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The cytoskeleton, a dynamic network of structural proteins within cells, is essential for cellular deformation and responds to external mechanical cues. Here, based on the structure of the cytoskeleton, combined with the biochemical reactions of the activator RhoA and the inhibitor F-actin, we develop a novel mechanochemical cytoskeleton model to investigate the mechanical behavior of cells. Interestingly, we find that active stress fibers exhibit diverse dynamical modes at specific inhibitor concentration thresholds. The existence of concentration differences and sustained mechanochemical feedback in activators and inhibitors trigger a global oscillation of isolated cells. In addition, under uniaxial and biaxial stretches, activators and inhibitors preferentially diffuse toward the more significantly deformed cytoskeletal elements, and their dynamic interactions regulate the cell to align with the main stretching direction. Our findings, consistent with many experimental results, provide fundamental insights into cytoskeletal remodeling and cellular mechanosensing mechanisms. [ABSTRACT FROM AUTHOR]

IntroductionPneumonia is a common infection in the intensive care unit (ICU), and gram-negative bacilli are the most common bacterial cause. The purpose of the study was to investigate the risk factors for 30-day mortality in patients with gram-negative bacillary pneumonia in the ICU, construct a predictive model, and stratify patients based on risk to assess their short-term survival.MethodsPatients admitted to the ICU with gram-negative bacillary pneumonia at Fujian Medical University Affiliated First Hospital between January 2018 and September 2020 were selected. Patients were divided into deceased and survivor groups based on whether death occurred within 30 days. Multifactorial logistic regression analysis was used to identify independent risk factors for 30-day mortality in these patients, and a predictive nomogram model was constructed based on these factors. Patients were categorized into low-, medium-, and high-risk groups according to the model's predicted probability, and Kaplan-Meier survival curves were plotted to assess short-term survival.ResultsThe study included 305 patients. Lactic acid (odds ratio [OR], 1.524, 95% CI: 1.057-2.197), tracheal intubation (OR: 4.202, 95% CI: 1.092-16.169), and acute kidney injury (OR:4.776, 95% CI: 1.632-13.978) were identified as independent risk factors for 30-day mortality. A nomogram prediction model was established based on these three factors. Internal validation of the model showed a Hosmer-Lemeshow test result of X2=5.770, P=0.834, and an area under the ROC curve of 0.791 (95% CI: 0.688-0.893). Bootstrap resampling of the original data 1000 times yielded a C-index of 0.791, and a decision curve analysis indicated a high net benefit when the threshold probability was between 15%-90%. The survival time for low-, medium-, and high-risk patients was 30 (30, 30), 30 (16.5, 30), and 17 (11, 27) days, respectively, which were significantly different.ConclusionLactic acid, tracheal intubation, and acute kidney injury were independent risk factors for 30-day mortality in patients in the ICU with gram-negative bacillary pneumonia. The predictive model constructed based on these factors showed good predictive performance and helped assess short-term survival, facilitating early intervention and treatment.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub‐niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM. Our observations suggest that HSCs can respond to the mechanical heterogeneity of the BM microenvironment, exhibiting diversity in cell mechanics, haematopoietic pool maintenance and differentiated lineages. Hydrogels with higher stiffness promote the preservation of long‐term repopulating HSCs (LT‐HSCs), while those with lower stiffness support multi‐potent progenitors (MPPs) viability in vitro. Furthermore, we established a comprehensive transcriptional profile of haematopoietic subpopulations to reflect the multipotency of haematopoietic stem and progenitor cells (HSPCs) that are modulated by niche‐like stiffness. Our findings demonstrate that HSPCs exhibit completely distinct downstream differentiated preferences within hydrogel systems of varying stiffness. This highlights the crucial role of tissue‐specific mechanical properties in HSC lineage decisions, which may provide innovative solutions to clinical challenges. [ABSTRACT FROM AUTHOR]