complaints were assessed using the Ocular Surface Disease Index (OSDI). Tear functions were evaluated through non-invasive tear break up time (NIBUT) and Schirmer I test. Meibomian gland (MG) changes were examined using meibography. Corneal parameters, including endothelial cell density (ECD), coefficient of variation (CV), the number of cells with a hexagonal shape (6A), average cell area (AVG), and central corneal thickness (CCT) were assessed using non-contact specular microscopy. Results: The mean age of the patients was 19.29 ± 2.83 years. Ocular surface-related discomfort, measured with OSDI scores, significantly worsened at the third month measurements compared to the pre-treatment values (p < 0.001). In the 1st month of treatment, there was a significant decrease in NIBUT (p < 0.05). No statistically significant difference was found in the Schirmer test results at each visit. According to the 1st and third-month analysis, there was a significant increase in MG loss compared to the pre-treatment period (p < 0.001). ECD, CV, 6 A, AVG measurements at the first and third months showed a significant change compared to the pre-treatment values (p < 0.001). No significant difference was observed in the CCT measurements during the treatment. Conclusion: Systemic isotretinoin disrupted tear stability, caused MG loss, deterioration in corneal endothelium, and led to symptomatic complaints in patients. [ABSTRACT FROM AUTHOR]

The lung airways exhibit distinct features with long, wide proximal branches and short, thin distal branches, crucial for optimal respiratory function. In this study, we investigated the mechanism behind this hierarchical structure through experiments and modeling, focusing on the regulation of branch length and width during the pseudoglandular stage. To evaluate the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10), we monitored the activity of extracellular signal-regulated kinase (ERK). ERK activity exhibited an increase dependent on the curvature of the epithelial tissue, which gradually decreased with the progression of development. We then constructed a computational model that incorporates curvature-dependent growth to predict its impact on branch formation. It was demonstrated that branch length is determined by the curvature dependence of growth. Next, in exploring branch width regulation, we considered the effect of apical constriction, a mechanism we had previously proposed to be regulated by Wnt signaling. Analysis of a mathematical model representing apical constriction showed that branch width is determined by cell shape. Finally, we constructed an integrated computational model that includes curvature-dependent growth and cell shape controls, confirming their coordination in regulating branch formation. This study proposed that changes in the autonomous property of the epithelium may be responsible for the progressive branch morphology. [ABSTRACT FROM AUTHOR]

Endothelial cells, which line the lumen of blood vessels, locally sense and respond to blood flow. In response to altered blood flow dynamics during early embryonic development, these cells undergo shape changes that directly affect vessel geometry: In the dorsal aorta of zebrafish embryos, elongation of endothelial cells in the direction of flow between 48 and 72 hours post fertilization (hpf) reduces the vessel's diameter. This remodeling process requires Endoglin; excessive endothelial cell growth in the protein's absence results in vessel diameter increases. To understand how these changes in vessel geometry emerge from morphological changes of individual endothelial cells, we developed a novel mathematical approach that allows 3D reconstruction and quantification of both dorsal aorta geometry and endothelial cell surface morphology. Based on fluorescently marked endothelial cell contours, we inferred cross-sections of the dorsal aorta that accounted for dorsal flattening of the vessel. By projection of endothelial cell contours onto the estimated cross-sections and subsequent triangulation, we finally reconstructed 3D surfaces of the individual cells. By simultaneously reconstructing vessel cross-sections and cell surfaces, we found in an exploratory analysis that morphology varied between endothelial cells located in different sectors of the dorsal aorta in both wild-type and Endoglin-deficient zebrafish embryos: In wild-types, ventral endothelial cells were smaller and more elongated in flow direction than dorsal endothelial cells at both 48 hpf and 72 hpf. Although dorsal and ventral endothelial cells in Endoglin-deficient embryos had similar sizes at 48 hpf, dorsal endothelial cells were much larger at 72 hpf. In Endoglin-deficient embryos, elongation in flow direction increased between 48 hpf and 72 hpf in ventral endothelial cells but hardly changed in dorsal endothelial cells. Hereby, we provide evidence that dorsal endothelial cells contribute most to the disparate changes in dorsal aorta diameter in wild-type and Endoglin-deficient embryos between 48 hpf and 72 hpf. Author summary: Endothelial cells, which form the innermost layer of each blood vessel, sense and respond to blood flow. During early embryonic development in zebrafish, endothelial cells of the dorsal aorta elongate in the direction of blood flow and hereby decrease the vessel's diameter. To understand how these changes in vessel geometry emerge from morphological changes of individual endothelial cells, it is critical to precisely quantify both vessel geometry and cell morphology. To this end, we developed a novel mathematical approach that leverages information from fluorescently marked endothelial cell contours to reconstruct the dorsal aorta's surface in 3D. In an exploratory analysis, we applied this method to wild-type and mutant zebrafish embryos lacking functional Endoglin that is required for the physiological vessel diameter decrease. By quantifying vessel geometry and cell morphology in these embryos, we found that size and elongation in the direction of blood flow varied between endothelial cells located in different vessel sectors. Notably, we determined a subgroup of endothelial cells that contributed most to the vessel diameter increases in the absence of Endoglin. Future studies can investigate whether variability in endothelial cell behavior also contributes to the onset of human vascular malformations occurring due to a loss of Endoglin. [ABSTRACT FROM AUTHOR]

