Distance-based paper analytical devices integrated with molecular imprinted polymers for Escherichia coli quantification.

The development of distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) to monitor Escherichia coli (E. coli) levels in food samples is presented. The fluidic workflow on the device is controlled using a designed hydrophilic bridge valve. Dopamine serves as a monomer for the formation of the E. coli-selective MIP layer on the dPADs. The detection principle relies on the inhibition of the E. coli toward copper (II) (Cu2+)-triggered oxidation of o-phenylenediamine (OPD) on the paper substrate. Quantitative detection is simply determined through visual observation of the residual yellow color of the OPD in the detection zone, which is proportional to E. coli concentration. The sensing exhibits a linear range from 25.0 to 1200.0 CFU mL-1 (R2 = 0.9992) and a detection limit (LOD) of 25.0 CFU mL-1 for E. coli detection. Additionally, the technique is highly selective with no interference even from the molecules that have shown to react with OPD to form oxidized OPD. The developed device demonstrates accuracy and precision for E. coli quantification in food samples with recovery percentages between 98.3 and 104.7% and the highest relative standard deviation (RSD) of 4.55%. T-test validation shows no significant difference in E. coli concentration measured between our method and a commercial assay. The proposed dPAD sensor has the potential for selective and affordable E. coli determination  in food samples without requiring sample preparation. Furthermore, this strategy can be extended to monitor other molecules for which MIP can be developed and integrated into paper-microfluidic platform.

Simple distance-based thread analytical device integrated with ion imprinted polymer for Zn2+ quantification in human urine samples.

This article presents the development of a distance-based thread analytical device (dTAD) integrated with an ion-imprinted polymer (IIP) for quantitative monitoring of zinc ions (Zn2+) in human urine samples. The IIP was easily chemically modified onto the thread channel using dithizone (DTZ) as a ligand to bind to Zn2+ with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as well as 2,2-azobisisobutyronitrile (AIBN) as cross-linking agents to enhance the selectivity for Zn2+ detection. The imprinted polymer was characterized using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDS). Under optimization, the linear detection range was from 1.0 to 20.0 mg L-1 (R2 = 0.9992) with a limit of detection (LOD) of 1.0 mg L-1. Other potentially interfering metal ions and molecules did not interfere with this approach, leading to high selectivity. Furthermore, our technique exhibits a remarkable recovery ranging from 100.48% to 103.16%, with the highest relative standard deviation (% RSD) of 5.44% for monitoring Zn2+ in human control urine samples, indicating high accuracy and precision. Similarly, there is no significant statistical difference between the results obtained using our method and standards on zinc supplement sample labels. The proposed method offers several advantages in detecting trace Zn2+ for point-of-care (POC) medical diagnostics and environmental sample analysis, such as ease of use, instrument-free readout, and cost efficiency. Overall, our developed dTAD-based IIP method holds potential for simple, affordable, and rapid detection of Zn2+ levels and can be applied to other metal ions' analysis.

Distance-based paper analytical device for multiplexed quantification of cytokine biomarkers using carbon dots integrated with molecularly imprinted polymer.

This article introduces distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) and carbon dots (CDs) for simultaneous quantification of cytokine biomarkers, namely C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in human biological samples for diagnosis of cytokine syndrome. Using fluorescent CDs and MIP technology, the dPAD exhibits high selectivity and sensitivity. Detection is based on fluorescence quenching of CDs achieved through the interaction of the target analytes with the MIP layer on the paper substrate. Quantitative analysis is easily accomplished by measuring the distance length of quenched fluorescence with a traditional ruler and naked eye readout enabling rapid diagnosis of cytokine syndrome and the underlying infection. Our sensor demonstrated linear ranges of 2.50-24.0 pg mL-1 (R2 = 0.9974), 0.25-3.20 pg mL-1 (R2 = 0.9985), and 1.50-16.0 pg mL-1 (R2 = 0.9966) with detection limits (LODs) of 2.50, 0.25, and 1.50 pg mL-1 for CRP, TNF-α, and IL-6, respectively. This sensor also demonstrated remarkable selectivity compared to a sensor employing a non-imprinted polymer (NIP), and precision with the highest relative standard deviation (RSD) of 5.14%. The sensor is more accessible compared to prior methods relying on expensive reagents and instruments and complex fabrication methods. Furthermore, the assay provided notable accuracy for monitoring these biomarkers in various human samples with recovery percentages ranging between 99.22% and 103.58%. By integrating microfluidic systems, nanosensing, and MIPs technology, our developed dPADs hold significant potential as a cost-effective and user-friendly analytical method for point-of-care diagnostics (POC) of cytokine-related disorders. This concept can be further extended to developing diagnostic devices for other biomarkers.

