Modeling Three-dimensional Invasive Solid Tumor Growth in Heterogeneous Microenvironment under Chemotherapy

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations reproduce the well-established observation that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.Comment: 41 pages, 8 figure

Fluctuating Two-state Light Harvesting In A Photosynthetic Membrane

The mechanism by which light is converted into chemical energy in a natural photosynthetic system has drawn considerable research interest. Using fluorescence spectroscopy and microscopic imaging, we have observed fluctuating intermolecular protein fluorescence resonant energy transfers (FRET) among light-harvesting proteins I and II (LH1 and LH2) in bacterial photosynthetic membranes. Using two-channel, FRET, photon-counting detection and a novel, two-dimensional cross-correlation function amplitude-mapping analysis, we revealed fluorescence intensity and spectral fluctuations of donor (LH2) and acceptor (LH1) fluorescence involving FRET. Our results suggest that there are dynamic coupled and noncoupled states of the light-harvesting protein assemblies in photosynthetic membranes. The light-harvesting complex assembly under ambient conditions and under water involves dynamic intermolecular structural fluctuations that subsequently disturb the degree of energy transfer coupling between proteins in the membrane. Such intrinsic and dynamic heterogeneity of the native photosynthetic membranes, often submerged under the overall thermally induced spectral fluctuations and not observable in an ensemble-averaged measurement, likely plays a critical role in regulating the light-harvesting efficiency of the photosynthetic membranes

The value of VI-RADS combined with tumor contact length in the detection of muscle-invasive bladder cancer

Background and purpose: The value of Vesical Imaging-Reporting and Data System (VI-RADS) based on multiparametric magnetic resonance imaging (MRI) in the preoperative assessment of bladder cancer muscle-invasive is increasingly recognized. However, there is still a high number of false positives when the diagnostic cut-off value is 3 points. Tumor size has certain auxiliary diagnostic value in the assessment of tumor infiltration. Therefore, this study mainly explored the diagnostic performance of VI-RADS combined with tumor size in assessing bladder cancer muscle-invasive. Methods: The preoperative bladder multiparametric MRI and clinical data of 119 patients with bladder cancer confirmed by surgery and pathology (a total of 159 lesions) who were treated in Fudan University Shanghai Cancer Center from November 2019 to February 2022 were retrospectively collected. VI-RADS score and tumor contact length (TCL) measurements were performed independently for each lesion by two radiologists. Lesions with differences in score or size were given consistent results following discussion by two physicians. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of VI-RADS, TCL and their combined models for muscle invasion, and the corresponding area under curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were compared. Results: Postoperative pathology confirmed that there were 75 and 84 lesions of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. The mean TCL of MIBC group (6.15-6.23 cm) was significantly different from that of NMIBC group (2.26-2.35 cm), and the difference was statistically significant (P<0.05). The specificity, PPV and diagnostic accuracy of VI-RADS combined with TCL in predicting bladder cancer muscle-invasive were significantly higher than those of VI-RADS with a diagnostic threshold of 3 points alone (P<0.05), whereas there was no statistically significant difference in the sensitivity and NPV (P>0.05). There was no significant difference in AUC between TCL (AUC = 0.89), VI-RADS (AUC = 0.90) and VI-RADS combined with TCL (AUC = 0.91) (P>0.05). Conclusion: VI-RADS combined with TCL can reduce the false positive rate of VI-RADS 3-point lesions in the evaluation of bladder cancer muscle-invasive to a certain extent, which is beneficial for avoiding overtreatment

Single Molecule Spectroscopy of Electron Transfer

The objectives of this research are threefold: (1) to develop methods for the study electron transfer processes at the single molecule level, (2) to develop a series of modifiable and structurally well defined molecular and nanoparticle systems suitable for detailed single molecule/particle and bulk spectroscopic investigation, (3) to relate experiment to theory in order to elucidate the dependence of electron transfer processes on molecular and electronic structure, coupling and reorganization energies. We have begun the systematic development of single molecule spectroscopy (SMS) of electron transfer and summaries of recent studies are shown. There is a tremendous need for experiments designed to probe the discrete electronic and molecular dynamic fluctuations of single molecules near electrodes and at nanoparticle surfaces. Single molecule spectroscopy (SMS) has emerged as a powerful method to measure properties of individual molecules which would normally be obscured in ensemble-averaged measurement. Fluctuations in the fluorescence time trajectories contain detailed molecular level statistical and dynamical information of the system. The full distribution of a molecular property is revealed in the stochastic fluctuations, giving information about the range of possible behaviors that lead to the ensemble average. In the case of electron transfer, this level of understanding is particularly important to the field of molecular and nanoscale electronics: from a device-design standpoint, understanding and controlling this picture of the overall range of possible behaviors will likely prove to be as important as designing ia the ideal behavior of any given molecule

Does China’s iron ore futures market have price discovery function? Analysis based on VECM and State-space perspective

As the world’s largest importer, trading of iron ore occupies a pivotal position in China’s international trade. In order to seek the decision power of deciding the price for iron ore, China’s Dalian Commodity Exchange (DCE) listed iron ore futures in October 2013,which has become the world’s largest iron ore financial derivatives trading market now. Based on VECM and state-space perspective, this paper aims to explore the price discovery function of iron ore futures on the DCE. Comprehensive analysis from the views of long-term equilibrium relationship, short-term information shocks and dynamic contribution share are made in this paper. The empirical results show that: firstly, from the perspective of cointegration test, there is a long-term equilibrium relationship between the futures prices in DCE and the spot prices; secondly, when facing with short-term information shocks, iron ore futures in DCE have an obviously price discovery function by the analysis of impulse response and variance decomposition; finally, by the way of state-space and Kalman filter algorithm, the long-term equilibrium relationship dynamic contribution for price discovery function of DCE's iron ore futures remains stable between 60% and 70% now

Morphological quantification of proliferation-to-invasion transition in tumor spheroids

Abstract(#br)Background(#br)Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential. However, the mechanism is still unclear and especially, the proliferation-to-metastasis/invasion transition point has not been well defined. Therefore, quantitative characterization of this transition is urgently needed.(#br)Methods(#br)We have successfully developed a home-built living-cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor-cell spheroids in a collagen fiber scaffold.(#br)Results(#br)The system focuses on in vitro tumor modeling, e.g. the development of tumor-cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDA-MB-231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation-to-invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug application.(#br)Conclusions(#br)Our quantitative approach provides a feasible clarification for the proliferation-to-invasion transition of in vitro tumor models (spheroids). Moreover, the transition time is a useful reference for the invasive potential of tumor cells.(#br)General significance(#br)This quantitative approach is potentially applicable to primary tumor cells, and thus has potential applications in the fields of cancer metastasis investigations and clinical diagnostics

Hybrid Organic/Inorganic Nanocomposites for Photovoltaic Cells

Inorganic/organic hybrid solar cells have attracted a lot of interest due to their potential in combining the advantages of both components. To understand the key issues in association with photoinduced charge separation/transportation processes and to improve overall power conversion efficiency, various combinations with nanostructures of hybrid systems have been investigated. Here, we briefly review the structures of hybrid nanocomposites studied so far, and attempt to associate the power conversion efficiency with these nanostructures. Subsequently, we are then able to summarize the factors for optimizing the performance of inorganic/organic hybrid solar cells