Abstract Background Interfacial heterogeneity is widely explored to reveal molecular mechanisms of force-mediated pathways due to biased tension. However, the influence of cell density,, curvature, and interfacial heterogeneity on underlying pathways of mechanotransduction is obscure. Methods Polydimethylsiloxane (PDMS)-based stencils were micropatterned to prepare the micropores for cell culture. The colonies of human mesenchymal stem cells (hMSCs) were formed by controlling cell seeding density to investigate the influences of cell density, curvature and heterogeneity on mechanotransduction. Immunofluorescent staining of integrin, vinculin, and talin-1 was conducted to evaluate adhesion-related expression levels. Then, immunofluorescent staining of actin, actinin, and myosin was performed to detect cytoskeleton distribution, especially at the periphery. Nuclear force-sensing mechanotransduction was explained by yes-associated protein (YAP) and laminA/C analysis. Results The micropatterned colony of hMSCs demonstrated the coincident characters with engineered micropores of microstencils. The cell colony obviously developed the heterogeneous morphogenesis. Heterogeneous focal adhesion guided the development of actin, actinin, and myosin together to regulate cellular contractility and movement by integrin, vinculin, and talin-1. Cytoskeletal staining showed that actin, actinin, and myosin fibers were reorganized at the periphery of microstencils. YAP nuclear translocation and laminA/C nuclear remodeling were enhanced at the periphery by the regulation of heterogeneous focal adhesion (FA) and cytoskeleton arrangement. Conclusions The characters of the engineered clustering colony showed similar results with prepared microstencils, and colony curvature was also well adjusted to establish heterogeneous balance at the periphery of cell colony. The mechanism of curvature, spreading, and elongation was also investigated to disclose the compliance of FA and cytoskeleton along with curvature microarrays for increased nuclear force-sensing mechanotransduction. The results may provide helpful information for understanding interfacial heterogeneity and nuclear mechanotransduction of stem cells.

• Book : 30(1)
• Pub. Date : 2025
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Abstract Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells. We used multiplex, single-cell imaging to build a proteomic map of senescence induction in human epithelial cells induced to senescence over the course of 31 days. We map how the expression of SASP proteins increases alongside other known senescence markers such as p53, p21, and p16INK4a. The aggregated population of cells responded to etoposide with an accumulation of stress response factors over the first 11 days, followed by a plateau in most proteins. At the single-cell level, however, we identified two distinct senescence cell populations, one defined primarily by larger nuclear area and the second by higher protein concentrations. Trajectory inference suggested that cells took one of two discrete molecular paths from unperturbed healthy cells, through a common transitional subpopulation, and ending at the discrete terminal senescence phenotypes. Our results underscore the importance of using single-cell proteomics to identify the mechanistic pathways governing the transition from senescence induction to a mature state of senescence characterized by the SASP.

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• Pub. Date : 2025
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We present a novel cosmological framework where cosmic expansion arises from the gravitational collapse and bounce of a uniform, spherically symmetric cloud of mass \( m \) with an initial comoving radius \( \chi_* \). Extending Lemaître's 1933 'atom universe,' this model incorporates a perfect fluid with an evolving equation of state \( P = P(\rho) \), transitioning from pressureless dust \( P = 0 \) to a ground state with fixed energy density (\( \rho_G \)) as required by the quantum exclusion principle. This results in negative pressure (\( P_G = -\rho_G \)) and a gravitational bounce at the gravitational radius \( R_B \), associated with \( \rho_G \) (\( R_B \simeq 24 \) km for nuclear saturation density). The bounce triggers an expansion phase, with \( P(\rho) \) serving as the inflationary potential. This framework explains the cosmic cutoff scale (\( \chi_* \simeq 15.9 \) Gpc) which addresses key observed CMB anomalies. The bounce is trapped within the initial gravitational radius \( r_S = 2Gm \), which acts like a \( \Lambda \) term with \( r_S=\sqrt{3 /\Lambda} \simeq 5.1 \) Gpc. This approach provides a unified explanation of inflation and its observational signatures, offering new insights into cosmic expansion and the quantum origins of structures.