Outcomes of post-implantation syndrome after endovascular repair for Stanford type B aortic dissection.

OBJECTIVE: The aim of this study was to investigate the correlation between post-implantation syndrome (PIS) and long-term prognosis in patients with Stanford type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). METHODS: This retrospective study included 547 consecutive patients diagnosed with TBAD who underwent TEVAR at our institution between January 2014 and December 2019. Patients were categorized into two groups: the PIS group (patients with post-TEVAR PIS) and the non-PIS group (patients without post-TEVAR PIS). In-hospital and follow-up data were analyzed. RESULTS: The incidence of PIS was 28.9% (158/547 patients). No baseline differences were observed between the PIS (n = 158) and the non-PIS (n = 389) groups. The proportion of emergency surgery in the PIS group was higher than that in the non-PIS group (44.9% vs 26.0%; P < .001), the operation time was longer (median, 65.0; interquartile range [IQR], 56.0-75.0 minutes vs 56.0; IQR, 45.0-66.0 minutes; P < .001), the volume of contrast medium used (median, 65.0; IQR, 56.0-75.0 mL vs 56.0; IQR, 45.0-66.0 mL; P < .001), and the average number of trunk stents (1.85 ± 0.4 vs 1.34 ± 0.5 pieces; P < .001) and branch stents (0.7 ± 0.7 vs 0.2 ± 0.5 pieces; P < .001) used were more in the PIS group than in the non-PIS group. The incidence of supra-aortic branch procedures was higher in the PIS group than in the non-PIS group. There was no significant difference in device-related complications (DRCs) or 30-day mortality between the two groups (2.5% vs 4.4%; P = .442 and 1.3% vs 1.3%; P = .688, respectively). Univariate and multivariable logistic regression analysis showed that emergency surgery, number of trunk stents >1, operation time >58.5 minutes, and contrast medium volume >75 mL were risk factors for PIS, and the odds ratios of emergency operation, number of trunk stents >1 piece, operation time >58.5 minutes, and contrast medium volume >75 mL were 2.526 (95% confidence interval [CI], 1.530-4.173), 4.651 (95% CI, 2.838-7.624), 3.577 (95% CI, 2.201-5.815), and 7.356 (95% CI, 4.111-13.160), respectively. Follow-up was completed in 98.5% (532/540) of the patients, with a median follow-up of 67 months (IQR, 50-86 months). There was no significant difference in survival between the PIS and non-PIS groups (12.4% vs 10.3%; P = .476) during follow-up. The incidences of DRCs (7.8% vs 11.6%; P = .200) and aortic false lumen thrombosis (75.8% vs 79.2%; P = .399) were comparable between the PIS and non-PIS groups. Univariate logistic regression analysis showed that PIS had no effect on long-term follow-up mortality, DRCs, entry flow, or aortic false lumen thrombosis rate. CONCLUSIONS: PIS is relatively common after TEVAR and emergency surgery; number of trunk stents >1, operation time >58.5 minutes, and contrast medium volume >75 mL are of high predictive value for the assessment of PIS after TEVAR. However, PIS had little effect on early and late postoperative mortality or DRCs.

