Double-Network MK Resin-Modified Silica Aerogels for High-Temperature Thermal Insulation.

Polymer-reinforced SiO2 aerogel materials exhibit excellent thermal insulation, flame resistance, and mechanical properties; however, the poor thermal stability of organic components limits their application in high-temperature environments. Herein, a double-network MK/SiO2 aerogel was synthesized by direct copolymerization of a methyl-containing silicone resin (MK) and tetraethoxysilane (TEOS) under the cross-coupling of (3-aminopropyl) triethoxysilane (APTES) followed by an atmospheric drying method. The resulting MK/SiO2 aerogel, presenting a double-cross-linked MK and SiO2 network, shows a low density of 0.18 g/cm3, a high specific surface area of 716.6 m2/g, and a low thermal conductivity of 0.030 W/(m K). Especifically, the compressive strength of the MK/SiO2 aerogel (up to 3.24 MPa) is an order of magnitude higher than that of the pristine SiO2 aerogel (0.39 MPa) due to the introduction of the strong MK network and enhanced neck connections of SiO2 nanoparticles. Furthermore, the mutually supportive network endows the MK/SiO2 aerogels with significant resistance to ablation and oxidation up to 1000 °C, showing a high residual rate (89%), a high specific surface area (235.2 m2/g), and structural stability after thermal treatment under air atmosphere. These superior mechanical and thermal properties of the MK/SiO2 aerogels lead to attractive practical applications in energy transportation, thermal insulation, or aviation.

Development of gene model combined with machine learning technology to predict for advanced atherosclerotic plaques.

BACKGROUND: Atherosclerosis, as a major cause of stroke, is responsible for a quarter of deaths worldwide. In particular, rupture of late-stage plaques in large vessels such as the carotid artery can lead to serious cardiovascular disease. The aim of our study was to establish a genetic model combined with machining leaning techniques to screen out gene signatures and predict for advanced atherosclerosis plaques. METHODS: The microarray dataset GSE28829 and GSE43292 which were publicly obtained from the Gene Expression Omnibus database were utilized to screen for potential predictive genes. Differentially expressed genes (DEGs) were identified by using the "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses of these DEGs were performed by Metascape. Later, Random Forest (RF) algorithm was applied to further screen out top-30 genes which contribute the most. The expression data of top 30-DEGs were converted into a "Gene Score". Finally, we developed a model based on artificial neural network (ANN) to predict advanced atherosclerotic plaques. The model later was validated in an independent test dataset GSE104140. RESULTS: A total of 176 DEGs were identified in the training datasets. GO and KEGG enrichment analysis revealed that these genes were enriched in leukocyte-mediated immune response, cytokine- cytokine interactions, and immunoinflammatory signaling. Further, top-30 genes (including 25 upregulated and 5 downregulated DEGs) were screened as predictors by RF algorithm. The predictive model was developed with a significantly predictive value (AUC = 0.913) in the training datasets, and was validated with an independent dataset GSE104140 (AUC = 0.827). CONCLUSION: In present study, our prediction model was established and showed satisfactory predictive power in both training and test datasets. In addition, this is the first study adopted bioinformatics methods combined with machine learning techniques (RF and ANN) to explore and predict for the advanced atherosclerotic plaques. However, further investigations were needed to verify the screened DEGs and predictive effectiveness of this model.

In Situ Formation of the TiCN Phase in SiBCN Ceramic Aerogels Enabling Superior Thermal and Structural Stability up to 1800 °C.

Ceramic aerogels show excellent thermal insulation and functional performance for their unique nanoporous structure. However, conventional ceramic aerogels often undergo structural collapse and performance deterioration in high-temperature environments due to sintering, crystallization, and/or phase transition. Here, we designed a TiCN/SiBCN ceramic aerogel in which the TiCN phase was in situ formed through a carbothermal reaction during pyrolysis. Benefiting from its unique pearl-necklace-like structure, the TiCN/SiBCN aerogel exhibits a high specific surface area (248 m2/g), a low thermal conductivity (0.08 W/m·K), and a considerable compressive strength (2.2 MPa). The formation of a stable TiCN phase endows the aerogel with significant resistance to thermal decomposition and crystallization up to 1800 °C. Moreover, the TiCN/SiBCN aerogel retains high surface area and low thermal conductivity after thermal treatment, indicative of the stability and reliability of the nanoporous structure. The TiCN/SiBCN ceramic aerogel with superior thermal and structural stability is an ideal candidate for structural and functional applications in high-temperature environments.

