Design of an Injectable Magnetic Hydrogel Based on the Tumor Microenvironment for Multimodal Synergistic Cancer Therapy.

Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application. Drug delivery systems (DDSs) based on nanomaterials have attracted wide interest in cancer treatment; especially, the system can realize efficient synergistic therapies. Here, we designed a smart hydrogel drug delivery system with multiple responses to enhance the tumor treatment effect. By cross-linking oxidized hydroxypropyl cellulose with carboxymethyl chitosan, an injectable hydrogel was obtained, into which artesunate (ART), ferroferric oxide (Fe3O4) nanoparticles, and black phosphorus nanosheets (BPs) were preloaded. This DDS has multiple functions including magnetic targeting, pH sensitivity, chemodynamic therapy, and photothermal response. This nanoparticle-composited hydrogel not only preserved excellent rheological properties but also allowed for an accurate stable drug release at tumor sites and synergistic effects of multiple therapies. The in vitro and in vivo experiments revealed that this DDS could efficiently eliminate the HepG2 tumor with good biocompatibility. Taken together, this study clarifies the possible antitumor mechanism of this ART-loaded nanoparticle-composited hydrogel and provides a new strategy for synergistic photothermal-chemo-chemodynamic therapy.

Doxorubicin-based ENO1 targeted drug delivery strategy enhances therapeutic efficacy against colorectal cancer.

Alpha-enolase (ENO1), a multifunctional protein with carcinogenic properties, has emerged as a promising cancer biomarker because of its differential expression in cancer and normal cells. On the basis of this characteristic, we designed a cell-targeting peptide that specifically targets ENO1 and connected it with the drug doxorubicin (DOX) by aldehyde-amine condensation. A surface plasmon resonance (SPR) assay showed that the affinity for ENO1 was stronger (KD = 2.5 µM) for the resulting cell-targeting drug, DOX-P, than for DOX. Moreover, DOX-P exhibited acid-responsive capabilities, enabling precise release at the tumor site under the guidance of the homing peptide and alleviating DOX-induced cardiotoxicity. An efficacy experiment confirmed that, the targeting ability of DOX-P toward ENO1 demonstrated superior antitumor activity against colorectal cancer than that of DOX, while reducing its toxicity to cardiomyocytes. Furthermore, in vivo metabolic distribution results indicated low accumulation of DOX-P in nontumor sites, further validating its targeting ability. These results showed that the ENO1-targeted DOX-P peptide has great potential for application in targeted drug-delivery systems for colorectal cancer therapy.

Multiphase Flow Hemodynamic Evaluation of Vertebral Artery Stenosis Lesions and Plaque Stability.

BACKGROUND: Atherosclerosis is one of the main causes of vertebral artery stenosis, which reduces blood supply to the posterior circulation, resulting in cerebral infarction or death. OBJECTIVE: To investigate stenosis rates and locations on the development of vertebral artery plaques. METHODS: Stenosis models with varying degrees and positions of stenosis were established. The stenosis area was comprehensively analyzed using multiphase flow numerical simulation. Wall shear stress (WSS), blood flow velocity, and red blood cell (RBC) volume fraction were calculated. RESULTS: Blood flow velocity in 30-70% stenosis of each segment tended to increase significantly higher than normal. Downstream of 50% stenosis exhibited turbulent flow; downstream of 70% displayed reflux. Severe stenosis increases the WSS and distribution area. The mixed area of high and low WSS appeared downstream of the stenosis. The RBC volume fraction at the stenosis increased (maximum value: 0.487 at 70% stenosis in the V4), which was 1.08 times the normal volume fraction. Turbulent and backflow regions exhibited complex RBC volume fraction distributions. CONCLUSION: Flow velocity, WSS, and RBC volume fraction at the stenosis increase with stenosis severity, increasing plaque shedding. Narrow downstream spoiler and reflux areas possess low WSS and high erythrocyte volume fractions, accelerating plaque growth.

Comparison of biomechanical parameters of two Chinese cervical spine rotation manipulations based on motion capture and finite element analysis.