Highly Sensitive Photothermal Microfluidic Thread-Based Duplex Immunosensor for Point-of-Care Monitoring.

Herein, we successfully developed a thread-based analytical device (µTAD) for simultaneous immunosensing of two biomolecules with attomolar sensitivity by using a photothermal effect. A photothermal effect exploits a strong light-to-heat energy conversion of plasmonic metallic nanoparticles at localized surface plasmon resonance. The key innovation is to utilize the cotton thread to realize this sensor and the use of chitosan modification for enhancing the microfluidic properties, for improving the efficiency of photothermal conversion, and for sensor stability. The developed µTAD sensor consists of (i) a sample zone, (ii) a conjugation zone coated with gold nanoparticles bound with an antibody (AuNPs-Ab2), and (iii) a test zone immobilized with a capture antibody (anti-Ab1). The prepared µTAD is assembled in a custom three-dimensional (3D) printed device which holds the laser for illumination and the thermometer for readout. The 3D-printed supportive device enhances signal response by focusing light and localizing the heat generated. For proof of concept, simultaneous sensing of two key stress and inflammation biomarkers, namely, cortisol and interleukin-6 (IL-6), are monitored using this technique. Under optimization, this device exhibited a detection linear range of 2.0-14.0 ag/mL (R2 = 0.9988) and 30.0-360.0 fg/mL (R2 = 0.9942) with a detection limit (LOD) of 1.40 ag/mL (∼3.86 amol/L) and 20.0 fg/mL (∼950.0 amol/L) for cortisol and IL-6, respectively. Furthermore, the analysis of both biomolecules in human samples indicated recoveries in the range of 98.8%-102.88% with the highest relative standard deviation being 3.49%, offering great accuracy and precision. These results are the highest reported sensitivity for these analytes using an immunoassay method. Our PT-µTAD strategy is therefore a promising approach for detecting biomolecules in resource-limited point-of-care settings.

Tunable Radio Frequency Antenna Based on Phase Change Materials.

In conventional communication systems, dedicated tunable circuit elements are used to realize different functions and achieve performance metrics. For example, tuning the center frequency or the input impedance of an antenna in a radio frequency (RF) system is performed by complex impedance-matching circuits. In this paper, the antenna utilizes the temperature-induced irreversible mechanical deformation of a shape memory alloy (SMA) as a natural way to tune the antenna's shape and configuration, thereby providing inherent tunability without bulky circuit elements. This paradigm of material programming for impedance tuning of an SMA-based antenna is validated by both numerical simulation and measurements.

Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling.

Breathing is a singularly robust behavior, yet this motor pattern is continuously modulated at slow and fast timescales to maintain blood-gas homeostasis, while intercalating orofacial behaviors. This functional multiplexing goes beyond the rhythmogenic function that is typically ascribed to medullary respiration-modulated networks and may explain lack of progress in identifying the mechanism and constituents of the respiratory rhythm generator. By recording optically along the ventral respiratory column in medulla, we found convergent evidence that rhythmogenic function is distributed over a dispersed and heterogeneous network that is synchronized by electrotonic coupling across a neuronal syncytium. First, high-speed recordings revealed that inspiratory onset occurred synchronously along the column and did not emanate from a rhythmogenic core. Second, following synaptic isolation, synchronized stationary rhythmic activity was detected along the column. This activity was attenuated following gap junction blockade and was silenced by tetrodotoxin. The layering of syncytial and synaptic coupling complicates identification of rhythmogenic mechanism, while enabling functional multiplexing.

Temperature Sensing Shape Morphing Antenna (ShMoA).