Acoustic metamaterials based on out‐of‐plane actuation can flexibly reconfigure arrayed unit cells on demand, to shape sound fields for applications such as beam formation or holography. However, implementing active reconfiguration on the millimeter‐scale is challenging, due to the lack of suitable actuation methods. Besides electronic complexity, current methods suffer from limited actuation range (sub‐millimeter), and discrete steps inhibit smooth sound modulation. Here, a novel fluid‐driven approach for continuous out‐of‐plane actuation is presented. A three dimensionally (3D)‐printed fluidic chip is integrated with an elastomeric membrane, and selective inflation of membrane sections actuates acoustic reflector unit cells according to their shape and position. The compact device enables displacements >5 mm without coupling mechanisms or external power. It is experimentally demonstrate single‐channel and multi‐channel prototypes, including an ultrasonic metasurface built for controllable acoustic focusing at five different locations. The fluidic chips are monolithically printed via digital light processing without internal support material, and the membranes are fabricated by accessible and cost‐effective spacer‐based fabrication. The methods are reproducible and eliminate complex processes (e.g., adhesion of layers) commonly associated with multi‐layered micro/milli fluidic devices. The outlined approaches and concepts in this work can be applied beyond the field of metamaterials, such as for visual displays, or tactile devices. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a prevalent joint disease affecting both humans and animals. It is characterized by articular cartilage degeneration and joint surface eburnation. Currently, no effective pharmacological treatment is available to restore the original function and structure of defective cartilage.This study explores the potential of stem cell-based therapy in treating joint diseases involving cartilage degeneration, offering a promising avenue for future research and treatment. The primary aim was to compare the characteristics and, more importantly, the chondrogenic differentiation potential of human and rat adipose-derived mesenchymal stem cells (AD-MSCs).Rat adipose tissue was collected from Sprague Dawley rats, while human adipose tissue was obtained in the form of lipoaspirate. The mesenchymal stem cells (MSCs) were then harvested using collagenase enzyme and subcultured. We meticulously evaluated and compared the cell morphology, percentage of cell viability, population doubling time, metabolic proliferation, and chondrogenic differentiation potential of MSCs harvested from both sources. Chondrogenic differentiation was induced at passage 3 using the 3D pellet culture method and assessed through histological and molecular analysis.The findings revealed that human and rat AD-MSCs were phenotypically identical, and an insignificant difference was found in cell morphology, percentage of cell viability, metabolic proliferation, and population doubling time. However, the chondrogenic differentiation potential of human AD-MSCs was evaluated as significantly higher than that of rat AD-MSCs.The current study suggests that research regarding chondrogenic differentiation of rat AD-MSCs can be effectively translated to humans. This discovery is a significant contribution to the field of regenerative medicine and has the potential to advance our understanding of stem cell-based therapy for joint diseases. [ABSTRACT FROM AUTHOR]

