Advanced biology最新文献

The mechanisms underlying leaf unfolding remain largely speculative and are often inferred from mathematical models. Peltate leaves, unlike typical foliage leaves, frequently emerge in a “rolled-up” state. This study investigates mechanisms related to the unrolling process in the peltate species Syngonium podophyllum by analyzing anatomical and morphological changes and quantifying forces that arise during unrolling. Leaf unrolling in S. podophyllum appears to be primarily driven by cell expansion, particularly in the upper epidermis, with cell turgor playing an important role in leaf development and unrolling. Considering leaf properties such as cell dimensions and leaf radius of curvature, this work proposes a mathematical model to further characterize the unrolling process. The model provides satisfactory predictions of curvature variations, highlighting its potential for other plant movements involving dynamic curvature changes.

Growth factors play a crucial role in regulating cellular processes such as proliferation, differentiation, and survival. Their activities are tightly modulated to ensure proper physiological functioning, with dysregulation often contributing to disease pathogenesis. Among these, the insulin-like growth factor (IGF) system that encompasses IGF-1 and IGF-receptor binding proteins is pivotal in maintaining overall cellular health by regulating growth, repair, and metabolic regulation. Capitalizing on its pro-mitogenic effects, translational studies have focused efforts on developing therapeutics based on IGF-1 for age-related muscle loss, metabolic disorders, or cardiovascular diseases. Mimetic peptide design has emerged as an innovative approach to overcoming limitations of direct IGF-1 therapy, focusing on structural optimization to enhance bioavailability, stability, and receptor specificity. Herein, the development of IGF-1 mimics and their potential clinical applications are reviewed. Their design and molecular properties, including structural considerations and mechanisms of action, are described. In vitro and in vivo approaches analyzed to provide insights into their pharmacokinetics, therapeutic efficacy, and safety profiles in animal models will be delved into. These preclinical studies shed light on the advantages of IGF-1 mimics, such as bioavailability, stability, and delivery, as well as the limitations, including potential immunogenicity.

Antimicrobial Photodynamic Therapy (aPDT) has become a potential alternative for treating multidrug-resistant bacterial skin infections, such as those caused by methicillin-resistant Staphylococcus aureus (MRSA), which are at high risk in aging individuals. One of the main components of aPDT is an agent known as a photosensitizer (PS). Some plants with high flavonoid content are reported as PS. In the genus Passiflora, flavonoids are predominant, but their photosensitizing activity has yet to be described. This study investigates the photosensitizing potential of extracts from Passiflora edulis, Passiflora alata, and Passiflora cincinnata. The butanolic fraction of P. cincinnata undergoes in vivo evaluation against intradermal MRSA infection in a senescent murine model (C57BL/6). In vitro assays determine the photoactivatable concentrations and their cytotoxicity. In vivo, MRSA-infected mice are divided into control, P. cincinnata-treated, and aPDT-treated groups. Subsequent assessments include cytokine levels, bacterial load, and cellular infiltrate in the ear. The P. cincinnata-treated group exhibits improved bacterial control, reduced leukocyte infiltration, and less weight loss. The aPDT group demonstrates a unique cytokine correlation profile, featuring more negative correlations among pro-inflammatory cytokines and interleukin-10. P. cincinnata emerges as an effective photosensitizer for aPDT in a senescent model and highlights the potential of underexplored plant-derived photosensitizers.

With the growing global threat of mosquito-borne diseases, there is an urgent need for faster, automated methods to assess disease load in mosquitoes and predict outbreaks. Current surveillance relies on manual mosquito traps and labor-intensive lab tests like polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), which are time-consuming and resource-intensive. In this study, machine learning algorithms are applied to detect dengue-infected mosquitoes based on their 3D flight patterns. Using a convolutional neural network (CNN) and cubic spline interpolation, mosquito flight trajectories are tracked, followed by classification with models including CNN, eXtreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), Random Forest, Decision Tree, Naive Bayes, Logistic Regression, Multi-Layer Perceptron (MLP), and a hybrid CNN + XGBoost model. The 5-fold cross-validation results showed that XGBoost achieved the highest mean accuracy (81.43%), while Random Forest has shown the best mean F1 Score (82.80%). Some validation folds demonstrated outstanding performance, with AdaBoost reaching 95.85% accuracy and Random Forest achieving 97.77% recall in Fold 1. The study also analyzed the impact of flight sequence size on models' performance, observing that longer sequences provided more accurate predictions. This approach offers a faster and more efficient method for assessing infection status, supporting real-time vector monitoring, and improving early disease outbreak detection.

Accurate detection of heparin-induced thrombocytopenia (HIT) antibodies is crucial for diagnosing and managing thrombotic events. Conventional immunoassays, however, often lack specificity and require confirmatory testing with fresh human platelets. To address this limitation, we optimized our previously developed cell-based enzyme-linked immunosorbent assay (ELISA) for improved HIT detection under various experimental conditions. Platelet factor 4 was immobilized on breast cancer cells (MDA-MB-231) to capture monoclonal HIT-like (KKO) and non-HIT (RTO) antibodies, which served as models to evaluate assay performance under different pH levels, ionic strengths (NaCl), and fixation methods (ethanol, paraformaldehyde, glutaraldehyde). To identify the most suitable substrate, additional cancer cell lines (HCT-116, MCF-7, HepG2) were tested under live and fixed conditions, with selected conditions validated using human HIT sera. Optimal detection tested with monoclonal antibodies was achieved using 50 mM NaCl and 4% paraformaldehyde fixation. Notably, live MDA-MB-231 and HCT-116 cells demonstrated superior sensitivity and specificity compared to fixed cells. Furthermore, these cell lines enable the efficient detection of HIT antibodies using flow cytometry, a robust and platelet-free diagnostic method. Our findings establish live MDA-MB-231 and HCT-116 cells as highly promising platforms for clinical applications in HIT antibody detection.