Devices that can morph their functions on demand provide a rich yet unexplored paradigm for the next generation of electronic devices and sensors. For example, an antenna that can morph its shape can be used to adapt communication to different wireless standards or improve wireless signal reception. We utilize temperature-sensitive shape memory alloys (SMA) to realize a shape morphing antenna (ShMoA). In the designed architecture, multiple conjoined shape memory alloy sections form the antenna. The shape morphing of this antenna is achieved through temperature control. Different temperature threshold levels are used for programming the shape. Besides its conventional use for RF applications, ShMoA can serve as a multi-level temperature sensor, analogous to thermoreceptors in an insect antenna. ShMoA essentially combines the function of temperature sensing, embedded computing for detection of threshold crossings, and radio frequency readout, all in the single construct of a shape-morphing antenna (ShMoA) without the need for any battery or peripheral electronics. The ShMoA can be employed as bio-inspired wireless temperature sensing antennae on mobile robotic flies, insects, drones and other robots. It can also be deployed as programmable antennas for multi-standard wireless communication.

Recent progress in electrospun nanomaterials for wearables.

Wearables have garnered significant attention in recent years not only as consumer electronics for entertainment, communications, and commerce but also for real-time continuous health monitoring. This has been spurred by advances in flexible sensors, transistors, energy storage, and harvesting devices to replace the traditional, bulky, and rigid electronic devices. However, engineering smart wearables that can seamlessly integrate with the human body is a daunting task. Some of the key material attributes that are challenging to meet are skin conformability, breathability, and biocompatibility while providing tunability of its mechanical, electrical, and chemical properties. Electrospinning has emerged as a versatile platform that can potentially address these challenges by fabricating nanofibers with tunable properties from a polymer base. In this article, we review advances in wearable electronic devices and systems that are developed using electrospinning. We cover various applications in multiple fields including healthcare, biomedicine, and energy. We review the ability to tune the electrical, physiochemical, and mechanical properties of the nanofibers underlying these applications and illustrate strategies that enable integration of these nanofibers with human skin.

A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and Its Disruptive Application.

Background: Previous studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the fovea centralis in the human retina. This study aimed to develop and explore the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea. Methods: Tree shrews were clinically and pathologically evaluated for the development and characteristics of EAU immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs). IRBP-specific T-cell proliferation and serum cytokine of tree shrews were evaluated to determine the immune responses. Differentially expressed genes (DEGs) were identified in the eyes of tree shrews with EAU by RNA-sequencing. The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU. Results: IRBP1197-1211 and R14 successfully induced chronic EAU with subretinal deposits and retinal damage in the tree shrews. The immunological characteristics presented the predominant infiltration of microglia/macrophages, dendritic cells, and CD4-T-cells into the uvea and retina and pathogenic T helper (Th) 1 and Th17 responses. The subretinal deposits positively expressed amyloid ß-protein (Aß), CD8, and P2Y purinoceptor 12 (P2RY12). The crucial DEGs in R14-induced EAU, such as P2RY2 and adenylate cyclase 4 (ADCY4), were enriched for several pathways, including inflammatory mediator regulation of transient receptor potential (TRP) channels. The upregulated RGS4 in IRBP-induced EAU was associated with mitogen-activated protein kinase (MAPK) activity. RGS4 inhibition and dihydroartemisinin could significantly alleviate the retinal pathological injuries of IRBP1197-1211-induced EAU by decreasing the expression of CD4 T-cells. Conclusion: Our study provides a novel chronic EAU in tree shrews elicited by bovine R14 and tree shrew IRBP1197-1211 characterized by retinal degeneration, retinal damage with subretinal Aß deposits and microglia/macrophage infiltration, and T-cell response, probably by altering important pathways and genes related to bacterial invasion, inflammatory pain, microglial phagocytosis, and lipid and glucose metabolism. The findings advance the knowledge of the pathogenesis and therapeutics of the fovea-involved visual disturbance in human uveitis.

Perinatal methadone exposure attenuates myelination and induces oligodendrocyte apoptosis in neonatal rat brain.