The ventral posterolateral nucleus (VPL), being categorized as the first‐order thalamic nucleus, is considered to be dedicated to uni‐modal somatosensory processing. Cross‐modal sensory interactions on thalamic reticular nucleus cells projecting to the VPL, on the other hand, suggest that VPL cells are subject to cross‐modal sensory influences. To test this possibility, the effects of auditory or visual stimulation on VPL cell activities were examined in anaesthetized rats, using juxta‐cellular recording and labelling techniques. Recordings were obtained from 70 VPL cells, including 65 cells responsive to cutaneous electrical stimulation of the hindpaw. Auditory or visual alone stimulation did not elicit cell activity except in three bi‐modal cells and one auditory cell. Cross‐modal alterations of somatosensory response by auditory and/or visual stimulation were recognized in 61 cells with regard to the response magnitude, latency (time and jitter) and/or burst spiking properties. Both early (onset) and late responses were either suppressed or facilitated, and de novo cell activity was also induced. Cross‐modal alterations took place depending on the temporal interval between the preceding counterpart and somatosensory stimulations, the intensity and frequency of sound. Alterations were observed mostly at short intervals (< 200 ms) and up to 800 ms intervals. Sounds of higher intensities and lower frequencies were more effective for modulation. The susceptibility to cross‐modal influences was related to cell location and/or morphology. These and previously reported similar findings in the auditory and visual thalamic nuclei suggest that cross‐modal sensory interactions pervasively take place in the first‐order sensory thalamic nuclei. [ABSTRACT FROM AUTHOR]

The response of the haloarchaeal model organism Haloferax volcanii to iron starvation was analyzed at the proteome level by data-independent acquisition mass spectrometry. Cells grown in minimal medium with normal iron levels were compared to those grown under low iron conditions, with samples being separated into membrane and cytoplasmic fractions in order to focus on import/export processes which are frequently associated with metal homeostasis. Iron starvation not only caused a severe retardation of growth but also altered the levels of many proteins. Using a comprehensive annotated spectral library and data-independent acquisition mass spectrometry (DIA-MS), we found that iron starvation resulted in significant changes to both the membrane and the soluble proteomes of Hfx. volcanii. The most affected protein is the RND family permease HVO_A0467, which is 44-fold enriched in cells grown under iron starvation. The gene HVO_A0467 can be deleted suggesting that it is not essential under standard conditions. Compared to wild type cells the deletion strain shows only slight changes in growth and cell morphologies show no differences. Molecular docking predictions indicated that HVO_A0467 may be an exporter of the siderophore schizokinen for which a potential biosynthesis cluster is encoded in the Hfx. volcanii genome. Together, these findings confirm the importance of iron for archaeal cells and suggest HVO_0467 as a siderophore exporter. [ABSTRACT FROM AUTHOR]

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI's robust and consistent performance. Integrating tissue histology with spatial transcriptomics (ST) can significantly enhance the analysis of tumor heterogeneity and the tumor microenvironment (TME). Here, the authors present METI, a computational framework to analyze cancer cells and the complex TME by integrating ST with histology imaging. [ABSTRACT FROM AUTHOR]