Passive Filler-Loaded Silicon Oxycarbide Coating on Nickle Alloy with High Thermal Shocking Behavior and Oxidation Resistance.

Polymer-derived ceramic (PDC) coatings of considerable thickness can offer promising protection for metallic and superalloy substrates against oxidation and corrosion, yet the preparation remains challenging. Here, a SiOC/Al2O3/YSZ coating was prepared on a nickel alloy with a spraying method using Al2O3 and yttria-stabilized zirconia (YSZ) as passive fillers. The thickness can reach up to 97 µm with the optimal mass fraction and particle sizes of the passive fillers. A small or isolated SiOC phase is formed in the coating, which can effectively alleviate the shrinkage and cracking during the pyrolysis. The SiOC/Al2O3/YSZ coating exhibits low thermal conductivity and high bonding strength with the substrate. Moreover, the coating shows good thermal shock resistance between 800 °C-room temperature cycles and oxidation resistance at 1000 °C for 36 h. This work provides an effective guide for the design of thick PDC coatings to further promote their application in the thermal protective field.

The influence of unexpected early termination of intravenous rt-PA treatment on clinical outcome in acute ischemic stroke patients.

INTRODUCTION: This study aimed to explore the impact of unexpected early termination during intravenous thrombolysis on clinical prognosis in patients with acute ischemic stroke (AIS). METHODS: Patients who received intravenous thrombolysis were divided into an early termination group and a normal treatment group. The causes of unexpected termination were analyzed, and the prognosis was compared between the groups. RESULTS: The main causes of early termination of thrombolytic therapy included subjective wishes of family members (11.8%, 4) and persistently elevated blood pressure (14.7%, 5). The effective rate of thrombolytic therapy in the early termination group was significantly lower than that in the normal treatment group (P < 0.05). The rate of early neurological deterioration in the early termination group was significantly higher than that in the normal treatment group (P < 0.05). There was no significant difference in the incidence of symptomatic intracranial hemorrhage after thrombolysis between the two groups (P > 0.05). The average mRS score of the early termination group was significantly higher than that of the normal treatment group (P < 0.05). Multivariate analysis indicated that early termination of thrombolytic therapy and cumulative dosage of rt-PA before termination were the main factors affecting the 3-month prognosis. CONCLUSION: Subjective wishes of family members and persistently elevated blood pressure may be the main causes of early termination of thrombolysis, and the 3-month prognosis of patients could be adversely affected by early termination of thrombolytic therapy and cumulative dosage of rt-PA. Certain measures, such as popularizing thrombolytic health education and optimizing blood pressure management before and during thrombolysis, may be helpful for the normal operation of intravenous thrombolysis.

The way of Qu-making significantly affected the volatile flavor compounds in Huangjiu (Chinese rice wine) during different brewing stages.

The volatile flavor compounds of Huangjiu (Chinese rice wine) brewed from different raw materials were obviously different, but there were few studies on the volatile flavor compounds of Huangjiu brewed from different wheat Qu at different brewing stages. In this paper, headspace-solid phase microextraction combined with gas chromatography-mass spectrometry, combined with principal component analysis and sensory evaluation, was used to determine the volatile flavor compounds in Huangjiu brewed from wheat Qu made by hand and wheat Qu made by mechanical. The results showed that there were significant differences in the contents and types of volatile flavor substances in Huangjiu brewed from different wheat Qu at fermentation stages, and the prefermentation and postfermentation Huangjiu samples could be well distinguished from each other. Compared with the Huangjiu brewed from wheat Qu made by mechanical, the Huangjiu brewed from wheat Qu made by hand has stronger aroma and better taste.

Association between Cognitive Decline and Altered Cerebral Perfusion in Adults with Moyamoya Disease after Revascularization.