Methadone (MTD) is a commonly prescribed treatment for opioid use disorder in pregnancy, despite limited information on the effects of passive exposure on fetal brain development. Animal studies suggest a link between perinatal MTD exposure and impaired white matter development. In this study, we characterized the effect of perinatal MTD exposure through the evaluation of oligodendrocyte development and glial cell activation in the neonatal rat brain. Six pregnant Sprague Dawley rat dams were randomized to MTD (0.2 mL/L) or untreated drinking water from embryonic day 7. Pups were terminated at postnatal day 7 and tissue sections were harvested from six randomly selected pups (one male and one female per litter) of each experimental group for immunohistochemistry in areas of corpus callosum (CC), lateral CC, external capsule (EC), and cerebellar white matter. In the MTD-exposed rat pups, myelination was significantly decreased in the CC, lateral CC, EC, and arbor vitae compared with the controls. The increased density and percentage of oligodendrocyte precursor cells (OPCs) were observed in the CC and cerebellar white matter. The highly active proliferation of OPCs as well as decreased density and percentage of differentiated oligodendrocytes were found in the cerebellum but no differences in the cerebrum. Apoptotic activities of both differentiated oligodendrocytes and myelinating oligodendrocytes were significantly increased in all regions of the cerebrum and cerebellum after MTD exposure. There was no quantitative difference in astrocyte, however, cell density and/or morphologic difference consistent with activation were observed in microglia throughout MTD-exposed CC and cerebellum. Taken together, perinatal MTD exposure reveals global attenuation of myelination, accelerated apoptosis of both differentiated and myelinating oligodendrocytes, and microglia activation, supporting an association between antenatal MTD exposure and impaired myelination in the developing brain.

Hard polymeric porous microneedles on stretchable substrate for transdermal drug delivery.

Microneedles offer a convenient transdermal delivery route with potential for long term sustained release of drugs. However current microneedle technologies may not have the mechanical properties for reliable and stable penetration (e.g. hydrogel microneedles). Moreover, it is also challenging to realize microneedle arrays with large size and high flexibility. There is also an inherent upper limit to the amount and kind of drugs that can be loaded in the microneedles. In this paper, we present a new class of polymeric porous microneedles made from biocompatible and photo-curable resin that address these challenges. The microneedles are unique in their ability to load solid drug formulation in concentrated form. We demonstrate the loading and release of solid formulation of anesthetic and non-steroidal anti-inflammatory drugs, namely Lidocaine and Ibuprofen. Paper also demonstrates realization of large area (6 × 20 cm2) flexible and stretchable microneedle patches capable of drug delivery on any body part. Penetration studies were performed in an ex vivo porcine model supplemented through rigorous compression tests to ensure the robustness and rigidity of the microneedles. Detailed release profiles of the microneedle patches were shown in an in vitro skin model. Results show promise for large area transdermal delivery of solid drug formulations using these porous microneedles.

Microfluidic-based fabrication and characterization of drug-loaded PLGA magnetic microspheres with tunable shell thickness.

To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 µm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.

Dynamic glial response and crosstalk in demyelination-remyelination and neurodegeneration processes.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system. It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes. Glial cells (microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis. Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process. A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration. This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models. In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell- and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

AKT/GSK-3ß/ß-catenin signaling pathway participates in erythropoietin-promoted glioma proliferation.

PURPOSE: Although erythropoietin (EPO) has been proven to significantly promote the proliferation of cancer cells, the mechanism for promoting glioma proliferation is poorly understood. Here, we examined the functional role of the AKT/GSK-3ß/ß-catenin signaling pathway in the EPO-mediated proliferation of glioma. METHODS: The distribution of EPO and Ki-67 among clinical samples with different WHO grades was plotted by Immunological Histological Chemistry analysis. U87 and U251 glioma cell lines were treated with short hairpin RNA targeting (shEPO), recombinant human erythropoietin (rhEPO) and/or AKT-specific inhibitor (MK-2206). The changes in phosphorylated AKT, nuclear ß-catenin, cyclin D1 and p27kip1 expression were detected. Cell cycle distributions and glioma proliferation in vitro and in vivo were analyzed. RESULTS: The expression level of EPO was significantly elevated with the increase of WHO grade and Ki67 in clinical glioma specimens. In vitro, knockdown of endogenous EPO in U87 and U251 cells effectively block the phosphorylation of AKT and GSK-3ß and the expression of nuclear ß-catenin. shEPO treatment also significantly decreased the expression of cyclin D1 and increased the expression of p27kip1. The cell cycle transition then slowed down and the proliferation of glioma cells or mouse xenograft tumors both decreased. Treatment of cells or tumors with extra rhEPO reversed the above biological effects mediated by shEPO. rhEPO-induced activation of the AKT/GSK-3ß/ß-catenin pathway and proliferation were abolished by MK-2206. CONCLUSIONS: Our study identified the AKT/GSK-3ß/ß-catenin axis as a critical mediator of EPO-induced glioma proliferation and further provided a clinically significant dimension to the biology of EPO.

