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Oral leukoplakia is one of the most common oral potentially malignant disorders (OPMDs) and its malignant transformation to oral cancer is highly associated with chronic inflammation. Extracellular vesicles (EVs) or exosome-delivered microRNAs modulate inflammatory responses and alleviate irritations that predisposes to cancer. We previously reported that microRNA-185 (miR-185) was significantly decreased in the buccal tissue of patients with oral cancer. In this study, we utilized genetically modified mesenchymal stem cells (MSCs) derived EVs with high expression of miR-185 to pasted MSC-EV-miR-185 on buccal lesions in dimethylbenzanthracene (DMBA) induced OPMD model. We found that treatment with MSC-EV-miR-185 remarkably attenuated inflammation severity and significantly decreased the incidence and the number of dysplasia in the OPMD tissue. Immunohistochemistry showed significantly decreased expression of proliferation marker PCNA and angiogenic marker CD31 in the lesion treated with MSC-EV-miR-185. Furthermore, miR-185 specifically targeted Akt genes by promoting activation of the apoptotic pathway, confirmed by the increased levels of activated caspase-3 and 9. In conclusion, genetically modified MSC-derived EVs enriched with miR-185 alleviate inflammatory response, inhibit cell proliferation and angiogenesis, and induce cell apoptosis, suggesting that their potential role as a novel therapeutic option for OPMD. [ABSTRACT FROM AUTHOR]

Layer-by-layer (LBL) technique is a well-established method for the formation of nanocapsules, which could encapsulate nanoparticles by polyelectrolyte and has received great interest in some areas of research. In this study, colloidal gold nanoparticles (AuNPs) were used as a vehicle for loading horseradish peroxidase (HRP), and AuNPs-HRP was encapsulated by using LBL technique to form a signal amplification nanocapsule probe. Based on the probe, an immunoassay was developed for the detection of imidacloprid in agricultural food samples (rice, pear and cabbage). The IC50 value of the assay was 0.11 ng mL−1 which was 8-9954 times lower than those of traditional ELISAs and well below the maximum residue limits (MRLs) permitted by the European Union (EU). The recoveries of imidacloprid from three different samples were 80.34–120.84% that had a good correlation (R2 = 0.9739) with those obtained by the commercial kit. The developed assay could provide a sensitive method for detection of imidacloprid. [ABSTRACT FROM AUTHOR]

The existence of Bi-fluctuation dispersing in Na0.5Bi0.5TiO3 (NBT) relaxor ferroelectric is hinted in other recent studies. However, this fluctuation has not been directly observed yet. We introduce the Bi-rich nano-regions with different sizes in a series of NBT ceramics by the slight excess of Bi3+ content. The crystal symmetries of the Bi-rich nano-regions and the NBT matrix are rhombohedral. The lattice parameters of the nano-regions are larger than those of the matrix in NBT ceramics, which were confirmed by the X-ray diffraction Rietveld refinement, TEM techniques and first-principles calculation. Also, the disorder-induced nano-regions appearing as Bi-fluctuation are associated with the complex phase transitions and the high-frequency relaxor behaviour of NBT suggested by the dielectric measurements and Raman spectra. [ABSTRACT FROM AUTHOR]

Protein kinase CK2 is a ubiquitously expressed kinase in eukaryotes, which is known to phosphorylate many protein substrates. Because CK2 is involved in the regulation of various signaling pathways, we wondered whether CK2 participated in the regulation of ionizing radiation (IR) induced biological process. In this study, we investigated the effect of IR on the subcellular localization and kinase activity in human non-small cell lung cancer (NSCLC) cells. Immunofluorescent results showed that CK2 subunits shuttle into the nucleus mostly beginning 1 h after IR and lasting more than 6 h. We also conducted in vitro kinase assay and observed an increase in CK2 kinase activity at 6 h after IR. Furthermore, an increase in S phase was observed at 6 h after IR. Colony formation assay results demonstrated that CK2 inhibitor CX-4945 significantly enhanced the effect of irradiation in NSCLC cells. These results indicated that CK2 may be implicated in the regulation of IR-induced biological process. [ABSTRACT FROM AUTHOR]

Temperature-constrained topology optimization for thermo-mechanical coupled problems under a design-dependent temperature field considering the thermal expansion effect remains an open problem. A temperature-constrained topology optimization method is proposed for thermo-mechanical coupled problems. In this article, the temperature values at the heat sources are constrained. The numerical results reveal that the temperature constraints play an important role in topology optimization of thermo-mechanical coupled problems. The optimized structure obtained by the presented method not only has certain strength but also decreases the temperature significantly compared with structures obtained by other methods without considering temperature constraints. The proposed method is applied to the design of the cooling system of a battery package. Numerical examples verify the efficiency of the presented method. [ABSTRACT FROM AUTHOR]