INTRODUCTION: Certain studies have observed that patients with moyamoya disease (MMD) have cognitive decline after revascularization. Thus, this study analyzed the relationship between cognitive decline and altered cerebral perfusion after revascularization. METHODS: Here, 313 adult patients with MMD underwent single unilateral revascularization. First, cognitive function was scored using a Mini-Mental Scale (MMSE) and Montreal cognitive function scale (MoCA) before and 3 months after the operation (superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis). Then, computed tomography perfusion was performed before and 1 week after the operation to assess the cerebral perfusion. RESULTS: Our data showed that cognitive function decreased in 55 cases (17.6%) after revascularization. Furthermore, the incidence of cerebral hyperperfusion (CHP) was significantly higher in the cognitive decline group (49/55) than in the cognitive nondecline group (89.1% vs. 5.4%, p < 0.001). Results also showed that although all 55 patients had postoperative cognitive decline, 47 experienced relative cerebral blood flow (CBF) decrease at a relatively distant area of the anastomosis compared with that before the operation, which was significantly higher than in patients without cognitive decline (85.5% vs. 1.94%, p < 0.001). In addition, 41 patients had a simultaneous occurrence of local CHP and paradoxical CBF decrease at a relatively distant anastomosis area, which indicated the incident of watershed shift (WS). As observed, WS occurred in 74.5% of patients with cognitive decline, significantly higher than in patients without cognitive decline (74.5% vs. 0%, p < 0.0001). Through multiple logistic regression analysis, WS was also observed to be a strong independent risk factor for predicting postoperative cognitive decline 3 months after revascularization (odds ratio 17.780, 95% confidence interval 1.668-18.564; p = 0.017). CONCLUSION: Therefore, cognitive decline in patients with MMD after revascularization is related to WS, leading to an uneven distribution of CBF.

Gut-Lung Axis: Microbial Crosstalk in Pediatric Respiratory Tract Infections.

The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children's intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.

The sensory and flavor characteristics of Shaoxing Huangjiu (Chinese rice wine) were significantly influenced by micro-oxygen and electric field.

In order to improve the high cost of equipment and difficult management caused by the natural aging of Chinese rice wine (Huangjiu), micro-oxygen (MO) and electric field (PEF) technology are used to accelerate the aging of Huangjiu. The results showed that micro-oxygen and electric field have a significant effect on the sensory characteristics and flavor characteristics of Huangjiu. Compared with the naturally aged Huangjiu, the flavor compounds of Huangjiu treated with micro-oxygen and electric field increase significantly. Based on principal component analysis, Huangjiu processed at 0.35 mg L/day or 0.5 mg L/day combined electric field exhibited similar flavor to the natural aged Huangjiu, which was highly associated with long-chain fatty acid ethyl esters (C13-C18). Moreover, partial least squares regression demonstrated that sensory attributes of cereal aroma and astringency were highlighted after aging time, while fruit aroma, continuation, and full body were dominant after micro-oxygen and electric field treatment. Micro-oxygen and electric field effectively enhanced the quality of Huangjiu, which could be applied in other alcoholic beverages.

Risk Factors for Hemorrhagic Transformation After Intravenous Thrombolysis in Acute Cerebral Infarction: A Retrospective Single-Center Study.

OBJECTIVE: To investigate the risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis using a recombinant tissue plasminogen activator (r-tPA) in acute cerebral infarction. METHODS: Patients with acute cerebral infarction receiving r-tPA thrombolysis in Shanghai Eastern Hospital were retrospectively studied. Based on the cranial computed tomography or magnetic resonance imaging examination, after the intravenous thrombolysis, the patients were divided into 2 groups: an HT group and a non-HT group. The information was collected before or after thrombolysis. RESULTS: A total of 162 patients were included in the analysis. The age ranged from 25 to 86 years, with an average age of 65.6 ± 10.6 years. The average time from disease onset to thrombolysis was 188 ± 53.1 minutes. Cranial computed tomography or magnetic resonance imaging showed that 20 patients (12.3%) had HT after thrombolysis. Using univariate analysis, history of atrial fibrillation, positive expression of urinary protein, and high National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis, we found that there was a significant difference between the HT and non-HT group (P < 0.05) in the level of mean systolic pressure (MSP) 24 hours after thrombolysis. Multivariate logistic regression analysis indicated that age ≥80 years, MSP ≥140 mm Hg, NIHSS score, and fibrinogen concentration before thrombolysis were risk factors for HT after thrombolysis in patients with acute cerebral infarction. CONCLUSIONS: Age, MSP, NIHSS score, and fibrinogen concentration before thrombolysis are risk factors for HT after thrombolysis in acute cerebral infarction. These 4 factors should be carefully taken into account before thrombolysis.

