The Transcription Factor MiMYB8 Suppresses Peel Coloration in Postharvest 'Guifei' Mango in Response to High Concentration of Exogenous Ethylene by Negatively Modulating MiPAL1.

Anthocyanin accumulation is regulated by specific genes during fruit ripening. Currently, peel coloration of mango fruit in response to exogenous ethylene and the underlying molecular mechanism remain largely unknown. The role of MiMYB8 on suppressing peel coloration in postharvest 'Guifei' mango was investigated by physiology detection, RNA-seq, qRT-PCR, bioinformatics analysis, yeast one-hybrid, dual-luciferase reporter assay, and transient overexpression. Results showed that compared with the control, low concentration of exogenous ethylene (ETH, 500 mg·L-1) significantly promoted peel coloration of mango fruit (cv. Guifei). However, a higher concentration of ETH (1000 mg·L-1) suppressed color transformation, which is associated with higher chlorophyll content, lower a* value, anthocyanin content, and phenylalanine ammonia-lyase (PAL) activity of mango fruit. M. indica myeloblastosis8 MiMYB8 and MiPAL1 were differentially expressed during storage. MiMYB8 was highly similar to those found in other plant species related to anthocyanin biosynthesis and was located in the nucleus. MiMYB8 suppressed the transcription of MiPAL1 by binding directly to its promoter. Transient overexpression of MiMYB8 in tobacco leaves and mango fruit inhibited anthocyanin accumulation by decreasing PAL activity and down-regulating the gene expression. Our observations suggest that MiMYB8 may act as repressor of anthocyanin synthesis by negatively modulating the MiPAL gene during ripening of mango fruit, which provides us with a theoretical basis for the scientific use of exogenous ethylene in practice.

Machine Learning Predicting Optimal Preparation of Silica-Coated Gold Nanorods for Photothermal Tumor Ablation.

Gold nanorods (GNRs) coated with silica shells are excellent photothermal agents with high surface functionality and biocompatibility. Understanding the correlation of the coating process with both structure and property of silica-coated GNRs is crucial to their optimizing preparation and performance, as well as tailoring potential applications. Herein, we report a machine learning (ML) prediction of coating silica on GNR with various preparation parameters. A total of 306 sets of silica-coated GNRs altogether were prepared via a sol-gel method, and their structures were characterized to extract a dataset available for eight ML algorithms. Among these algorithms, the eXtreme gradient boosting (XGboost) classification model affords the highest prediction accuracy of over 91%. The derived feature importance scores and relevant decision trees are employed to address the optimal process to prepare well-structured silica-coated GNRs. The high-throughput predictions have been adopted to identify optimal process parameters for the successful preparation of dumbbell-structured silica-coated GNRs, which possess a superior performance to a conventional cylindrical core-shell counterpart. The dumbbell silica-coated GNRs demonstrate an efficient enhanced photothermal performance in vivo and in vitro, validated by both experiments and time domain finite difference calculations. This study epitomizes the potential of ML algorithms combined with experiments in predicting, optimizing, and accelerating the preparation of core-shell inorganic materials and can be extended to other nanomaterial research.

Establishment and validation of novel MRI radiomic feature-based prognostic models to predict progression-free survival in locally advanced rectal cancer.

In locally advanced rectal cancer (LARC), an improved ability to predict prognosis before and after treatment is needed for individualized treatment. We aimed to utilize pre- and post-treatment clinical predictors and baseline magnetic resonance imaging (MRI) radiomic features for establishing prognostic models to predict progression-free survival (PFS) in patients with LARC. Patients with LARC diagnosed between March 2014 and May 2016 were included in this retrospective study. A radiomic signature based on extracted MRI features and clinical prognostic models based on clinical features were constructed in the training cohort to predict 3-year PFS. C-indices were used to evaluate the predictive accuracies of the radiomic signature, clinical prognostic models, and integrated prognostic model (iPostM). In total, 166 consecutive patients were included (110 vs. 56 for training vs. validation). Eleven radiomic features were filtered out to construct the radiomic signature, which was significantly related to PFS. The MRI feature-derived radiomic signature exhibited better prognostic performance than the clinical prognostic models (P = 0.007 vs. 0.077). Then, we proposed an iPostM that combined the radiomic signature with tumor regression grade. The iPostM achieved the highest C-indices in the training and validation cohorts (0.942 and 0.752, respectively), outperforming other models in predicting PFS (all P < 0.05). Decision curve analysis and survival curves of the validation cohort verified that iPostM demonstrated the best performance and facilitated risk stratification. Therefore, iPostM provided the most reliable prognostic prediction for PFS in patients with LARC.