The S-phase kinase-associated protein 1 (Skp1)-Cullin-F-box protein E3 ligase adaptor F-box-only protein 31 (FBXO31) regulates genomic stability and cell signaling in normal, genotoxic, and tumor cells by recognizing and ubiquitinating multiple downstream substrates. The stability and role of FBXO31 may be regulated by specific residual modification. In this study, five FBXO31 phosphorylation sites are identified in HEK293T cells using biochemical and biological techniques. Liquid chromatography–tandem mass spectrometry identifies phosphorylated residues, including threonine-28 and -37 and serine-33, -400, and -523. The PyMOL crystal structure reveals the location of these residues on FBXO31 and assesses whether they interact with the reported kinases. Western blotting and fluorescence-activated cell sorting demonstrate that the phosphorylation of Thr-37 and Ser-523 contributes to FBXO31 protein stabilization, which is further confirmed by cycloheximide experiments. The regulatory roles of Thr-37 and Ser-523 in FBXO31 stability are associated with variations in phosphorylation levels and degradation pathways. These results demonstrate that phosphorylation regulates FBXO31 turnover, and phosphorylation at Thr-37 or Ser-523 may help identify upstream kinases and enhance the understanding of the physiological role of FBXO31.

Mesenchymal stem cells (MSCs) migrate to injured tissues, aiding tissue repair, remodeling, and wound healing. As tumors are often considered to have traits of “injured tissues,” MSCs are recruited to tumor microenvironments where they can have pro- and antitumorigenic influences. This study assesses whether human mesenchymal stem cells (hMSCs) of shared ancestry exhibit similar tumorigenic properties. Bone marrow-derived (hBM-MSCs) and umbilical cord-derived (hUC-MSCs) MSCs embedded in collagen are cultured in conditioned media from lung adenocarcinoma (A549) cells to mimic the extracellular matrix and soluble cues of the cancer microenvironment. Cell viability, proliferation, and immunofluorescence analyses evaluate MSC behavior under these conditions. Further, A549 cells are exposed to conditioned media from cancer-stimulated MSCs to simulate indirect co-culture, and their response is assessed through viability, immunofluorescence, and flow cytometric analysis. Results show increased viability and proliferation of hBM-MSCs, morphological changes, and elevated alpha-smooth muscle actin expression, suggesting a transition toward cancer-associated fibroblasts. In contrast, hUC-MSCs display reduced viability and no morphological alterations. Conditioned media from cancer-exposed hUC-MSCs induce apoptosis in A549 cells, whereas hBM-MSCs support A549 growth. These findings demonstrate that, despite their common origin, hUC-MSCs and hBM-MSCs exhibit opposing responses to tumor cues and influence lung cancer cell behavior differently.

Label-free optical stimulation of brain cells with infrared (IR) light provides a powerful tool for spatially targeted neuromodulation. However, lingering questions about the off-target effects of IR stimulation on non-neuronal cells remain sparsely explored. It is shown that rat astroglial cultures are independently sensitive to single pulses of infrared light, evoking calcium signaling and osmoregulatory phenomena in vitro. Recent studies highlight that astrocytes respond differently to electromagnetic and laser stimulation, recruiting different pathways. The impact of three different IR stimulation time courses on astrocyte calcium and water transport dynamics is explored with widefield fluorescence microscopy and pharmacology to fill this gap. Results show that different stimulation methods can evoke astrocyte calcium responses, resulting from distinct biomolecular signaling processes. Notably, swelling and shrinkage are also differently evoked by short-term and long-term stimulation pulses. It is shown that specific IR stimulation can drive selective water and calcium dynamics in astrocytes. The work uniquely reports label-free optical modulation techniques to drive astroglial homeostatic machinery, a crucial process in healthy brain function that lacks tools for spatially precise modulation. More broadly, the results demonstrate the need to consider off-target effects with neuromodulation strategies and how to use such effects to study brain physiology.

Spheroid Cell Aggregation

In article number 2500092, Kenjiro Takemura and co-workers demonstrate that ultrasound-based, enzyme-free cell detachment accelerates spheroid formation by preserving surface proteins, reducing variability, and enhancing cell aggregation. Comparable engraftment and improved spatial organization in co-cultured spheroids were observed. These findings suggest ultrasound detachment as a robust alternative for efficient, high-quality spheroid production in tissue engineering and related biomedical applications.

Sarcopenia is a specific disease that commonly occurs in the elderly and patients with consumptive diseases. Sarcopenia can cause a severe decline in strength and movement, and even lead to prolonged bed rest. Nutritional support is an emerging approach to mitigate sarcopenia and is currently the gold standard for clinical management of sarcopenia. However, complex nutritional composition may affect the effect of treatment. Herein, the pathogenesis of sarcopenia is first introduced. Then, the diagnostic methods of sarcopenia are described in detail, including grip strength, chair stand test, dual-energy X-ray Absorptiometry, bioelectrical impedance analysis, gait speed, balance tests, and biomarkers. Then, the latest progress of the nutritional support (including protein quantity and quality, bioactive peptides, amino acids and their metabolites, antioxidant/ anti-inflammatory nutrients, vitamins and minerals, microbiome-targeted interventions, metabolite-derived molecules, and Chinese herbal medicine) on the mitigation of sarcopenia is elaborated. This review may contribute to the understanding of the mechanism and importance of diagnosis and nutritional support in alleviating sarcopenia, so as to promote the development of sarcopenia treatment.