Objective: The purpose of this study was to obtain the stress-strain of the cervical spine structure during the simulated manipulation of the oblique pulling manipulation and the cervical rotation-traction manipulation in order to compare the mechanical mechanism of the two manipulations. Methods: A motion capture system was used to record the key kinematic parameters of operating the two manipulations. At the same time, a three-dimensional finite element model of the C0-T1 full healthy cervical spine was established, and the key kinematic parameters were loaded onto the finite element model in steps to analyze and simulate the detailed process of the operation of the two manipulations. Results: A detailed finite element model of the whole cervical spine including spinal nerve roots was established, and the validity of this 3D finite element model was verified. During the stepwise simulation of the two cervical spine rotation manipulations to the right, the disc (including the annulus fibrosus and nucleus pulposus) and facet joints stresses and displacements were greater in the oblique pulling manipulation group than in the cervical rotation-traction manipulation group, while the spinal cord and nerve root stresses were greater in the cervical rotation-traction manipulation group than in the oblique pulling manipulation group. The spinal cord and nerve root stresses in the cervical rotation-traction manipulation group were mainly concentrated in the C4/5 and C5/6 segments. Conclusion: The oblique pulling manipulation may be more appropriate for the treatment of cervical spondylotic radiculopathy, while cervical rotation-traction manipulation is more appropriate for the treatment of cervical spondylosis of cervical type. Clinicians should select cervical rotation manipulations for different types of cervical spondylosis according to the patient's symptoms and needs.

Analysis of Transient Response of ZPW-2000A Jointless Track Circuit Considering Frequency Variation.

In order to accurately analyze the influence of electromagnetic transient signals on the jointless track circuit when the electromagnetic transient signal propagates in the rail, it is necessary to consider the frequency-variable load terminated in the ZPW-2000A jointless track circuit and the frequency-variable loss inside the rail. A method is proposed for calculating the transient response of transmission lines system with frequency-variable end load of jointless track circuit. Firstly, the transmission lines model of jointless track circuit is established, based on multiconductor transmission lines theory, the model equation is deduced and discretized by finite difference time domain (FDTD). The vector fitting method is used to express the admittance of the tuning region in the track circuit, and the rational approximation function of the tuning region is derived from the poles, residues, and constants. The voltage and current at nodes in the tuning region are calculated by piecewise linear recursive convolution algorithm. Combined with the discrete transmission line equation, the current and voltage expression of the transient electromagnetic signal at the receiving end of the track circuit in time domain is obtained. Compared with state variable method, the error is less than 6%, which verifies the correctness of the proposed method. Finally, this paper studies the influence laws of different factors on the overvoltage at the receiving end of jointless track circuit and the weak links of jointless track circuit under the influence of transient electromagnetic signal. It provides theoretical reference for fault research and anti-interference analysis of ZPW-2000A jointless track circuit.

Design of IoT Gateway for Crop Growth Environmental Monitoring Based on Edge-Computing Technology.

With the extensive use of the Internet of Things (IoT) in agriculture, the number of terminals are also grow rapidly. This will increase the network traffic and computing pressure of the centralized server. The centralized data processing mode used in traditional agriculture cannot meet the needs of the Internet of everything era. This paper designs a gateway based on edge-computing technology for monitoring crop growth environment. It uses virtualized container technology to package long-range wide-area network (LoRaWAN) server, pest identification, and environmental information data fusion functions into images. It forms integrated operation mode of multiple function in agriculture. The gateway applies message-oriented middleware to standardize and customize the data transmission among functional modules, clouds, and edges. Through simulation and field test, the designed gateway can achieve the functions of each module at the same time, the resource utilization, and the transmission quality are stable. The edge-computing gateway has the advantages of low cost, low latency, and low power consumption which has practical significance.

Ultrasound Guidance Enhances the Efficiency of Brachial Plexus Block and Ameliorates the Vascular Injury Compared with Nerve Stimulator Guidance in Hand Surgery Patients.

Background: Nerve stimulation guidance and ultrasound guidance are two major methods that have been widely accepted and applied in axillary brachial plexus block. However, the differences between the effects of these two types of guidance still need to be further elucidated for clinical usage. Materials and Methods: Overall, 208 patients undergoing elective upper limb surgeries and receiving axillary brachial plexus block were recruited in our study. The patients were randomly assigned to receive either ultrasound guidance (group U, n = 112) or nerve stimulation (group N, n = 96). Pinprick test was performed for assessing the sensory blockades. The pain was evaluated by visual analog scale (VAS). Reactive oxygen species (ROS) levels were measured by dichloro-dihydro-fluorescein diacetate staining and serum levels of nitric oxide (NO), nitric oxide synthases (NOS), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein 1 (MCP1) were evaluated by ELISA. Results: Ultrasound guidance significantly enhanced the quality of the sensory blockade and reduced the VAS scores when compared with the nerve stimulator guidance. In addition, the production of ROS, NO, NOS, TNF-α, and MCP-1 were significantly alleviated by ultrasound guidance. Conclusion: Ultrasound-guided brachial plexus block relieves pain during operation, provides higher success rates in the nerve block, causes less vascular damage and results in lower levels of inflammatory cytokines secretion when compared with neurostimulator-directed brachial plexus blockage.