1-Methylcyclopropene counteracts ethylene promotion of fruit softening and roles of MiERF2/8 and MiPG in postharvest mangoes.

Ethylene burst is an important sign of the initiation of postharvest mango ripening and softening is a typical characteristic of fruit ripening. However, the intrinsic link between ethylene release and fruit softening during ripening of postharvest mangoes is still not clear. The aim of this study was to investigate the effects of ethylene and its action inhibitor 1-methylcyclopropene (1-MCP) on fruit softening and ripening and the underlying regulatory mechanisms. Results showed that ethephon (ETH) promoted ethylene release and enhanced MDA content and activities of cell wall degrading enzymes, whereas 1-MCP treatment exhibited an opposite effect. Moreover, real-time quantitative polymerase chain reaction indicated that the transcription levels of genes involved in cell wall degradation (MiPG, Miß-GAL and MiPE), ethylene biosynthesis (MiACO1 and MiACS6) and ethylene response factor (MiERF8) were remarkably induced by ETH. Correlation analysis further revealed that the production of ethylene was significantly negatively correlated with firmness, but positively correlated with MDA content, activities of cell wall degrading enzymes and expressions of MiPG and Miß-GAL. Furthermore, yeast one hybrid (Y1H) assay showed that MiERF2 and MiERF8 could directly bind to the promotor of MiPG and then regulate its transcription. These findings suggest that ethylene production is closely associated with fruit softening, and MiERF2 and MiERF8 and MiPG may play crucial roles in regulation of ripening and softening of postharvest mangoes.

Synchronous enhancement of upconversion and NIR-IIb photoluminescence of rare-earth nanoprobes for theranostics.

This study develops a multifunctional molecular optical nanoprobe (SiO2@Gd2O3: Yb3+/Er3+/Li+@Ce6/MC540) with a unique core-satellite form. The rare-earth doped nanodots with good crystallinity are uniformly embedded on the surface of a hydrophilic silica core, and the nanoprobe can emit near-infrared-IIb (NIR-IIb) luminescence for imaging as well as visible light that perfectly matches the absorption bands of two included photosensitizers under 980 nm irradiation. The optimal NIR-IIb emission and upconversion efficiency are attainable via regulating the doping ratios of Yb3+, Er3+ and Li+ ions. The relevant energy transfer mechanism was addressed theoretically that underpins rare-earth photoluminescence where energy back-transfer and cross relaxation processes play pivotal roles. The nanoprobe can achieve an excellent dual-drive photodynamic treatment performance, verified by singlet oxygen detections and live-dead cells imaging assays, with a synergistic effect. And a brightest NIR-IIb imaging was attained in tumoral site of mouse. The nanoprobe has a high potential to serve as a new type of optical theranostic agent for tumor.

Invasiveness of a Growth-Migration System in a Two-dimensional Percolation cluster: A Stochastic Mathematical Approach.

We developed a framework based on the software Unstructured Reaction-Diffusion Master Equation (URDME) to address tumor cells' proliferation and migration in a heterogeneous space, herein a 2D percolation cluster. A mitogenic paracrine signaling pathway is utilized phenomenologically to reveal how cells cooperate with one another. We modeled the emerging Allee effect using low seeding density culture (LSDC) assays to fit the model parameters. A Finite time scaling (FTS) function has been formulated to quantitatively analyze invasiveness of a virtual Growth-Migration (GM) system in mimicking the cancer cell growth. Through such simulation, we analyzed the GM dynamics of virtual model in mimicking the growth of BT-474 cancer cell populations in vitro in a 2D percolation cluster and calculated the successful penetration rate (SPR). By analyzing the temporal trajectories of the SPR, we could determine the critical exponents of the critical SPR scaling relation. The SPR transition point ([Formula: see text]), which is a fundamentally different from a conventional percolation transition point, is found to be negatively correlated with the invasiveness of this cancer cell. The [Formula: see text] of the three variations of the virtual GM system distinctly designated by varying paracrine-regulated Allee (PAllee) model phenotypes is 0.3408, 0.3675, and 0.4454, respectively. FTS algorithm thereon may serve as an approach to quantify invasiveness of tumor cells. Through a phenomenological paracrine model, inter-cell cooperation and mutual mitogenic boosting are enabled to elicit the Allee effect in the GM systems. The rationale behind such computationally tunable virtual mechanism can be applied to other circumstances concerning emerging processes.