Container technology can effectively control soil environment and nutrient status to obtain the optimal plant growth condition. Peat, green waste compost (GWC), soil and perlite were used as substrate materials to study the effects of different substrate ratios on growth and physiology of 1.5-year-old Sequoia sempervirens container seedlings. The optimal substrate ratio of S. sempervirens container seedlings was obtained by L9 (34) orthogonal design and was finally evaluated by principal component analysis. The volume ratio of peat: GWC: soil: perlite of 4: 1.5: 1: 2 was the best substrate ratio for S. sempervirens across all parameters, whose porosity, bulk density (BD) and gas-water ratio (GWR) were within the ideal ranges. The concentrations of total nitrogen (TN) of 1.40% and total phosphorus (TP) of 0.13% were the highest among the nine different substrates. The total potassium (TK) and electrical conductivity (EC) were 0.13% and 0.70 ms cm−1, respectively. In addition, the plant height and ground diameter growing in the substrate were increased by 28% and 39% compared to their respective initial values. The content of peat and GCW had significant effects on growth (p < 0.01). The GWR in T2 (peat: GWC: soil: perlite = 6: 1: 0.5: 2) and T6 (peat: GWC: soil: perlite = 4: 0.5: 0.5: 1) are not suitable for S. sempervirens container seedlings. The PCA ranking of the 9 groups of substrates is: T8 > T1 > T4 > T3 > T2 > T5 > T7 > T9 > T6. The combination of peat, GWC, soil and perlite in an appropriate ratio could provide a good environment for S. sempervirens container seedlings. [ABSTRACT FROM AUTHOR]

Bioresorbable vascular scaffolds are expected to replace the traditional metal stent, avoiding the long-term complications of metal stents. However, it is hard for the traditional scaffold manufacturing process to meet the requirements of individualized treatment for vascular lesions, which requires different morphologies. Here, we used a new method of scaffold manufacturing, three-dimensional printing technology, to prepare bioresorbable vascular scaffolds. The fabricated scaffold was loaded with sirolimus mixed with scaffold preparation material for slow drug release. The engineered, drug- loaded, bioresorbable vascular scaffold (BVS) was analyzed and tested in vivo. The scaffolds produced by three-dimensional printing technology exhibited good mechanical properties and in vitro degradation performance. The results also suggested that these scaffolds could maintain effective radial strength after long-term degradation and sustained release of the drug. As a new scaffold preparation method, it may provide a promising idea for developing bioresorbable vascular scaffold technology. [ABSTRACT FROM AUTHOR]

Taking an ecological perspective, we examine how two types of interdependence among business incubators located in the same region - mutualism and competition - affect the performance of these incubators. Using a dataset on Chinese National Technology Business Incubators (NTBIs) from 2008 to 2012, we show that incubator interdependence, measured by regional incubator density, has an inverted U-shaped relationship with a focal NTBI’s performance. We further explore how incubator ownership (government-owned vs. non-government-owned) and strategy (specialised vs. diversified) moderate the above relationship in China’s transitional economy. The results indicate that the linkage between incubator interdependence and incubation performance is stronger for non-government-owned and diversified business incubators. Theoretical and managerial implications are discussed. [ABSTRACT FROM AUTHOR]

Context: Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases. Objective: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo. Materials and methods: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry. Results: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p < 0.05) and notably alleviated synovial hyperplasia and cartilage degradation in joints. Different from methotrexate, MAN significantly augmented CD25+ cells distribution (from 2.72 to 3.35%) and IL-10 secretion (from 202.4 to 241.2 pg/mL) in CIA rat blood. Meanwhile, MAN induced a greater IL-17 decrease and a FOXP3 increase in immune organs than MTX. Reduced TLR4 and IL-17 expression and elevated FOXP3 expression in joints also occurred under MAN treatment. Conclusions: MAN protected joints from destruction in CIA rats and exerted synergistic effects with methotrexate by improving immune microenvironment. The combination regimen could bring additional benefits to rheumatoid arthritis patients. [ABSTRACT FROM AUTHOR]

