An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized ³He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B₀ coil design that produces an optimized 65 G (6.5 mT) magnetic field for ³He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D ³He images with up to 2.8 mm resolution, and present initial 2D and 3D ³He images of human lungs in both supine and upright orientations. ¹H MRI can also be performed for diagnostic and calibration reasons.     

Carbon Dots‐Cluster‐DOX Nanocomposites Fabricated by a Co‐Self‐Assembly Strategy for Tumor‐Targeted Bioimaging and Therapy

Carbon‐based nanomaterials could afford versatile potential applications in biomedical optical imaging and as nanoparticle drug carriers, owing to their promising optical and biocompatible capabilities. In this paper, it is first found that amphipathic cetylpyridinium chloride (CPC)‐stabilized oil‐soluble carbon dots (CDs) could self‐assemble into hydrophilic CDs clusters with hydrophobic core under ultrasound, in which CPC acts as carbon source, stabilizer, and phase transfer agent. Next, the size‐control (for size‐dependent passive tumor targeting) and doxorubicin (DOX) uploading of aqueous CDs clusters, and subsequent surface charge modification via overcoating with cRGD‐ and octylamine‐modified polyacrylic acid (cRGD‐PAA‐OA) (reversing their surface charges into negative and introducing active tumor‐targeting ability) are explored systematically. Based on this sequential administration mode, CDs‐cluster‐DOX/cRGD‐PAA‐OA nanocomposites exhibit selective human malignant glioma cell line (U87MG) tumor targeting. In in vitro drug release experiments, the nanocomposites could release DOX timely. Owning to the dual tumor targeting effects and seasonable drug release, CDs‐cluster‐DOX/cRGD‐PAA‐OA show remarkably tumor targetability and enhanced antitumor efficacy (and reduced adverse reaction), comparing to free DOX in animal models. These results indicate that fabricating nanocomposite via co‐self‐assembly strategy is efficient toward drug delivery system for tumor‐targeting theranostic.     

A Cahn‐Hilliard–type equation with application to tumor growth dynamics

We consider a Cahn‐Hilliard–type equation with degenerate mobility and single‐well potential of Lennard‐Jones type. This equation models the evolution and growth of biological cells such as solid tumors. The degeneracy set of the mobility and the singularity set of the cellular potential do not coincide, and the absence of cells is an unstable equilibrium configuration of the potential. This feature introduces a nontrivial difference with respect to the Cahn‐Hilliard equation analyzed in the literature. We give existence results for different classes of weak solutions. Moreover, we formulate a continuous finite element approximation of the problem, where the positivity of the solution is enforced through a discrete variational inequality. We prove the existence and uniqueness of the discrete solution for any spatial dimension together with the convergence to the weak solution for spatial dimension d=1. We present simulation results in 1 and 2 space dimensions. We also study the dynamics of the spinodal decomposition and the growth and scaling laws of phase ordering dynamics. In this case, we find similar results to the ones obtained in standard phase ordering dynamics and we highlight the fact that the asymptotic behavior of the solution is dominated by the mechanism of growth by bulk diffusion.     

Blocking ACAT‐1 Activity for Tumor Therapy with Fluorescent Hyperstar Polymer‐Encapsulated Avasimible

Targeting the distinct cholesterol metabolism of tumor cells is proposed as a novel way to treat tumors. Blocking acyl‐CoA cholesterol acyltransferase‐1 (ACAT‐1) by the inhibitor avasimible (Ava), which elevates intracellular free cholesterol levels, is shown to effectively induce apoptosis. However, Ava faces disadvantages of poor water solubility, a short half‐life, and no capability for fluorescence detection, which have greatly limited its application. Herein, a fluorescent hyperstar polymer (FHSP) is developed to encapsulate Ava to improve its ability to inhibit HeLa cells and K562 cells. The results of this study show that the obtained Ava–FHSP micelles possess a high drug loading capacity of 22.7% and bright green fluorescence. Ava and Ava–FHSP are cytotoxic to both HeLa and K562 cells and cause reductions in cell size, nuclear lysis, and chromatin condensation and hindered proliferation of both cell types by causing S phase cell cycle arrest. Further mechanistic analysis indicates that Ava–FHSP reduces the protein and messenger RNA expression of ACAT‐1 and significantly increases intracellular free cholesterol levels, which can increase endoplasmic reticulum stress and finally cause cell apoptosis. All these results suggest that this fluorescent hyperstar polymer represents a potential therapeutic tumor strategy by changing the cholesterol metabolism of tumor cells.     

