Magnetic Nanotweezers for Interrogating Biological Processes in Space and Time.

The ability to sense and manipulate the state of biological systems has been extensively advanced during the past decade with the help of recent developments in physical tools. Unlike standard genetic and pharmacological perturbation techniques-knockdown, overexpression, small molecule inhibition-that provide a basic on/off switching capability, these physical tools provide the capacity to control the spatial, temporal, and mechanical properties of the biological targets. Among the various physical cues, magnetism offers distinct advantages over light or electricity. Magnetic fields freely penetrate biological tissues and are already used for clinical applications. As one of the unique features, magnetic fields can be transformed into mechanical stimuli which can serve as a cue in regulating biological processes. However, their biological applications have been limited due to a lack of high-performance magnetism-to-mechanical force transducers with advanced spatiotemporal capabilities. In this Account, we present recent developments in magnetic nanotweezers (MNTs) as a useful tool for interrogating the spatiotemporal control of cells in living tissue. MNTs are composed of force-generating magnetic nanoparticles and field generators. Through proper design and the integration of individual components, MNTs deliver controlled mechanical stimulation to targeted biomolecules at any desired space and time. We first discuss about MNT configuration with different force-stimulation modes. By modulating geometry of the magnetic field generator, MNTs exert pulling, dipole-dipole attraction, and rotational forces to the target specifically and quantitatively. We discuss the key physical parameters determining force magnitude, which include magnetic field strength, magnetic field gradient, magnetic moment of the magnetic particle, as well as distance between the field generator and the particle. MNTs also can be used over a wide range of biological time scales. By simply adjusting the amplitude and phase of the applied current, MNTs based on electromagnets allow for dynamic control of the magnetic field from microseconds to hours. Chemical design and the nanoscale effects of magnetic particles are also essential for optimizing MNT performance. We discuss key strategies to develop magnetic nanoparticles with improved force-generation capabilities with a particular focus on the effects of size, shape, and composition of the nanoparticles. We then introduce various strategies and design considerations for target-specific biomechanical stimulations with MNTs. One-to-one particle-receptor engagement for delivering a defined force to the targeted receptor and the small size of the nanoparticles are important. Finally, we demonstrate the utility of MNTs for manipulating biological functions and activities with various spatial (single molecule/cell to organisms) and temporal resolution (microseconds to days). MNTs have the potential to be utilized in many exciting applications across diverse biological systems spanning from fundamental biology investigations of spatial and mechanical signaling dynamics at the single-cell and systems levels to in vivo therapeutic applications.

Prediction of Response to Stereotactic Radiosurgery for Brain Metastases Using Convolutional Neural Networks.

BACKGROUND: It is unclear whether radiomic phenotypes of brain metastases (BM) are related to radiation therapy prognosis. This study assessed whether a convolutional neural network (CNN)-based radiomics model which learned computer tomography (CT) image features with minimal preprocessing, could predict early response of BM to radiosurgery. MATERIALS AND METHODS: Tumor images of 110 BM post stereotactic-radiosurgery (SRS) (within 3 months) were assessed (Response Evaluation Criteria in Solid Tumor, version 1.1) as responders (complete or partial response) or non-responders (stable or progressive disease). Datasets were axial planning CT images containing the tumor center, and the tumor response. Datasets were randomly assigned to training, validation, or evaluation groups repeatedly, to create 50 dataset combinations that were classified into five groups of 10 different dataset combinations with the same evaluation datasets. The CNN learned using training-group images and labels. Validation datasets were used to choose the model that best classified evaluation images as responders or non-responders. RESULTS: Of 110 tumors, 57 were classified as responders, and 53 as non-responders. The area under the receiver operating characteristic curve (AUC) of each CNN model for 50 dataset combinations ranged from 0.602 [95% confidence interval (CI)=36.5-83.9%] to 0.826 [95% CI, 64.3-100%]. The AUC of ensemble models, which averaged prediction results of 10 individual models within the same group, ranged from 0.761 (95% CI=55.2-97.1%) to 0.856 (95% CI=68.2-100%). CONCLUSION: A CNN-based ensemble radiomics model accurately predicted SRS responses of unlearned BM images. Thus, CNN models are able to predict SRS prognoses from small datasets.

Prokinetic effects of LD02GIFRO on functional gastrointestinal disorder in rats.

LD02GIFRO is a novel prokinetic agent formulated with Poncirus fructus and Zanthoxylum sp. fruits. The aim of the present study was to evaluate the effect of LD02GIFRO on delayed gastrointestinal transit (GIT) and colorectal hypersensitivity. To investigate the effect of LD02GIFRO, a rat model of delayed GIT was induced via three mechanisms; postoperative ileus (POI), morphine, and POI plus morphine. Visceromotor responses (VMR) to colorectal distension (CRD) were also evaluated. POI was induced by laparotomy surgery and manipulation of the small intestine under anesthesia, and GIT was calculated by measuring the length that Evans Blue travelled through the gastrointestinal tract in a given time. Oral administration of 260 mg/kg LD02GIFRO caused Evans Blue to migrate significantly further in the delayed GIT models induced by POI, morphine and POI plus morphine compared with the control (P<0.05). This effect was inhibited by atropine, a muscarinic receptor antagonist, and completely abolished by GR125487, a 5-HT4-receptor antagonist. Furthermore, intraperitoneal administration of 600 and 900 mg/kg LD02GIFRO significantly reduced VMR to CRD in acute and chronic colorectal hypersensitive rat models, induced by acetic acid and trinitrobenzenesulfonic acid, to almost normal levels (P<0.01). In the present study, LD02GIFRO successfully ameliorated delayed GIT models and colorectal hypersensitivity models, suggesting that LD02GIFRO may be an effective therapeutic treatment for patients with functional gastrointestinal disorders and abnormalities in GIT.