Exogenous Ethylene Promotes Peel Color Transformation by Regulating the Degradation of Chlorophyll and Synthesis of Anthocyanin in Postharvest Mango Fruit.

Due to geographical location and climatic factors, postharvest storage and preservation of tropical fruits and vegetables are still facing huge challenges. Ethephon (ETH) is widely used as an ethylene donor to achieve the commercial color and flavor of climacteric fruits. However, the effect of ETH on fruit coloration was affected by many factors, such as fruit species, plant hormones, and storage conditions. In this study, the main mango variety "Guifei" in Hainan, China, was used to study the effects of different concentrations of ETH on fruit ripening and coloration during storage at 25°C. Results showed that postharvest treatment with ETH (300, 500, and 900 mg·L-1) enhanced the activities of ACS and ACO, stimulated the release of endogenous ethylene, and accelerated fruit softening and color transformation. Compared with control, ETH treatment not only accelerated the breakdown of chlorophyll with higher activities of Chlase and MDCase but also induced the synthesis of carotenoid and anthocyanin with higher activities of PAL, CHI, DFR, and UFGT. Moreover, the changes in DFR and UFGT activities coincided with the increase in ETH concentration. Further, correlation analysis showed that the production of endogenous ethylene induced by ETH was significantly negatively correlated with firmness and chlorophyll content, whereas positively correlated with MDA content and anthocyanin content. This study suggests that the positive effect of ETH on "Guifei" mango color transformation is concentration-dependent within a certain concentration range. Anthocyanin is the main pigment for the red formation of "Guifei" mango, and DFR and UFGT may play critical roles in anthocyanin synthesis. ETH promoted the red coloration by promoting the release of endogenous ethylene and enhancing the activities of anthocyanin synthesis enzymes.

Differences in Radiomics Signatures Between Patients with Early and Advanced T-Stage Nasopharyngeal Carcinoma Facilitate Prognostication.

BACKGROUND: Accurately predicting the risk of death, recurrence, and metastasis of patients with nasopharyngeal carcinoma (NPC) is potentially important for personalized diagnosis and treatment. Survival outcomes of patients vary greatly in distinct stages of NPC. Prognostic models of stratified patients may aid in prognostication. PURPOSE: To explore the prognostic performance of MRI-based radiomics signatures in stratified patients with NPC. STUDY TYPE: Retrospective. POPULATION: Seven hundred and seventy-eight patients with NPC (T1-2 stage: 298, T3-4 stage: 480; training cohort: 525, validation cohort: 253). FIELD STRENGTH/SEQUENCE: Fast-spin echo (FSE) axial T1-weighted images, FSE axial T2-weighted images, contrast-enhanced FSE axial T1-weighted images at 1.5 T or 3.0 T. ASSESSMENT: Radiomics signatures, clinical nomograms, and radiomics nomograms combining the radiomic score (Radscore) and clinical factors for predicting progression-free survival (PFS) were constructed on T1-2 stage patient cohort (A), T3-4 stage patient cohort (B), and the entire dataset (C). STATISTICAL TESTS: Least absolute shrinkage and selection operator (LASSO) method was applied for radiomics modeling. Harrell's concordance indices (C-index) were employed to evaluate the predictive power of each model. RESULTS: Among 4,410 MRI-extracted features, we selected 16, 16, and 14 radiomics features most relevant to PFS for Models A, B, and C, respectively. Only 0, 1, and 4 features were found overlapped between models A/B, A/C, and B/C, respectively. Radiomics signatures constructed on T1-2 stage and T3-4 stage patients yielded C-indices of 0.820 (95% confidence interval [CI]: 0.763-0.877) and 0.726 (0.687-0.765), respectively, which were larger than those on the entire validation cohort (0.675 [0.637-0.713]). Radiomics nomograms combining Radscore and clinical factors achieved significantly better performance than clinical nomograms (P < 0.05 for all). DATA CONCLUSION: The selected radiomics features and prognostic performance of radiomics signatures differed per the type of NPC patients incorporated into the models. Radiomics models based on pre-stratified tumor stages had better prognostic performance than those on unstratified dataset. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 5.