Intracellular Entropy-Driven Multi-Bit DNA Computing for Tumor Progression Discrimination

Tumor progressions such as metastasis are complicated events that involve abnormal expression of different miRNAs and enzymes. Monitoring these biomolecules in live cells with computational DNA nanotechnology may enable discrimination of tumor progression via digital outputs. Herein, we report intracellular entropy-driven multivalent DNA circuits to implement multi-bit computing for simultaneous analysis of intracellular telomerase and microRNAs including miR-21 and miR-31. These three biomolecules can trigger respective DNA strand displacement recycling reactions for signal amplification. They are visualized by fluorescence imaging, and their signal outputs are encoded as multi-bit binary codes for different cell types. The results can discriminate non-tumorigenic, malignant and metastatic breast cells as well as respective tumors. This DNA computing circuit is further performed in a microfluidic chip to differentiate rare co-cultured cells, which holds a potential for the analysis of clinical samples.     

常规肺通气功能检测在儿童支气管哮喘规范化管理中的应用

目的 通过对比支气管哮喘患儿规范化治疗前后肺功能指标的变化,为本地区儿童哮喘规范化管理提供依据。方法 采用肺功能测定系统对33 例哮喘儿童在急性发作期、缓解期3、6 个月及1 年分别进行常规肺通气功能测定,比较各期实测值,以及异常比例的差异。结果 哮喘患儿急性发作期用力肺活量（FVC）、1 秒用力呼气量（FEV1）、最大呼气流量（PEF）及75%、50%、25%肺活量时用力呼气流速（FEF25~75）等实测值与预计值比较均下降,规范化治疗后3个月开始相关指标逐渐恢复,6个月后反映大气道功能相关指标（FVC、FEV1等）基本恢复。1年时反映小气道功能相关指标FEF25~75 恢复。结论 通过对支气管哮喘儿童肺功能的监测,可以动态观察患儿气道功能恢复情况,为儿童支气管哮喘规范化管理提供客观依据。     

Efficient One-Pot Synthesis of Doxorubicin Conjugates Through Its Amino Group to Melanotransferrin P97

Abstract

The amino group of doxorubicin 1 is reacted with bis-NHS-ester linkers 6, or anhydrides 13 to offer in high yield modified doxorubicins 7–12 and 14–16, respectively. Compounds 7–12 are mono-NHS-esters, and can be directly coupled with melanotransferrin (p97), a useful vector with the ability to cross the blood-brain barrier, to yield the expected doxorubicin-p97 conjugates. Upon activating the carboxylic group with BTTU, compound 14–16 could be used in the same reaction. Structurally, the amino group of doxorubicin is covalently bonded to the amino groups of p97. The conjugates are potential candidates for treatment of brain tumors.     

分子影像新技术——氘代谢波谱及成像的综述与展望

目前常用的分子影像技术主要有正电子发射型断层显像（PET）、质子磁共振波谱（¹H MRS）及成像（¹H MRSI）、化学交换饱和转移（CEST）、超极化¹³C MRSI等.近4年来,氘代谢波谱（DMS）及成像（DMI）作为一种新兴的分子影像技术获得了越来越多的关注,其通过采集注射或口服氘代葡萄糖后的目标组织与正常组织间氘代谢产物的磁共振信号进行组织区分.相比于其他分子影像方法,该影像技术具有无辐射、稳定性好、扫描操作相对简单等优点.本文综述了近年来DMS/DMI技术的研究进展及其意义,归纳总结了其临床应用价值,并对该技术未来的发展和改进方向,以及应用前景进行了展望.