Introduction: Red blood cells (RBCs) undergo progressive biochemical and morphological changes during storage, collectively called storage lesion. The quality of red cell concentrates (RCCs) is typically assessed by quantifying hemolysis. An assessment of morphological changes, associated with low quality RBCs, could give an additional indication of the safety and efficacy of the concentrates. The current standard for determining morphological changes is a manual, laborious, and subjectively biased microscopic process that limits the number of cells that can be examined. When using alternative methods like flow cells, flow and shear-induced morphologies affecting especially stomatocyte morphologies must be taken into account. We already established an automated flow morphometric RBC analysis system as an alternative to manual microscopic evaluation. The goal of the present work is to obtain a robust, automated, morphology-related signal (lesion index) quantifying RBC storage lesion in a laminar flow channel under conditions similar to stasis that is not affected by shear-induced reversible morphology changes. Methods: We use a convolutional neural network (CNN) for high throughput classification of RBCs. We analyzed the morphological changes of 5 RCCs over a period of 12 weeks and classified RBC morphologies, including such that are degradation-induced and reversible. We introduce a lesion index to denote the percentage of irreversible spherical morphologies, known to reduce the post-transfusion survival of erythrocytes. We further addressed shear-induced stomatocyte morphologies in laminar flow and whether these affect CNN-based RBC classification. Results: Our flow morphometry system achieves a high-resolution classification comprising nine morphological classes with an excellent overall accuracy of 92% and F1 scores between 84% and 97%. We generate strong evidence that the morphological lesion index can predict the hemolysis level in RCCs during storage. The power of this new classification technique allowed it, for the first time, to detect and measure the lateral concentration gradient of stomatocytes in a conventional flow chamber. Importantly, we show that reversible shear rate-induced morphologies, typical for microfluidic systems, bear no influence on the lesion index. Conclusion: Flow morphometry combined with evaluation by a CNN allows to reliably assess RBC storage lesion and thus concentrate quality. Additionally, this method reduces the need for complex laboratory procedures. [ABSTRACT FROM AUTHOR]

The Drosophila corneal lens is entirely composed of chitin and other apical extracellular matrix components, and it is not known how it acquires the biconvex shape that enables it to focus light onto the retina. We show here that the zona pellucida domain-containing protein Dusky-like is essential for normal corneal lens morphogenesis. Dusky-like transiently localizes to the expanded apical surfaces of the corneal lens-secreting cells and prevents them from undergoing apical constriction and apicobasal contraction. Dusky-like also controls the arrangement of two other zona pellucida domain proteins, Dumpy and Piopio, external to the developing corneal lens. Loss of either dusky-like or dumpy delays chitin accumulation and disrupts the outer surface of the corneal lens. We find that artificially inducing apical constriction by activating myosin contraction is sufficient to similarly alter chitin deposition and corneal lens morphology. These results demonstrate the importance of cell shape in controlling the morphogenesis of overlying apical extracellular matrix structures such as the corneal lens. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. AD is a highly complex disease with different subtypes. Many elements of AD pathophysiology have been described, but if/how they interact with each other or which mechanisms are important in which patients is still unclear. Langerhans cells (LCs) are antigen‐presenting cells (APCs) in the epidermis. Depending on the context, they can act either pro‐ or anti‐inflammatory. Many different studies have investigated LCs in the context of AD and found them to be connected to all major mechanisms of AD pathophysiology. As APCs, LCs recruit other immune cells and shape the immune response, especially adaptive immunity via polarization of T cells. As sentinel cells, LCs are primary sensors of the skin microbiome and are important for the decision of immunity versus tolerance. LCs are also involved with the integrity of the skin barrier by influencing tight junctions. Finally, LCs are important cells in the neuro‐immune crosstalk in the skin. In this review, we provide an overview about the many different roles of LCs in AD. Understanding LCs might bring us closer to a more complete understanding of this highly complex disease. Potentially, modulating LCs might offer new options for targeted therapies for AD patients. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been considered as mainstream concepts and general rules driving developmental and pathological processes, particularly cancer. However, discrepancies and disputes over EMT and EMT research have also grown over time. EMT is defined as transition between two cellular states, but it is unanimously agreed by EMT researchers that (1) neither the epithelial and mesenchymal states nor their regulatory networks have been clearly defined, (2) no EMT markers or factors can represent universally epithelial and mesenchymal states, and thus (3) EMT cannot be assessed on the basis of one or a few EMT markers. In contrast to definition and proposed roles of EMT, loss of epithelial feature does not cause mesenchymal phenotype, and EMT does not contribute to embryonic mesenchyme and neural crest formation, the key developmental events from which the EMT concept was derived. EMT and MET, represented by change in cell shapes or adhesiveness, or symbolized by EMT factors, are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. Moreover, EMT and MET are consequences rather than driving factors of developmental and pathological processes. The true meaning of EMT in some developmental and pathological processes, such as fibrosis, needs re-evaluation. EMT is believed to endow malignant features, such as migration, stemness, etc., to cancer cells. However, the core property of cancer (tumorigenic) cells is neural stemness, and the core EMT factors are components of the regulatory networks of neural stemness. Thus, EMT in cancer progression is misattribution of the roles of neural stemness to the unknown mesenchymal state. Similarly, neural crest EMT is misattribution of intrinsic property of neural crest cells to the unknown mesenchymal state. Lack of basic rationale in EMT and related concepts urges re-evaluation of their significance as general rules for understanding developmental and pathological processes, and re-evaluation of their significance in scientific research. [ABSTRACT FROM AUTHOR]