Effect of ethanol fumigation on pericarp browning associated with phenol metabolism, storage quality, and antioxidant systems of wampee fruit during cold storage.

Wampee fruit is a popular fruit cultivar in South-East Asia due to its high levels of nutrients and antioxidants; however, pericarp browning leads to a short storage life with great economic loss during years. The purpose of this work was to determine whether postharvest ethanol fumigation affected pericarp browning development of wampee fruit during 12 days of storage at 8 ± 0.5°C, and if so, how it is related to phenol metabolism and how it affects quality attributes and antioxidant systems during storage. After fruits were fumigated with 100, 300, 500, and 800 µl/L for 5 hr at 22 ± 0.5°C, ethanol significantly reduced the development of pericarp browning by increasing total phenolics (TP) content and decreasing the activity of polyphenol oxidase (PPO), especially in 500 µl/L ethanol treatment. Additionally, ethanol delayed the losses in fruit firmness (FF), soluble solid content (SSC), and titratable acidity (TA), retarded weight loss and accumulation of malondialdehyde (MDA) content and maintained relatively high contents of ascorbic acid (AsA), total flavonoids (TF), and total antioxidant capacity (TAC) and activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). In conclusion, results demonstrated that postharvest ethanol fumigation in wampee fruit has ability to reduce pericarp browning development by regulating phenol metabolism and enhancing antioxidant systems.

Nanoassembly and Multiscale Computation of Multifunctional Optical-Magnetic Nanoprobes for Tumor-Targeted Theranostics.

Gold nanorods, mesoporous silica, gadolinia, folic acid, and polyethylene glycol (PEG) derivatives have been investigated due to their own advantages in cancer theranostics. However, it remains a great challenge to assemble these components into a stable unity with the diverse and enhanced functionality for more potential applications. Herein, as inspired by the first-principles calculation, a highly stable and safe all-in-one nanoprobe is fabricated via a novel nanoassembly strategy. Multiscale calculations were performed to address the atomistic bonding of a nanoprobe, heat necrosis of a tumor adjacent to the vasculature, and thermal diffusion in a photothermal circumstance, respectively. The nanoprobe gains an 8-fold increase in magnetic resonance imaging (MRI) relaxivity compared to the clinical gadolinium diethylenetriaminepentaacetate, achieving a significant MRI signal in vivo. Conjugated with folate-PEG, the nanoprobe can be effectively absorbed by tumoral cells, obtaining a vivid two-photon cell imaging. A specific multisite scheme for photothermal therapy of a solid tumor is proposed to improve low photothermal efficacy caused by thermal diffusion in a large tumor, leading to the successful cure of the mice with xenograft tumor sized 10-12 mm. In vitro and in vivo toxicity, long-term excretion data, and the recovery of the treated mice demonstrate that the theranostic nanoprobe possesses good biocompatibility and metabolism efficacy.

Spatiotemporal dynamics of different growth-diffusion systems on a percolation lattice.