Y-shaped Folic Acid-Conjugated PEG-PCL Copolymeric Micelles for Delivery of Curcumin.

BACKGROUND: Curcumin is a natural hydrophobic product showing anticancer activity. Many studies show its potential use in the field of cancer treatment due to its safety and efficiency. However, its application is limited due to its low water-solubility and poor selective delivery to cancer. OBJECTIVE: A Y-shaped folic acid-modified poly (ethylene glycol)-b-poly (ε-caprolactone)2 copolymer was prepared to improve curcumin solubility and realize its selective delivery to cancer. METHOD AND RESULTS: The copolymer was synthesized through selective acylation reaction of folic acid with α- monoamino poly(ethylene glycol)-b-poly(ε-caprolactone)2. Curcumin was encapsulated into the copolymeric micelles with 93.71% of encapsulation efficiency and 11.94 % of loading capacity. The results from confocal microscopy and cellular uptake tests showed that folic acid-modified copolymeric micelles could improve cellular uptake of curcumin in Hela and HepG2 cells compared with folic acid-unmodified micelles. In vitro cytotoxicity assay showed that folic acid-modified micelles improved anticancer activity against Hela and HepG2 cells in comparison to folic acidunmodified micelles. Meanwhile, both drug-loaded micelles demonstrated higher activity against Hela cell lines than HepG2. CONCLUSION: The research results suggested that the folic acid-modified Y-shaped copolymeric micelles should be used to enhance hydrophobic anticancer drugs' solubility and their specific delivery to folic acid receptors-overexpressed cancer.

Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures.

Hypoxic and low-glucose stressors contribute to neuronal death in many brain diseases. Astrocytes are anatomically well-positioned to shield neurons from hypoxic injury. During hypoxia/ischemia, lactate released from astrocytes is taken up by neurons and stored for energy. This process is mediated by monocarboxylate transporters (MCTs) in the central nervous system. In the present study, we investigated the ability of astrocytes to protect neurons from oxygen- and glucose-deprivation (OGD) injury via an MCT-dependent mechanism in vitro. Primary cultures of neurons, astrocytes, and astrocytes-neurons derived from rat hippocampus were subjected to OGD, MCT inhibition with small interfering (si)RNA. Cell survival and expression of MCT4, MCT2, glial fibrillary acidic protein, and neuronal nuclear antigen were evaluated. OGD significantly increased cell death in neuronal cultures and up-regulated MCT4 expression in astrocyte cultures, but no increased cell death was observed in neuron-astrocyte co-cultures or astrocyte cultures. However, neuronal cell death in co-cultures was increased by exposure to MCT4- or MCT2-specific siRNA, and this effect was attenuated by the addition of lactate into the extracellular medium of neuronal cultures prior to OGD. These findings demonstrate that resistance to OGD injury in astrocyte-neuron co-cultures occurs via an MCT-dependent mechanism.

MCT4-mediated expression of EAAT1 is involved in the resistance to hypoxia injury in astrocyte-neuron co-cultures.