Patients with epilepsy face heightened risk of post-ictal cardiorespiratory suppression and sudden unexpected death in epilepsy (SUDEP). Studies have shown that neuroinflammation, mediated by the activation of microglia and astrocytes, may be a cause or consequence of seizure disorders. Kcnj16 (Kir5.1) knockout rats (SSkcnj16-/-) are susceptible to repeated audiogenic seizures and recapitulate features of human SUDEP, including post-ictal ventilatory suppression, which worsens with repeated seizures and seizureinduced mortality. In this study, we tested the hypothesis that repeated seizures cause neuroinflammation within key brainstem regions that contribute to the control of breathing. Audiogenic seizures were elicited once/day for up to 10 days in groups of adult male SSkcnj16-/- rats, from which frozen brainstem biopsies of the pre-Bötzinger complex/nucleus ambiguus (preBötC/NA), Bötzinger complex (BötC), and raphe magnus (RMg) regions were subjected to a cytokine array. Several cytokines/chemokines, including IL-1α and IL-1ß, were increased selectively in preBötC/NA after 3 or 5 days of seizures with fewer changes in other regions tested. In additional groups of male SSkcnj16-/- rats that underwent repeated seizures, we quantified microglial (IBA-1+) cell counts and morphology, specifically within the preBötC/NA region, and showed increased microglial cell counts, area, and volume consistent with microglial activation. To further test the role of inflammation in physiological responses to seizures and seizure-related mortality, additional groups of SSkcnj16-/- rats were treated with anakinra (IL-1R antagonist), ketoprofen (nonselective COX inhibitor), or saline for 3 days before and up to 10 days of seizures (1/day), and breathing was measured before, during, and after each seizure. Remarkably, IL-1R antagonism mitigated changes in post-ictal ventilatory suppression on days 7-10 but failed to prevent seizure-related mortality, whereas ketoprofen treatment exacerbated post-ictal ventilatory suppression compared to other treatment groups but prevented seizure-related mortality. These data demonstrate neuroinflammation and microglial activation within the key brainstem region of respiratory control following repeated seizures, which may functionally but differentially contribute to the pathophysiological consequences of repeated seizures. [ABSTRACT FROM AUTHOR]

2D MXenes find applications in several technology fields. Solution processing techniques can facilitate the integration of these materials within the technological supply chain. Here, a highly concentrated (up to 1.5 g L−1) and stable dispersion of 2D Ti3C2Tx MXene flakes is produced by an environmentally friendly liquid phase exfoliation process (LPE) in dihydrolevoglucosenone (Cyrene). The flakes preserve their elemental composition after 6 months, while those exfoliated in N‐Methyl‐2‐pyrrolidone (NMP), a commonly used solvent, undergo significant oxidation. The cytotoxicity of the MXene flakes in Cyrene and in NMP is investigated by assessing the cellular viability in a human keratinocyte (HaCaT) cell line, which is a relevant model for skin applications. The data show that the MXene flakes in Cyrene induce cytotoxic effects for a dose > 1 µg cm−2, as similarly observed for the MXene flakes in NMP. Efforts are made to overcome this by collecting the MXene flakes and redispersing them in a solution of bovine serum albumin (BSA). MXene in BSA does not affect cellular viability and cell morphology, possibly due to the formation of a protective protein corona around the individual MXene flakes. These findings illustrate an environmentally friendly strategy to produce biocompatible 2D MXene for biomedical applications. [ABSTRACT FROM AUTHOR]

Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca2+, Fe3+, Cu2+ and Zn2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. Highlights: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "AAA237, an SKP2 inhibitor, suppresses glioblastoma by inducing BNIP3-dependent autophagy through the mTOR pathway" published in Cancer Cell International. The correction addresses the incorrect figures that appeared in the original article and provides the corrected figures. The corrected figures include graphs showing the effects of AAA237 on the viability, proliferation, and autophagy of glioblastoma cells. The correction also includes Western blot analysis results and other experimental data. The correction notice is authored by Yizhi Zhang, Wan Li, Yihui Yang, Sen Zhang, Hong Yang, Yue Hao, Xu Fang, Guanhua Du, Jianyou Shi, Lianqiu Wu, and Jinhua Wang. [Extracted from the article]

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS). Endothelial mesenchymal transition (EndMT) refers to the process in which endothelial cells lose endothelial cell morphology and characteristic gene expression, and acquire phenotypic characteristics and gene expression related to mesenchymal cells. Numerous studies have confirmed that EndMT is involved in the formation of atherosclerosis. Catalpol is one of the active components of Rehmannia, which has antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Studies have shown that catalpol can reduce atherosclerotic plaque induced by high sugar or fat. However, the effect of catalpol on HHCY-induced EndMT is unclear. Methods and results: In vitro HHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a cell model, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. In vivo C57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The results showed that hhcy could induce morphological transformation of endothelial cells into mesenchymal cells, increase intracellular ROS content, up-regulate α-SMA, N-cadherin, p-p65 protein expression, down-regulate VE-cadherin, CD31 protein expression, induce pathological changes of aortic root endothelium, and increase aortic endothelial ROS content. Catalpol reversed these hhcy induced outcomes. Conclusions: Catalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is the leading cause of death among women, primarily due to its potential for metastasis. As BC progresses, the extracellular matrix (ECM) produces more type-I collagen, resulting in increased stiffness. This alteration influences cellular behaviors such as migration, invasion, and metastasis. Specifically, cancer cells undergo changes in gene expression that initially promote an epithelial-to-mesenchymal transition (EMT) and subsequently, a transition from a mesenchymal to an amoeboid (MAT) migration mode. In this way, cancer cells can migrate more easily through the stiffer microenvironment. Despite their importance, understanding MATs remains challenging due to the difficulty of replicating in vitro the conditions for cell migration that are observed in vivo. Methods: To address this challenge, we developed a three-dimensional (3D) growth system that replicates the different matrix properties observed during the progression of a breast tumor. We used this model to study the migration and invasion of the Triple-Negative BC (TNBC) cell line MDA-MB-231, which is particularly subject to metastasis. Results: Our results indicate that denser collagen matrices present a reduction in porosity, collagen fiber size, and collagen fiber orientation, which are associated with the transition of cells to a rounder morphology with bleb-like protrusions. We quantified how this transition is associated with a more persistent migration, an enhanced invasion capacity, and a reduced secretion of matrix metalloproteinases. Discussion: Our findings suggest that the proposed 3D growth conditions (especially those with high collagen concentrations) mimic key features of MATs, providing a new platform to study the physiology of migratory transitions and their role in BC progression. [ABSTRACT FROM AUTHOR]

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage. [ABSTRACT FROM AUTHOR]