Upregulation of circular RNA circ_0001721 predicts unfavorable prognosis in osteosarcoma and facilitates cell progression via sponging miR-569 and miR-599.

Osteosarcoma (OS) is the most frequent bone malignancy in human. Growing evidence suggests that circular RNAs (circRNAs) play a significant role in regulating tumorigenesis and progression. Previously, circ_0001721 was identified upregulated in OS tissues screened by circRNA microarrays. In the current study, circ_0001721 expression in OS tissue samples and cells were measured by qRT-PCR. Its clinical value was also explored. For the part of functional assays, CCK-8, clone-forming, flow cytometric, Transwell, xenograft assays were performed. Dual luciferase reporter assays were used to examine the mechanism of circ_0001721. We found that circ_0001721 was enhanced in OS tissue samples and cell lines and the overexpression of circ_0001721 is closely related to clinical severity. In addition, circ_0001721 may be used as a prognostic indicator for OS patients. What's more, loss-of-function and gain-of-function assays demonstrated circ_0001721 facilitates cell progression in OS. Circ_0001721 could sponge miR-569 and miR-599. The oncogenic properties of circ_0001721 is partly attributed to its repression on miR-569 and miR-599. Collectively, the present data reveal the participation of circ_0001721 in tumorigenesis of OS cells, and may indicate a novel therapeutic target.

Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1.

Bone metastasis of breast cancer makes patients suffer from pain, fractures, spinal cord compression, and hypercalcemia, and is almost incurable. Although the mechanisms of bone metastasis in breast cancers have been studied intensively, novel specific target will be helpful to the development of new therapeutic strategy of breast cancer. Herein, we focused on the microRNA of tumor cell-derived exosomes to investigate the communication between the bone microenvironment and tumor cells. The expression of miR-20a-5p in the primary murine bone marrow macrophages (BMMs), MCF-10A, MCF-7, and MDA-MB-231 cell lines, as well as the cell-derived exosomes were assessed by qRT-PCR. Transwell assays were used to evaluate the effects of miR-20a-5p on tumor cell migration and invasion. The expression of exosomes marker including CD63and TSG101 was detected by Western Blot. Cell cycle distribution of BMMs was analyzed by flow cytometry. 3-UTR luciferase reporter assays were used to validate the putative binding between miR-20a-5p and SRCIN1. MiR-20a-5p was highly expressed in breast tumor tissues and the exosomes of MDA-MB-231 cells. MiR-20a-5p promoted migration and invasion in MDA-MB-231 cells, and the proliferation and differentiation of osteoclasts. MDA-MB-231 cell-derived exosomes transferred miR-20a-5p to BMMs and facilitated the osteoclastogenesis via targeting SRCIN1. The present work provides evidence that miR-20a-5p transferred from breast cancer cell-derived exosomes promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1, providing scientific foundations for the development of exosome or miR-20a-5p targeted therapeutic intervention in breast cancer progression.

Evaluation of different b-values in DWI and 1H MRS for pancreatic cancer and pancreatitis: a rabbit model.

Pancreatic cancer is a common malignant tumor with high incidence of metastasis. Currently, there is no absolute standard for the choice of b-value for diffusion-weighted imaging (DWI) for pancreatic cancer. The b-value is rarely reported in animal model study, especially in pancreatic cancer/mass pancreatitis rabbit models. The authors' aim was to determine the different b-values to differentiate the diagnosis of pancreatic cancer and mass pancreatitis in rabbit models using DWI. When comparing the effect of different b-values in diagnostic process, the pathological results could be regarded as the gold standard. In this research, 30 healthy New Zealand rabbits were selected and divided into three groups by random number table method: group 1 (pancreatic cancer), group 2 (mass pancreatitis) and the control group (healthy). After DWI (three different b-values 333, 667, 1000 s/mm2, respectively) and MRI examination, the model rabbits were then killed. Afterward, the tumor mass was removed for biopsy, and occupation anatomy and tumor histopathology were examined. Fat-suppressing sequences of T2WI, DWI, ADC, difference of ADC (DADC), and MRS were used. The present study determined that the effective differential diagnosis of pancreatic cancer and pancreatitis was determined at low b-values (333 s/mm2) when performed DWI inspection in rabbit models.