Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell's mechanical microenvironment changes substantially over the course of development, ...beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed "mechanical memory" in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.
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•EBSD misorentation analysis is developed to depict localized creep-fatigue damage.•GND density map is explored to understand creep-fatigue failure physical ...mechanism.•Semi-quantitative study of EBSD parameters supports microscopic damage degree.
A large number of strain-controlled creep-fatigue tests under wide loading waveforms are conducted at 650 ℃ in nickel-based forged GH4169 superalloy. Comprehensive characterizations, including scanning electron microscope (SEM), electron backscatter diffraction (EBSD) and transmission electron microscope (TEM), are observed from the post-test examinations. Particular focus is brought to the physical understanding of damage mechanisms under wide creep-fatigue loading conditions using EBSD analysis. The representative misorientation parameters are calculated for constructing diffraction-based misorientation mapping. Semi-quantitative analysis of longitudinal EBSD observations is conducted to prove that strain ratio has little influence on creep-fatigue damage degrees, while dwell time causes noticeable changes to damage progressions. In particular for geometrically necessary dislocation (GND) map explored in this work, more fundamental information based on failure physics is obtained to analyze the creep-fatigue crack initiation mechanism.
The rational design of artificial solid‐state nanopores is of great importance in the discovery of intriguing ion transport phenomena. 2D metal–organicframework (2D MOF) nanosheets with single ...crystallinity, aligned nanochannels, ultrathin thickness, and diverse functionalities are highly potential solid‐state nanopores. An electrophoretic method is developed to successfully fabricate MOF nanopores supported by SiNx substrate, which is confirmed by high‐resolution transmission electron microscopy. A giant gap around 4 V together with ionic current rectification is discovered in nonlinear voltage‐activated current‐voltage curves, revealing the synergy of the hydrophobic effect and charge effect in MOF nanopores. The charge effect embodies the different contribution current which results from the enrichment and depletion of ions in MOF nanopores by COMSOL simulation. Moreover, 2D MOF nanosheets with different surface charges, hydrophobicity, and pore sizes demonstrate the universality of nanopore fabrication and further confirm the synergistic mechanism. The nonlinear ion transport in the ultrathin MOF nanosheets will provide an opportunity to explore further applications in solid‐state nanopores.
Nonlinear ion transport through the single crystalline two‐dimensional ultrathin metal–organic framework nanosheets is discovered along with a giant gap of low conductance state as well as the rectification inversion. The synergetic mechanism is revealed by the combination of the regulation of physical and chemical parameters and simulations.
Neutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of ...neutrophils in human gastric cancer (GC) are presently unknown.
Flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test. Neutrophils and T cells were isolated, stimulated and/or cultured for in vitro and in vivo regulation and function assays.
Patients with GC showed a significantly higher neutrophil infiltration in tumours. These tumour-infiltrating neutrophils showed an activated CD54
phenotype and expressed high level immunosuppressive molecule programmed death-ligand 1 (PD-L1). Neutrophils activated by tumours prolonged their lifespan and strongly expressed PD-L1 proteins with similar phenotype to their status in GC, and significant correlations were found between the levels of PD-L1 and CD54 on tumour-infiltrating neutrophils. Moreover, these PD-L1
neutrophils in tumours were associated with disease progression and reduced GC patient survival. Tumour-derived GM-CSF activated neutrophils and induced neutrophil PD-L1 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signalling pathway. The activated PD-L1
neutrophils effectively suppressed normal T-cell immunity in vitro and contributed to the growth and progression of human GC in vivo; the effect could be reversed by blocking PD-L1 on these neutrophils.
Our results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.
The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of ...NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.
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Although correlated with the severity of disease course, the impact of neutrophil‐to‐lymphocyte ratio (NLR) on survival and tumor characteristics in cancer patients remains unclear. In the meta‐analysis presented here, elevated pre‐treatment NLR was found to predict poor overall survival in patients with colorectal cancer. NLR was also associated with unfavorable biologic behavior in colorectal cancer. The findings suggest that NLR, as an inexpensive and widely available index, should be routinely monitored in colorectal cancer patients.
Early detection of cervical lesions, accurate diagnosis of cervical lesions, and timely and effective therapy can effectively avoid the occurrence of cervical cancer or improve the survival rate of ...patients. In this paper, the spectra of tissue sections of cervical inflammation (
n
= 60), CIN (cervical intraepithelial neoplasia) I (
n
= 30), CIN II (
n
= 30), CIN III (
n
= 30), cervical squamous cell carcinoma (
n
= 30), and cervical adenocarcinoma (
n
= 30) were collected by a confocal Raman micro-spectrometer (LabRAM HR Evolution, Horiba France SAS, Villeneuve d’Ascq, France). The Raman spectra of six kinds of cervical tissues were analyzed, the dominant Raman peaks of different kinds of tissues were summarized, and the differences in chemical composition between the six tissue samples were compared. An independent sample
t
test (
p
≤ 0.05) was used to analyze the difference of average relative intensity of Raman spectra of six types of cervical tissues. The difference of relative intensity of Raman spectra of six kinds of tissues can reflect the difference of biochemical components in six kinds of tissues and the characteristic of biochemical components in different kinds of tissues. The classification models of cervical inflammation, CIN I, CIN II, CIN III, cervical squamous cell carcinoma, and cervical adenocarcinoma were established by using a support vector machine (SVM) algorithm. Six types of cervical tissues were classified and identified with an overall diagnostic accuracy of 85.7%. This study laid a foundation for the application of Raman spectroscopy in the clinical diagnosis of cervical precancerous lesions and cervical cancer.