To investigate the proliferation and invasion of a tumor within an inhomogeneous matrix, we studied the spatiotemporal dynamics of two types of growth-diffusion systems (GDSs) with logistic or Allee growth occurring on a two-dimensional square site percolation lattice via numerical computation and finite-size scaling approaches. A critical percolation threshold exists in the two systems, but becomes obscure with an increasing Allee effect in Allee growth. The two systems evidently differ in their short-time spatiotemporal patterns: The tumor number density in the logistic model grows and spreads continuously and subdiffusively or weakly superdiffusively while that in the Allee model does so discretely and strongly superdiffusively. This difference is attributed to a lack of cooperation between sites for growth and diffusion in the logistic model as compared to its Allee counterpart. The Allee growth pattern is characterized by a rougher border and more inhomogeneous interior than its logistic counterpart. Judging from their growth-diffusion feature in combination with a clinical image analysis, we conclude that Allee growth is more suitable for modeling the proliferation and invasion of an early-stage malignant tumor than is logistic growth. A phase diagram that correlates a tumor's growth and diffusion on a percolation lattice with a site occupation fraction and Allee effect was established to reveal the sensitivity on proliferation and spreading of a tumor towards the above parameters. The Allee effect was also found to induce diverse dynamic features on its short-time growth and diffusion in the GDS, which brings in an opposite trend toward a tumor's growth and diffusion.

Dysprosium-doped iron oxide nanoparticles boosting spin-spin relaxation: a computational and experimental study.

Early diagnosis of diseases by contrast-enhanced magnetic resonance imaging (MRI) using iron oxide superparamagnetic nanoparticles (IOSNPs) has been extensively investigated due to the good biocompatibility of modified IOSNPs. However, the low magnetic sensitivity of IOSNPs still inflicts a certain limitation on their further application. In this study, we employed first-principles calculations based on spin-polarized density functional theory (SDFT) to find the optimal dysprosium-doped scheme for improving the magnetic sensitivity of IOSNPs. Elicited from the optimal doping scheme, we synthesized a sort of ultrasmall γ-iron oxide superparamagnetic nanoparticle by a special phase transfer-coprecipitation method. The appropriately Dy-doped γ-IOSNPs coated with short-chain polyethylene glycol are small in hydrodynamic size and highly dispersed with effectively improved superparamagnetism for enhancing T2-weighted MRI relaxivity, which is well consistent with the SDFT prediction. The measured spin-spin relaxivity r2 is 123.2 s-1 mM-1, nearly double that of the pure γ-IOSNPs (67.8 s-1 mM-1) and substantially surpassing that of both clinically-approved T2 contrast agents Feridex and Resivist. The low dysprosium doping does not induce notable nanotoxicity for IOSNPs, but contributes sufficiently to their high relaxation performance instead, which endows the Dy-doped γ-IOSNPs with high potential as a better T2-weighted MRI contrast medium. Both the method and the nanomagnets reported in this study are expected to promote studies on designing and preparing high-performance MRI contrast agents as well as computational materials.

The value of detailed MR imaging report of primary tumor and lymph nodes on prognostic nomograms for nasopharyngeal carcinoma after intensity-modulated radiotherapy.

PURPOSE: To establish effective prognostic nomograms using clinical features and detailed magnetic resonance imaging (MRI) findings for primary tumor and regional lymph nodes after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma. METHOD: The nomogram for overall survival (OS) was based on a retrospective study of 595 patients who underwent IMRT at Sun Yat-sen University Cancer Center from 2010 to 2012. The predictive accuracy and discriminative ability of our nomogram models were determined by concordance index and calibration curve, and were compared with the nomogram models combining clinical features with tumor-node-metastasis (TNM) classification. The results were validated using bootstrap resampling and a cohort study of 241 patients. The same data cohort was used to predict the progress-free survival (PFS) of nasopharyngeal carcinoma with 3:1 training cohort (N = 558) and validation cohort (N = 278). RESULTS: The following factors were assembled into our prognostic survival nomogram models: Age, Epstein-Barr virus DNA copy number before treatment (EBV_DNA_CN), tensor veli palatini (TVP) involvement, musculus pterygoideus lateralis (MPL) involvement, prestyloid space (PS) involvement, prevertebral space (PVS) involvement, base of sphenoid bone (BOSB) involvement, paranasal sinus (PNS) involvement, the laterality of Ⅱ (Ⅱ_laterality), the laterality of retropharyngeal lymph node (RPLN_laterality), nodal grouping (NG), extranodal neoplastic spread (ENS), contrast-enhancing rim (CER) and Nodal_number. The calibration curves showed good agreement between nomogram-predicted and actual survival. Our nomogram models for OS and PFS, provided better results than the nomogram models combining clinical features with TNM classification. Results were further confirmed in the validation set. CONCLUSION: Detailed MRI findings of primary tumor and regional lymph nodes can improve the performance of prognostic nomograms for patients with nasopharyngeal carcinoma.

