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Animal cells in tissues are supported by biopolymer matrices, which typically exhibit highly nonlinear mechanical properties. While the linear elasticity of the matrix can significantly impact cell mechanics and functionality, it remains largely unknown how cells, in turn, affect the nonlinear mechanics of their surrounding matrix. Here, we show that living contractile cells are able to generate a massive stiffness gradient in three distinct 3D extracellular matrix model systems: collagen, fibrin, and Matrigel. We decipher this remarkable behavior by introducing nonlinear stress inference microscopy (NSIM), a technique to infer stress fields in a 3D matrix from nonlinear microrheology measurements with optical tweezers. Using NSIM and simulations, we reveal large long-ranged cell-generated stresses capable of buckling filaments in the matrix. These stresses give rise to the large spatial extent of the observed cell-induced matrix stiffness gradient, which can provide a mechanism for mechanical communication between cells.

We present a new mechanism--discovered using molecular dynamics simulations--that leads to complete healing of nanocracks. This mechanism relies on the generation of crystal defects known as disclinations by migrating grain boundaries. Crack healing by disclinations does not require any compressive loads applied normal to the crack faces and even occurs under monotonic tensile loading. By closing small cracks and suppressing the propagation of others, this mechanism may provide a novel way of mitigating internal damage that influences ductility in nanocrystalline metals.

BackgroundRenal impairment (RI) is associated with worse outcomes in the treatment of intravenous thrombolysis and emergent endovascular treatment (EVT) in anterior circulation stroke. The objective of this study was to investigate the association of RI with short-term and long-term outcomes in patients with vertebrobasilar artery occlusions (VBAO) who received EVT.MethodsConsecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. Multivariate regression analyses were used to evaluate the association of RI with mortality and symptomatic intracranial hemorrhage (sICH) during the hospital stay, and also mortality, favorable functional outcome (modified Rankin Scale (mRS) score of 0–3), and functional improvement (shift in mRS score) at 3 months and 1 year follow-up. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsAfter adjustment for potential confounders, RI was independently associated with sICH (OR 3.30, 95% CI 1.55 to 7.18), as well as mortality (OR 2.54, 95% CI 1.47 to 4.38; OR 3.07, 95% CI 1.72 to 8.08), favorable functional outcome (OR 0.33, 95% CI 0.17 to 0.66; OR 0.25, 95% CI 0.12 to 0.51), and functional improvement (OR 0.45, 95% CI 0.28 to 0.74; OR 0.35, 95% CI 0.21 to 0.60) at 3 months and 1 year follow-up, respectively, but RI was not associated with in-hospital mortality. Additionally, there was no significant association between RI and recurrent stroke within 1 year.ConclusionsOur findings suggest that RI is associated with a higher risk of sICH in hospital and a decrease in survival, favorable functional outcome, and functional improvement at 90 days and 1 year follow-up.Trial registration numberURL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

MicroRNAs are known to play essential role in the gene expression regulation in cancer. In our research, next-generation sequencing technology was applied to explore the abnormal miRNA expression of oral squamous cell carcinoma (OSCC) in Chinese hamster. A total of 3 novel miRNAs (Novel-117, Novel-118, and Novel-135) and 11 known miRNAs (crg-miR-130b-3p, crg-miR-142-5p, crg-miR-21-3p, crg-miR-21-5p, crg-miR-542-3p, crg-miR-486-3p, crg-miR-499-5p, crg-miR-504, crg-miR-34c-5p, crg-miR-34b-5p and crg-miR-34c-3p) were identified. We conducted functional analysis, finding that 340 biological processes, 47 cell components, 46 molecular functions were associated with OSCC. Meanwhile the gene expression of Caspase-9, Caspase-3, Bax, and Bcl-2 were determined by qRT-PCR and the protein expression of PTEN and p-AKT by immunohistochemistry. Our research proposed further insights to the profiles of these miRNAs and provided a basis for investigating the regulatory mechanisms involved in oral cancer research.