Parental Uveitis Influences Offspring With an Increased Susceptibility to the Experimental Autoimmune Uveitis.

Purpose: Previous studies have shown that parental abnormal physiological conditions such as inflammation, stress, and obesity can be transferred to offspring. The purpose of this study was to investigate the impact of parental uveitis on the development and susceptibility to experimental autoimmune uveitis (EAU) in offspring. Methods: Parental male and female B10RIII mice were immunized with interphotoreceptor retinoid binding protein (IRBP) 161-180 in complete Freund's adjuvant and were immediately allowed to mate. Gross examination of the offspring gestated with EAU was performed to determine the influence of parental uveitis on offspring development after birth. Gene expression profiles were analyzed in the affected eyes of offspring under EAU to identify differentially expressed genes (DEGs). Adult offspring were given 5, 25, and 50 µg IRBP161-180 to compare their susceptibility to EAU. Immunized mice were clinically and pathologically evaluated for the development of EAU. Ag-specific T-cell proliferation and IL-17 production from spleens and lymph nodes were evaluated on day 14 or 35 after immunization. Results: Hair loss, delay of eye opening, and swollen spleens in the offspring from parents with uveitis were observed from day 14 to 39 after birth. DEGs were involved in the immune system process, muscle system process, and cell development. The altered antigen processing and presentation, cell adhesion molecules, and phagosome in the eyes of the offspring from uveitis-affected parents were enriched. Offspring gestated with EAU showed a susceptibility to EAU and an earlier onset and higher severity of EAU compared to the control group mice. IRBP-specific lymphocyte proliferation and IL-17 production were observed in the EAU offspring with exposure to parental uveitis. Conclusions: The results suggest that mouse parents with uveitis can increase their offspring's susceptibility to EAU, probably through altering cell adhesion molecules and antigen processing and presentation related to the T-cell proliferation and Th17 response.

Patient-derived xenografts of different grade gliomas retain the heterogeneous histological and genetic features of human gliomas.

BACKGROUND: Gliomas account for the major part of primary brain tumors. Based on their histology and molecular alternations, adult gliomas have been classified into four grades, each with distinct biology and outcome. Previous studies have focused on cell-line-based models and patient-derived xenografts (PDXs) from patient-derived glioma cultures for grade IV glioblastoma. However, the PDX of lower grade diffuse gliomas, particularly those harboring the endogenous IDH mutation, are scarce due to the difficulty growing glioma cells in vitro and in vivo. The purpose of this study was to develop a panel of patient-derived subcutaneous xenografts of different grade gliomas that represented the heterogeneous histopathologic and genetic features of human gliomas. METHODS: Tumor pieces from surgical specimens were subcutaneously implanted into flanks of NOD-Prkdcscid ll2rgnull mice. Then, we analyzed the association between the success rate of implantation with clinical parameters using the Chi square test and resemblance to the patient's original tumor using immunohistochemistry, immunofluorescence, short tandem repeat analysis, quantitative real-time polymerase chain reaction, and whole-exome sequencing. RESULTS: A total of 11 subcutaneous xenografts were successfully established from 16 surgical specimens. An increased success rate of implantation in gliomas with wild type isocitrate dehydrogenase (IDH) and high Ki67 expression was observed compared to gliomas with mutant IDH and low Ki67 expression. Recurrent and distant aggressive xenografts were present near the primary implanted tumor fragments from WHO grades II to IV. The xenografts histologically represented the corresponding patient tumor and reconstituted the heterogeneity of different grade gliomas. However, increased Ki67 expression was found in propagated xenografts. Endothelial cells from mice in patient-derived xenografts over several generations replaced the corresponding human tumor blood vessels. Short tandem repeat and whole-exome sequencing analyses indicated that the glioma PDX tumors maintained their genomic features during engraftments over several generations. CONCLUSIONS: The panel of patient-derived glioma xenografts in this study reproduced the diverse heterogeneity of different grade gliomas, thereby allowing the study of the growth characteristics of various glioma types and the identification of tumor-specific molecular markers, which has applications in drug discovery and patient-tailored therapy.