MRI relaxivity enhancement of gadolinium oxide nanoshells with a controllable shell thickness.

Gadolinium oxide-based core-shelled nanoparticles have recently emerged as novel magnetic resonance imaging contrast agents for high relaxivity and tumor targeting. However, their relaxivity enhancement mechanism has not yet been clearly understood. We prepared highly dispersible and uniform core-shell structured nanoparticles by encapsulating silica spheres (90 nm in diameter) with gadolinium oxide shells of different thicknesses (from 1.5 nm to 20 nm), and proved experimentally that the shell thickness has an inverse effect on relaxivity. The core-shelled nanoparticles are of a larger relaxivity than the commercial contrast agent Gd-DTPA, with an enhancement from 1.8 to 7.3 times. Based on the Solomon-Bloembergen-Morgan theory which is usually adopted for interpreting the relaxation changes of water protons in Gd3+ chelates, we introduced a shielding ansatz of nanoshells and derived a concise formula specifically to correlate the relaxivity of this sort of core-shelled nanoparticles with the shell thickness directly. The formula calculation is well consistent with the experimental results, and the formula can be generally applied to evaluate the relaxation enhancement underlying the high relaxivity of any core-shelled nanoparticle. Furthermore, the core-shelled nanoparticles possess a negligible nanotoxicity according to the in vitro cytotoxicity and in vivo histopathology and hematology assays. The enhanced signals of in vivo tumor-targeted magnetic resonance imaging indicate that the ultrathin gadolinium oxide nanoshells may function as a potential candidate for advanced positive contrast agents in further clinical applications.

Tumor-targeted nanoprobes for enhanced multimodal imaging and synergistic photothermal therapy: core-shell and dumbbell Gd-tailored gold nanorods.

Multifunctional nanoprobes, due to their unique nanocomposite structures, have prominent advantages that combine multimodal imaging of a tumor with photothermal therapy. However, they remain a challenge for constructing nanostructures via conventional approaches due to the peculiar environmental sensitivity of each component. Here, we report the design and synthesis of Gd-based nanoparticle-tailored gold nanorods with distinctive core-shell and dumbbell nanoarchitectures (NAs) by a specific synthesis technology. The prepared NAs possess a tunable particle size of 80-120 nm in length and 50-90 nm in diameter, which are suitable for cellular uptake and passive targeting of a tumor. The formation of two distinct heterostructures and their underlying mechanism were studied through systematic investigations on the controllable synthesis process. The as-prepared nanoprobes possess an ultrahigh longitudinal relaxivity (r1) of 22.69 s-1 mM-1 and thus a significant magnetic resonance imaging signal enhancement has been observed in mice tumors. The NAs, especially the dumbbell type, show a vivid two-photon cell imaging and a remarkable photothermal conversion efficiency owing to their superior longitudinal surface plasmon resonance. Both in vitro cytotoxicity and in vivo immunotoxicity assays give substantial evidence of excellent biocompatibility attained in the NAs. The development of multifunctional targeting nanoprobes in this study could provide guidance for tailored design and controllable synthesis of heterostructured nanocomposites utilized for multimodal imaging and photothermal therapy of cancer.

Magnetic and fluorescent Gd2O3:Yb3+/Ln3+ nanoparticles for simultaneous upconversion luminescence/MR dual modal imaging and NIR-induced photodynamic therapy.

The development of upconversion nanoparticles (UCNs) for theranostics application is a new strategy toward the accurate diagnosis and efficient treatment of cancer. Here, magnetic and fluorescent lanthanide-doped gadolinium oxide (Gd2O3) UCNs with bright upconversion luminescence (UCL) and high longitudinal relaxivity (r1) are used for simultaneous magnetic resonance imaging (MRI)/UCL dual-modal imaging and photodynamic therapy (PDT). In vitro and in vivo MRI studies show that these products can serve as good MRI contrast agents. The bright upconversion luminescence of the products allows their use as fluorescence nanoprobes for live cells imaging. We also utilized the luminescence-emission capability of the UCNs for the activation of a photosensitizer to achieve significant PDT results. To the best of our knowledge, this study is the first use of lanthanide-doped Gd2O3 UCNs in a theranostics application. This investigation provides a useful platform for the development of Gd2O3-based UCNs for clinical diagnosis, treatment, and imaging-guided therapy of cancer.