Hypoxic stressors contribute to neuronal death in many brain diseases. Astrocyte processes surround most neurons and are therefore anatomically well-positioned to shield them from hypoxic injury. Excitatory amino acid transporters (EAATs), represent the sole mechanism of active reuptake of glutamate into the astrocytes and neurons and are essential to dampen neuronal excitation following glutamate release at synapses. Glutamate clearance impairment from any factors is bound to result in an increase in hypoxic neuronal injury. The brain energy metabolism under hypoxic conditions depends on monocarboxylate transporters (MCTs) that are expressed by neurons and glia. Previous co-immunoprecipitation experiments revealed that MCT4 directly modulate EAAT1 in astrocytes. The reduction in both surface proteins may act synergistically to induce neuronal hyperexcitability and excitotoxicity. Therefore we hypothesized that astrocytes would respond to hypoxic conditions by enhancing their expression of MCT4 and EAAT1, which, in turn, would enable them to better support neurons to survive lethal hypoxia injury. An oxygen deprivation (OD) protocol was used in primary cultures of neurons, astrocytes, and astrocytes-neurons derived from rat hippocampus, with or without MCT4-targeted short hairpin RNA (shRNA) transfection. Cell survival, expression of MCT4, EAAT1, glial fibrillary acidic protein and neuronal nuclear antigen were evaluated. OD resulted in significant cell death in neuronal cultures and up-regulation of MCT4, EAAT1 expression respectively in primary cell cultures, but no injury in neuron-astrocyte co-cultures and astrocyte cultures. However, neuronal cell death in co-cultures was increased exposure to shRNA-MCT4 prior to OD. These findings demonstrate that the MCT4-mediated expression of EAAT1 is involved in the resistance to hypoxia injury in astrocyte-neuron co-cultures.

Influence of internal carotid artery stenosis, blood pressure, glycated hemoglobin, and hemoglobin level on fMRI signals of stroke patients.

OBJECTIVES: To identify the effect of internal carotid artery (ICA) stenosis, blood pressure (BP), glycated hemoglobin (HbA1c), and hemoglobin level on blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals in stroke patients. METHODS: A total of 18 stroke patients with acute cerebral infarction (13 males and 5 females) and 13 age-matched healthy controls (5 males and 8 females) were recruited. Among 18 stroke patients, 8 had significant ICA stenosis (> 50%) and 10 had nonsignificant ICA stenosis (< 50%). During handgrip task, stroke patients and normal controls were allowed to use their hands coincided with infarction and right hands, respectively. RESULTS: The mean BOLD signals in patients with significant ICA stenosis were significantly less than that in patients with nonsignificant ICA stenosis. Mean arterial pressure (MAP) was significantly correlated with activated voxels of Brodmann area 4 (P < 0.01) and total activated voxels (P  =  0.007), whereas hemoglobin and HbA1c showed no significant correlation with activated voxels of Brodmann area 4 or total activated voxels (P > 0.05). CONCLUSION: It is suggested that both ICA stenosis and arterial BP could influence BOLD signal, while HbA1c and hemoglobin level had no effect on BOLD signal.

Poly(ethylene glycol) amphiphilic copolymer for anticancer drugs delivery.

Poly(ethylene glycol) is a water-soluble polymer. Due to its high safety and biocompatibility, it has been widely used to prepare amphiphilic copolymers for drug delivery. These copolymers can enhance water-solubility of hydrophobic drugs, improve their pharmacokinetic parameters and control their release from corresponding nanocarriers formed by its self-assembly. Anticancer drugs have some shortcomings such as lower water-solubility, bad targeting and some serious side-effects, which limit their applications and are dangerous to patients. So encapsulation of anticancer drugs into nanocarriers originated from its copolymeric derivates can improve their absorption, distribution, metabolism and excretion with better release properties and activities against cancer cells, increase their therapeutic effects, and realize their passive or active target delivery through structure modification. Recent research development of its drug delivery systems for anticancer drugs will be discussed.

Y-shaped biotin-conjugated poly (ethylene glycol)-poly (epsilon-caprolactone) copolymer for the targeted delivery of curcumin.