Combination of microfluidic chip and electrostatic atomization for the preparation of drug-loaded core-shell nanoparticles.

To overcome the shortcoming of drug-loaded nanoparticles, such as high initial burst release and wide size distribution, a novel manufacturing technique for core-shell structure nanoparticle was developed by combining microfluidic chip and electrohydrodynamic atomization. In this study, the mixture solution of the surfactant 1, 2- dipalmitoyl-sn-glycero-3-phosphoglycerol and the polymeric coating material polylactic-glycolic-acid was introduced into the outer microchannel of the microfluidic chip as the particle's shell. And the encapsulated drug paclitaxel was pumped into the inner microchannel as the core. Then, the particles with a nanoscale-size core-shell structure were generated by applying an electric field on the laminar flow which was formed in the microfluidic chip. Operation parameters, including working voltage, carrier material and surfactant concentration as well as liquid flow rates were optimized for nanoparticles generation. The properties of drug-loaded nanoparticles in terms of their particle size, zeta potential and encapsulation efficiency were investigated. Under the optimal experimental conditions, the particle size was approximately 145 nm and encapsulation efficiency reached 92%. Moreover, the drug release of these nanoparticles could be prolonged over a significant period for more than ten days. It can be expected that this innovative approach could provide a useful platform for drug-loaded core-shell nanoparticles developing.

Peri-operative risk factors for in-hospital mortality in acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection (TAAD) is cardiovascular emergency and requires surgical interventions. In-hospital mortality rate of surgical-treated TAAD patients remains high. We aim to examine the prognostic implications of peri-operative parameters to identify high-risk patient for in-hospital mortality. METHODS: A total of 264 surgically treated TAAD patients were included in this study. The association between in-hospital mortality and peri-operative parameters were examined. RESULTS: Thirty patients (11.36%) died during hospitalization. Patients with higher Apache II score had a significantly higher rate of in-hospital mortality when compared with patients scored ≤20 in unadjusted model [Score 21-25: HR =12.9 (1.7-100.8), P=0.0148; Score >25: HR =94.5 (12.6-707.6), P<0.0001]. Patients with Sbp >120 mmHg, Cr >200 mmol/L (both at admission and after surgery), BUN >8.2 mmol/L (both at admission and after surgery), AST >80 µ/L, aortic cross-clamping time >120 min and cardiopulmonary bypass time (CPBT) >230 min were also significantly related to higher rate of in-hospital mortality in univariate analysis. In multivariable analysis, APACHE II score [Score 21-25: HR =9.5 (1.2-74.4), P=0.032; Score >25: HR =51.0 (6.7-387.7), P=0.0001], AST >80 µmol/L [HR =2.3 (1.1-4.8), P=0.0251], aortic cross-clamping time >120 min (HR =2.9 (1.1-7.7), P=0.0315) remained significant in predicting TAAD in-hospital mortality. CONCLUSIONS: APACHE II score could be a useful tool to predict TAAD in-hospital mortality. AST >80 µ/L and aortic cross-clamping time >120 min were also independent predictors.