Integrated Mathematical and Experimental Study of Cell Migration and Shape

Cell migration plays an essential role in many of physiological and pathological processes, including morphogenesis, inflammation, wound healing, and tumor metastasis. It is a complex process that involves multi-scale interactions between the cell and the extracellular matrix (ECM). Cells migrate through stromal ECM with native and cell-derived curvature at micron-meter scale are context-specific. How does the curvature of ECM mechanically change cell morphology and motility? Can the diverse migration behaviors from genetically identical cells be predictively using cell migrating data? We address these questions using an integrated computational and experimental approach: we developed three-dimensional biomechanical cell model and measured and analyzed a large number of cell migration images over time. Our findings suggest that 1. substrate curvature determines cell shape through contact and regulating protrusion dynamics; 2. effective cell migration is characterized with long cellular persistence time, low speed variation, spatial-temporally coordinated protrusion and contraction; 3. the cell shape variation space is low dimensional; and 4. migration behavior can be determined by a single image projected in the low dimensional cell shape variation space

Coordinates in low-dimensional cell shape-space discriminate migration dynamics from single static cell images

Cell shape has long been used to discern cell phenotypes and states, but the underlying premise has not been quantitatively tested. Here, we show that a single cell image can be used to discriminate its migration behavior by analyzing a large number of cell migration data in vitro. We analyzed a large number of two-dimensional cell migration images over time and found that the cell shape variation space has only six dimensions, and migration behavior can be determined by the coordinates of a single cell image in this 6-dimensional shape-space. We further show that this is possible because persistent cell migration is characterized by spatial-temporally coordinated protrusion and contraction, and a distribution signature in the shape-space. Our findings provide a quantitative underpinning for using cell morphology to differentiate cell dynamical behavior.Comment: 29 pages, 9 figure

A tumor microenvironment-responsive micelle co-delivered radiosensitizer Dbait and doxorubicin for the collaborative chemo-radiotherapy of glioblastoma

Glioblastoma is rather recalcitrant to existing therapies and effective interventions are needed. Here we report a novel microenvironment-responsive micellar system (ch-K5(s-s)R8-An) for the co-delivery of the radiosensitizer Dbait and the chemotherapeutic doxorubicin (DOX) to glioblastoma. Accordingly, the ch-K5(s-s)R8-An/(Dbait-DOX) micelles plus radiotherapy (RT) treatment resulted in a high degree of apoptosis and DNA damage, which significantly reduced cell viability and proliferation capacity of U251 cells to 64.0% and 16.3%, respectively. The angiopep-2-modified micelles exhibited substantial accumulation in brain-localized U251 glioblastoma xenografts in mice compared to angiopep-2-lacking micelles. The ch-K5(s-s)R8-An/(Dbait-DOX) + RT treatment group exhibited the smallest tumor size and most profound tumor tissue injury in orthotopic U251 tumors, leading to an increase in median survival time of U251 tumor-bearing mice from 26 days to 56 days. The ch-K5(s-s)R8-An/(Dbait-DOX) micelles can be targeted to brain-localized U251 tumor xenografts and sensitize the tumor to chemotherapy and radiotherapy, thereby overcoming the inherent therapeutic challenges associated with malignant glioblastoma

Pre-Treatment with Melatonin Enhances Therapeutic Efficacy of Cardiac Progenitor Cells for Myocardial Infarction

Background/Aims: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. Methods: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation. MI model was used to evaluate the potential cardioprotective effects of melatonin and miR-98. Results: Melatonin attenuated H2O2-induced the proliferation reduction and apoptosis of c-kit+ CPCs in vitro, and CPCs which pretreated with melatonin significantly improved the functions of post-infarct hearts compared with CPCs alone in vivo. Melatonin was capable to inhibit the increase of miR-98 level by H2O2 in CPCs. The proliferation reduction and apoptosis of CPCs induced by H2O2 was aggravated by miR-98. In vivo, transplantation of CPCs with miR-98 silencing caused the more significant improvement of cardiac functions in MI than CPCs. MiR-98 targets at the signal transducer and activator of the transcription 3 (STAT3), and thus aggravated H2O2-induced the reduction of Bcl-2 protein. Conclusions: Pre-treatment with melatonin protects c-kit+ CPCs against oxidative stress-induced damage via downregulation of miR-98 and thereby increasing STAT3, representing a potentially new strategy to improve CPC-based therapy for MI

Impact of Short Food Videos on the Tourist Destination Image—Take Chengdu as an Example

Taking Chengdu as an example, based on the destination image theory and employing the content analysis methodology, this paper conducts data mining on the online comment texts of TikTok short food videos, and analyzes the impact of short food videos on the destination image (cognitive image, affective image and conative image). The results show that: (1) in terms of cognitive image, short food videos have increased potential tourists’ attention to the destination image, especially their attention to the flavor characteristics of food in the destination and the local social environment; (2) in terms of affective image, the comments of short food videos are mainly neutral and positive, and the contents about the flavor characteristics of food and the local social environment are more likely to affect the affective image of the destination; and (3) in terms of conative image, the appearance description of food in short food videos brings about an obvious effect of intention, and it also creates the demand to travel together and obtain information. This paper is inspiring for city managers and tourism marketers to use TikTok short videos to establish and disseminate food-based city brands and destination images

Drusen Segmentation From Retinal Images via Supervised Feature Learning

International audienc

Ultrafast charge transfer in a type-II MoS2-ReSe2 van der Waals heterostructure

We fabricated a van der Waals heterostructure by stacking together monolayers of MoS2 and ReSe2. Transient absorption measurements were performed to study the dynamics of charge transfer, indirect exciton formation, and indirect exciton recombination. The results show that the heterostructure form a type-II band alignment with the conduction band minimum and valance band maximum located in the MoS2 and ReSe2 layers, respectively. By using different pump-probe configurations, we found that electrons could efficiently transfer from ReSe2 to MoS2 and holes along the opposite direction. Once transferred, the electrons and holes form spatially indirect excitons, which have longer recombination lifetimes than excitons in individual monolayers. These results provide useful information for developing van der Waals heterostructure involving ReSe2 for novel electronic and optoelectronic applications