In order to improve curcumin's low water-solubility and selective delivery to cancer, we reported ligand-mediated micelles based on a Y-shaped biotin-poly (ethylene glycol)-poly (epsilon-caprolactone)2 (biotin-PEG-PCL2) copolymer. Its structure was characterized by (1)H NMR. The blank and drug-loaded micelles obtained by way of thin-film hydration were characterized by dynamic light scattering, X-ray diffraction, infrared spectroscopy and hemolytic test. Curcumin was loaded into micelles with a high encapsulating efficiency (93.83%). Curcumin's water-solubility was enhanced 170,400 times higher than free curcumin. Biotin-PEG-PCL2 micelles showed slower drug release in vitro than H2N-PEG-PCL2 micelles. In vitro cellular uptake and cytotoxicity tests showed that higher dosage of curcumin might overcome the effect of slow release on cytotoxicities because of its higher uptake induced by biotin, resulting in higher anticancer activities against MDA-MB-436 cells. In brief, Y-shaped biotin-PEG-PCL2 is a promising delivery carrier for anticancer drug.

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone) copolymer micelles for the delivery of curcumin.

PURPOSE: To improve curcumin's pharmacokinetic, in vitro cytotoxicity and release property. METHODS: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and ε-caprolactone as raw materials. Its structure was characterized by (1)H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. RESULTS: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 × 10(5) times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model ([Formula: see text] = 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT0-∞, t1/2z and AUC0-∞ of Curcumin-loaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. CONCLUSIONS: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.

Linolenic acid-modified PEG-PCL micelles for curcumin delivery.

In this study, a novel linolenic acid-modified poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer was prepared through radical addition, ring-opening polymerization, and N-acylation reactions. Its structure was characterized by (1)H NMR and GPC. Micelles were developed by thin-film hydration and used as a delivery system for curcumin with high drug loading capacity of 12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was increased to 2.05 mg/mL, which was approximately 1.87×10(5) times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8±0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin existed in the polymeric matrices under π-π conjugation and hydrogen bond interaction with the copolymer. In vitro drug release studies indicated that the curcumin release from linolenic acid-modified copolymer micelles met controlled release, and its release rate was less than that from the linolenic acid-unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells demonstrated that the additional π-π conjugation could affect curcumin's anticancer activity through reducing its release from micelles. Hemolysis test and intravenous irritation test results revealed that the linolenic acid-modified copolymer was safe for intravenous injection. The plasma AUC0-∞ and MRT0-∞ of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher than that of control solution, respectively. The CLz was also decreased by 2.75-fold. So, this linolenic acid-modified copolymer might be a carrier candidate for curcumin delivery.

MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells.

Studies have shown that the expression of CD133, leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5), and ATP binding cassette (ABC)G2 proteins is associated with malignancy and poor prognosis in colon cancer. However, molecular regulation mechanism of the three proteins has not been elucidated. Here, we report that microRNA-142-3p (miR-142-3p) inhibits the expression of CD133, Lgr5, and ABCG2 in colon cancer cells by binding to both the 3'-untranslated region and the coding sequences of the three genes. The miR-142-3p was markedly decreased in colon cancer specimens, in which it was negatively correlated with the expression of CD133, Lgr5, and ABCG2. Reduction of miR-142-3p corresponds to poor differentiation and bigger tumor size in colon cancers. Moreover, miR-142-3p levels were reduced in cells that formed spheres compared to cells that were cultured in regular media. Transfection of miR-142-3p mimics in colon cancer cells downregulated cyclin D1 expression, induced G1 phase cell cycle arrest, and elevated the sensitivity of the cells to 5-fluorouracil. Furthermore, OCT4 suppressed miR-142-3p, and hypomethylation of the OCT4 promoter was associated with a reduction in miR-142-3p. Finally, the miR-142-3p inhibited the growth of colon cancer cells in vivo, which was accompanied by the downregulation of CD133, Lgr5, and ABCG2 in tumor tissues. Our results elucidate a novel regulation pathway in colon cancer cells and suggest a potential therapeutic approach for colon cancer therapy.

A novel PET marker for in vivo quantification of myelination.

C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type mouse brain, a pattern that was also consistently observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively labeled myelinated regions with high specificity. Biodistribution studies showed abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole brain at 5 min post injection and prolonged retention in the brain with 1.37% injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the radioactivity concentration to the level of myelination in the brain. These studies suggest that MeDAS is a sensitive myelin probe that provides a direct means to detect myelin changes in the brain. Thus, it can be used as a myelin-imaging marker to monitor myelin pathology in vivo.