High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells.

Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.

Tumor proliferation and diffusion on percolation clusters.

We study in silico the influence of host tissue inhomogeneity on tumor cell proliferation and diffusion by simulating the mobility of a tumor on percolation clusters with different homogeneities of surrounding tissues. The proliferation and diffusion of a tumor in an inhomogeneous tissue could be characterized in the framework of the percolation theory, which displays similar thresholds (0.54, 0.44, and 0.37, respectively) for tumor proliferation and diffusion in three kinds of lattices with 4, 6, and 8 connecting near neighbors. Our study reveals the existence of a critical transition concerning the survival and diffusion of tumor cells with leaping metastatic diffusion movement in the host tissues. Tumor cells usually flow in the direction of greater pressure variation during their diffusing and infiltrating to a further location in the host tissue. Some specific sites suitable for tumor invasion were observed on the percolation cluster and around these specific sites a tumor can develop into scattered tumors linked by some advantage tunnels that facilitate tumor invasion. We also investigate the manner that tissue inhomogeneity surrounding a tumor may influence the velocity of tumor diffusion and invasion. Our simulation suggested that invasion of a tumor is controlled by the homogeneity of the tumor microenvironment, which is basically consistent with the experimental report by Riching et al. as well as our clinical observation of medical imaging. Both simulation and clinical observation proved that tumor diffusion and invasion into the surrounding host tissue is positively correlated with the homogeneity of the tissue.

A computer-aided diagnosis system for dynamic contrast-enhanced MR images based on level set segmentation and ReliefF feature selection.

This study established a fully automated computer-aided diagnosis (CAD) system for the classification of malignant and benign masses via breast magnetic resonance imaging (BMRI). A breast segmentation method consisting of a preprocessing step to identify the air-breast interfacing boundary and curve fitting for chest wall line (CWL) segmentation was included in the proposed CAD system. The Chan-Vese (CV) model level set (LS) segmentation method was adopted to segment breast mass and demonstrated sufficiently good segmentation performance. The support vector machine (SVM) classifier with ReliefF feature selection was used to merge the extracted morphological and texture features into a classification score. The accuracy, sensitivity, and specificity measurements for the leave-half-case-out resampling method were 92.3%, 98.2%, and 76.2%, respectively. For the leave-one-case-out resampling method, the measurements were 90.0%, 98.7%, and 73.8%, respectively.

The anomalous diffusion of a tumor invading with different surrounding tissues.

We simulated the invasion of a proliferating, diffusing tumor within different surrounding tissue conditions using a hybrid mathematical model. The in silico invasion of a tumor was addressed systematically for the first time within the framework of a generalized diffusion theory. Our results reveal that a tumor not only migrates using typical Fickian diffusion, but also migrates more generally using subdiffusion, superdiffusion, and even ballistic diffusion, with increasing mobility of the tumor cell when haptotaxis and chemotaxis toward the host tissue surrounding the proliferative tumor are involved. Five functional terms were included in the hybrid model and their effects on a tumor's invasion were investigated quantitatively: haptotaxis toward the extracellular matrix tissue that is degraded by matrix metalloproteinases; chemotaxis toward nutrients; cell-cell adhesion; the proliferation of the tumor; and the immune response toward the tumor. Haptotaxis and chemotaxis, which are initiated by extracellular matrix and nutrient supply (i.e., glucose) respectively, as well as cell-cell adhesions all drastically affect a tumor's diffusion mode when a tumor invades its surrounding host tissue and proliferates. We verified the in silico invasive behavior of a tumor by analyzing experimental data gathered from the in vitro culturing of different tumor cells and clinical imaging observations that used the same approach as was used to process the simulation data. The different migration modes of a tumor suggested by the simulations generally conform to the results observed in cell cultures and in clinical imaging. Our study not only discloses some migration modes of a tumor that proliferates and invades under different host tissues conditions, but also provides a heuristic method to characterize the invasion of a tumor in clinical medical imaging analysis.