A visual detection method for malachite green (MG) in food was established based on 'double-response-OFF' ratiometric fluorescent paper-based sensor. Biomass carbon quantum dots (BCQDs) using broad ...bean shell, and Ti3C2MXene quantum (MQDs) dots modified by ethylenediamine were synthesized by solvothermal method. The MG and two kinds of quantum dots could undergo static quenching, and the fluorescence color of two kinds of quantum dots gradually changed from red to blue, eventually the fluorescence was quenched, and the pattern had a two-stage linear relationship using fluorescent spectrofluorometer in the range of 0.1-140.0μM and the detection limit of 0.07μM. On this basis, a BCQDs/MQDs ratiometric fluorescence paper-based sensor was constructed and applied to fish sample. Through mobile phone software-Color recognizer, RGB values of fluorescent paper-based sensor at various concentrations of MG were extracted. The results showed that MG concentration was linearly correlated withR' value of RGB in the range of 20.0-140.0μM with 16.5μM detection limit. The method had been applied to the determination of canned fish and fresh basa fish samples, and the recovery rates were 97.33%-108.93% and 96.04%-117.97%, respectively. It proved that the ratiometric fluorescent paper-based sensor could be used for the rapid visual quantitative detecting MG in real samples.
•Macro-to-micro FEM with dual-scale modelling approach for holed structures.•Accurate crack initiation life prediction abilities within ±2.0 error band.•Simulated crack initiation sites in ...consistency with microstructure observations.•Potential values for the dual-scale approach in scientific and engineering aspects.
In this paper, a dual-scale modelling approach is developed to investigate creep-fatigue behavior and predict crack initiation life for holed structures under multi-axial stress state. The macro-scale simulation supplies local deformation histories to the dual-scale simulation as boundary conditions. In the dual-scale simulation process, the micro-mechanical behavior and damage evolution are described by using crystal plasticity. In order to validate the dual-scale simulation procedures, a series of creep-fatigue tests as well as the post-test characterizations were carried out for nickel-based Inconel 718 at 650 ℃. The detailed results of macro- and micro-scale simulations are presented in terms of stress–strain behavior, damage evolution and life prediction. Regarding the macro-scale simulations as the benchmark, it may provide an assistant support and precognition for the micro-scale damage calculation at higher cycles. The predicted cycle numbers to crack initiation are in agreement with the experimental ones. More advantages are manifested in the potential scientific and engineering significance for the dual-scale modelling approach.
Guided by the UPLC-ESIMS profile, seven previously undescribed halogenated dihydroisocoumarins, palmaerones A-G, along with eleven known dihydroisocoumarins, were isolated from Lachnum palmae, an ...endophytic fungus from Przewalskia tangutica by exposure to a histone deacetylase inhibitor SAHA. Structures of the isolates were elucidated by analysis of their NMR, MS and optical rotation values. The antimicrobial, anti-inflammatory and cytotoxic activities of palmaerones A-G were evaluated. Palmaerones A-G showed antimicrobial activities against the strains (C. neoformans, Penicillium sp., C. albicans, B. subtilis and S. aureus), and palmaerone E exhibited potential antimicrobial activities against all the test strains with the MIC value in the range of 10–55 μg/mL. Palmaerones A and E exhibited moderate inhibitory effects on NO production in LPS-induced RAW 264.7 cells, with the IC50 values of 26.3 and 38.7 μM, respectively and no obvious toxicities were observed at 50 μM. Palmaerone E showed weak cytotoxicity against HepG2 with the IC50 value of 42.8 μM. This work provides an effective strategy for expanding natural product resource.
Seven previously undescribed halogenated dihydroisocoumarins were isolated from Lachnum palmae by exposure to SAHA. The antimicrobial, anti-inflammatory and cytotoxic activities of the previously undescribed compounds were evaluated. Display omitted
•Seven previously undescribed dihydroisocoumarins were isolated from Lachnum palmae.•Their structures were elucidated by extensive spectroscopic analysis.•Palmaerone E exhibited potential antimicrobial activities against all the test strains.•Palmaerones A and E exhibited moderate NO inhibitory activities in RAW 264.7 cells.•Palmaerone E showed weak cytotoxicity against HepG2.
•Filling the gaps of fatigue tests under non-proportional multiaxial random loading.•Elucidating the cyclic behaviors under different non-proportion factors.•Revealing the deformation mechanisms ...under various random loadings.•Proposing an effective life evaluation method for random loading conditions.
Fatigue tests on AISI304 stainless steel under non-proportional multiaxial random loading conditions were conducted with uniform hollow specimens at room temperature. The results revealed initial hardening and subsequent cyclic softening under uniaxial loadings and additional hardening under non-proportional multiaxial loadings. This shift from softening to additional hardening significantly reduced the failure life. Fractographic analysis and Electron Backscatter Diffraction (EBSD) observations identified planar slip as the dominant deformation mechanism under uniaxial loading. Multiple slip system activations, strong slip interactions, and martensitic transformation were key factors influencing changes in cyclic deformation behavior under non-proportional loadings. A novel life evaluation method based on the Itoh–Sakane (IS) method was established, demonstrating accurate evaluations for both uniaxial and non-proportional multiaxial fatigue life under random loading conditions.
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