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• Pub. Date : 2025
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Wild emmer wheat (Triticum turgidum ssp. dicoccoides) is the ancestral species of cultivated tetraploid wheat with BBAA genomes. Because of its full interfertility with domesticated emmer wheat, this wild species can serve as one of the most important genetic resources to improve durum and bread wheat. To clarify the magnitude of genetic diversity between and within populations of Turkish wild emmer wheat, 169 genotypes of ssp. dicoccoides selected from the 38 populations collected from the three sub-regions (East-1, West-1, and West-2) of the Southeast Anatolia Region of Turkey were molecularly and morphologically characterized. The populations showed significant variation in plant height, heading date, flag leaf area, spike length and number, spikelet, peduncle, lemma, palea, glume and anther lengths, glume hull thickness, anther width, and days to maturity. According to the results of nuclear-SSR analysis, the populations collected from the sub-regions East-1 and West-2 were the most genetically distant (0.539), while the populations collected from the sub-regions West-1 and West-2 were the most genetically similar (0.788) populations. According to the results of AMOVA, there was 84% similarity within the populations studied, while the variation between the populations of the three sub-regions was 16%. In the dendrogram obtained by using nuclear-SSR data, the populations formed two main groups. The populations from the sub-region East-1 were in the first group, and the populations from the sub-regions West-1 and West-2 were in the second group. From the dendrogram, it appears that the populations from the sub-region East-1 were genetically distant from the populations from the sub-regions West-1 and West-2. The results highlight the potential diversity in Southeast Anatolia for wild emmer discovery and utilization.

• Book : 15(2)
• Pub. Date : 2025
• Page : pp.203-203
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• Pub. Date : 2025
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Vitreoretinal lymphoma (VRL) remains a diagnostic challenge due to its scarce prevalence, and delayed diagnosis usually results in blindness and even fatal outcomes. Herein, an artificial intelligence (AI) system is developed to identify VRL among 16 retinal diseases and conditions on optical coherence tomography (OCT) images with the cross‐subject meta‐transfer learning (CS‐MTL) algorithm. Extensive experiments of few‐shot VRL recognition tasks prove the robustness of our model on 1‐, 3‐, and 5‐shot scenarios, achieving an F1 score of 0.8697 to 0.9367. The superiority of the model is shown with a higher F1 score (0.9310) compared with other state‐of‐the‐art algorithms (0.5487–0.9018) and three doctors whose clinical experiences range between 3 to 10 years without the help of the CS‐MTL (0.7773–0.8949). AI assistance significantly improves the F1 scores of doctors by 6.16–14.46% (p < 0.001). Moreover, the F1 scores of AI‐assisted senior doctor and retinal specialist (0.9414 and 0.9500), but not the junior doctor (0.8897), exceed that of the CS‐MTL (0.9310). This study presents a promising approach for aiding in the diagnosis of VRL on retinal OCT images and may provide a novel insight into the collaboration of doctors with AI techniques, resulting in reducing the risk of diagnostic delays of rare diseases.

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• Pub. Date : 2025
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• Pub. Date : 2025
• Page : pp.101728-101728
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Precise control of individual particles is crucial for biomedical diagnostics, i.e., single-cell analysis and drug delivery. Acoustic tweezers have shown promise as a precise method for capturing microscale objects, but the spatial selectivity remains challenging to achieve with traditional electroacoustic transducers. An alternative to traditional ultrasound generation is to use photoacoustic conversion from laser pulses, allowing easy customization of acoustic field using optical light patterns, but this approach suffers from low efficiency of photoacoustic conversion. Here, we propose a field-hybridization technique to combine a hologram-generated photoacoustic field with a high-power featureless electroacoustic field. Theoretical and experimental validation show that while the force remains limited to the low pN range, the hybridization amplifies the photoacoustic radiation force by a factor of 80. By adjusting phase difference between electroacoustic and photoacoustic sources, the direction of particle motion can be reversed. The maximum trapping force is reached within 40 μm from the laser spot, which suggests that the method could enable highly precise and selective manipulation. Published by the American Physical Society 2025

• Book : 23(1)
• Pub. Date : 2025
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AbstractCytoplasmic TDP43 mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that Nemo-like kinase (NLK)—a proline-directed serine/threonine kinase—promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels are selectively elevated in neurons exhibiting TDP43 mislocalization in ALS patient tissues, while genetic reduction ofNLKreduces toxicity in human neuron models of ALS. Our findings suggest that NLK is a promising therapeutic target for neurodegenerative diseases.

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• Pub. Date : 2025
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• Pub. Date : 2025
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