Background: The increasing presence of plastics in the human diet is raising public concern about the potential risks posed by nanoplastic (NP) particles, which can emerge from the degradation of plastic debris. NP ingestion poses particular risks to individuals with inflammatory bowel disease (IBD), as compromised epithelial barriers may facilitate NP translocation. Methods: In vitro, bone-marrow-derived macrophages (BMDMs) were exposed to 25 nm polymethacrylate (PMMA) or 50 nm polystyrene (PS) particles to assess morphological changes and alterations in pro- and anti-inflammatory gene expression. In vivo, mice received PMMA NP particles for 6 months before acute dextran sodium sulfate (DSS) colitis was induced to investigate NP impacts on intestinal health and inflammation. Results: PMMA and PS NP exposure in BMDMs induced morphological changes indicative of a proinflammatory phenotype characterized by enlarged amoeboid cell shapes. It also triggered an inflammatory response, indicated by increased expression of proinflammatory cytokines such as Tnfa and Il6. Unexpectedly, long-term PMMA NP administration did not affect the intestinal epithelial barrier or exacerbate acute DSS-induced colitis in mice. Colonoscopy and histological analysis revealed no NP-related changes, suggesting adverse effects on intestinal health or inflammation. Conclusion: Our findings from animal models offer some reassurance to IBD patients regarding the effects of NP ingestion. However, variations in lifestyle and dietary habits may lead to significantly higher plastic intake in certain individuals, raising concerns about potential long-term gastrointestinal effects of lifelong plastic consumption. [ABSTRACT FROM AUTHOR]

Simple Summary: Stem cell therapy for veterinary patients such as cats often requires a significant quantity of mesenchymal stromal/stem cells (MSCs), typically expanded in laboratory conditions. However, this expansion process can alter the characteristics and genetic stability of these cells. This study focused on assessing the characteristics of MSCs derived from the adipose tissue of cats (cAT-MSCs) during culture conditions. For this purpose, cell morphological features, growth behavior, and cytogenetic stability were examined in passages 2, 4, and 6. Additionally, MSCs' multipotency and surface markers were assessed. The cAT-MSCs exhibited a spindle-shaped morphology, typical of MSCs. As the cells were cultured over successive passages, a reduction in their growth rate was observed after passage 4, accompanied by abnormalities in the nuclei. cAT-MSCs showed multipotency and their surface marker expression aligned with the expected immunophenotype of MSCs. Cytogenetic studies revealed some structural abnormalities in the chromosomes of the cAT-MSCs, such as gaps, breaks, deletions, duplications, and early chromatid segregation. Nevertheless, these alterations did not show a significant increase over subsequent passages. In conclusion, cAT-MSCs decreased their proliferative capacity after passage 4, accompanied by morphological alterations and signs of structural instability. Stem cell therapy in cat patients needs a high quantity of mesenchymal stromal/stem cells (MSCs) requiring in vitro propagation under culture conditions which may potentially impact cellular characteristics and genetic stability. This study aimed to assess the in vitro characteristics and cytogenetic stability of cat adipose tissue-derived MSCs (cAT-MSCs). For this purpose, morphological features, clonogenic potential, and proliferative capacity of cAT-MSCs were assessed at passages 2 (P2), P4, and P6. Multipotency and immunophenotype were evaluated. Cytogenetic analyses were conducted up to P6. The cAT-MSCs exhibited a spindle-shaped morphology in early passages. The doubling time increased from 2.5 days at P2 to 9.4 at P4 and 10.5 at P6, accompanied by the observation of nuclear abnormalities such as cluster formation, karyorrhexis, karyolysis, and a decline in the mitotic index at P4. Cells demonstrated multipotency capacity and were CD45−, CD90+, and CD44+. Metaphase analysis at P2 and P4 revealed some indications of structural instability such as gaps, breaks, deletions, duplications, and early chromatid segregation, but these alterations did not show an increase across passages. In conclusion, cAT-MSCs decreased their proliferative capacity after P4, accompanied by morphological alterations and signs of structural instability. [ABSTRACT FROM AUTHOR]