Hemoglobin A1c (HbA1c) is a widely utilized biomarker for the diagnosis and management of diabetes mellitus. Here, we describe an α1-globin chain hemoglobin variant and investigate its effect on HbA1c measurement. A 26-year-old pregnant woman was suspected to harbor a hemoglobin variant following HbA1c measurement during a routine prenatal examination using D10 (Bio-Rad). An oral glucose tolerance test (OGTT) was performed using an AU5800 clinical chemistry system (Beckman Coulter). HbA1c was reanalyzed using VII-T 2.0 (Bio-Rad), Capillarys 2 Flex Piercing (C2FP, HbA1c program, Sebia), Premier Hb9210 (Trinity Biotech), and Cobas c501 (Cobas Tina-quant Hemoglobin A1c Gen.3). Glycated albumin (GA) level was also quantified using an enzymic method GA Kit (Lucica GA-L, Japan). Hemoglobin analysis was performed using high performance liquid chromatography on the Bio-Rad Variant II (β-thalassemia short program) and capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and β genes was also conducted. HbA1c was initially measured at 16.0% (151 mmol/mol) using the D10 (Bio-Rad). Her OGTT result was normal. Subsequently, HbA1c values determined by VII-T 2.0, C2FP, Premier Hb9210, and Cobas c501 were 4.8% (29 mmol/mol), 4.9% (30 mmol/mol), 4.6% (27 mmol/mol), and 4.8% (29 mmol/mol), respectively. The glycated albumin level was 12.3% (reference: 10.8 ∼ 17.1%). Hemoglobin analyzed using CE and HPLC revealed an abnormal hemoglobin. By Sanger sequencing, we identified a transition mutation in the α1 gene Hb Shantou [α127(H10)Lys > Glu; HBA1: c.382 A > G]. Clinically silent variants may interfere with HbA1c determination by common methods. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the third most common cancer in the female reproductive organs and epithelial ovarian cancer has the highest lethality of all gynecological cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of several types of cancer other than ovarian cancer. In this study, we exposed the ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and luteolin). MTT and wound healing assays demonstrated that all three treatments suppressed the proliferation and migration of the ovarian cancer cells. In addition, western blotting and ELISA assays showed that the expression levels of MMP2 and MMP9 gradually decreased after treatment with increasing concentrations of ellagic acid and luteolin. To confirm our findings in thein vitroexperiments, we used another ovarian cancer cell line, ES-2, in nude mice experiments. All three treatments inhibited tumor growth without obvious side-effects. Furthermore, compared with the control group, the expression levels of MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a promising candidate for further preclinical testing for treatment of human ovarian cancer. [ABSTRACT FROM PUBLISHER]

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performedin vitroassays with human nasopharyngeal carcinoma CNE-2 cells andin vivoassays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation. [ABSTRACT FROM PUBLISHER]

In this paper, a gammadion stereo-structure (GSS) chiral metamaterial (CMM) is described and numerically analysed at optical frequencies. The influence of the geometry of the proposed CMM on the optical properties was studied systematically. The numerical simulations exhibit that the giant circular dichroism (CD) effect, optical activity and negative refraction can be obtained by properly selecting the geometric parameters, respectively. Given the pronounced optical effects and the negative refraction property of stereo-structure CMM, many applications in ultra-compact polarization components, integrated photonics, plasmonic-enhanced sensing of biochemical substances and CD spectroscopic analysis can be envisioned easily. [ABSTRACT FROM PUBLISHER]

Polycyclic aromatic hydrocarbons (PAHs) have mutagenic and carcinogenic properties. Acenaphthene and pyrene were members of 16 PAHs which were listed as the priority pollutants in water environment by US Environmental Protection Agency. The reported instrumental methods and immunoassays did not meet the need for simple and sensitive detection of acenaphthene and pyrene. In this study, a monoclonal antiobody having high affinities with acenaphthene and pyrene was produced and an indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed for sensitive detection of acenaphthene and pyrene in water sample. The linear range of the assay was between 3.53 and 41.98 ng mL−1. The sensitivity was 12.17 ng mL−1which was more sensitive than those of reported ELISAs. The average recovery of acenaphthene and pyrene from three kinds of water samples was 99.08% and 98.45, respectively. The developed ELISA could be used for sensitive detection of acenaphthene and pyrene in water samples. [ABSTRACT FROM PUBLISHER]

Celiac trunk aneurysms (CTAs) are rare and usually asymptomatic. Although most of these aneurysms can be treated with percutaneous embolization, some uncommon locations of the aneurysm may make this approach impossible. We report a patient with a celiac trunk aneurysm (CTA) and a proximal splenic artery aneurysm (SAA). Due to the size and location of these two aneurysms, after multidisciplinary discussion, endovascular management was considered inappropriate and they were treated by laparoscopic ligation of the two aneurysms and revascularization. This procedure offers good postoperative recovery with good preservation of the visceral function. Some collateral vessels in the viscera were obvious on postoperative day 7. [ABSTRACT FROM PUBLISHER]

We report a novel α2-globin chain hemoglobin (Hb) variant in a 23-year-old female of Chinese Han nationality. The Hb variant can be detected by glycated Hb electrophoresis (CapillaryS2, Hb A1c program). However, Hb fractions analyzed by capillary electrophoresis (CE) (CapillaryS2, Hb program) and high performance liquid chromatography (HPLC), (VARIANT II™ β-Thalassemia Short Program) showed no suspicious Hb variant. Sanger sequencing revealed a novel mutation [α67(E16)Thr→Ile, HBA2: c.203C>T]. We named this novel variant Hb Sichuan after the geographic origin of the proband. [ABSTRACT FROM AUTHOR]

We report a novel variant found in a female from Guilin municipality in the Guangxi Zhuang Autonomous Region of the People's Republic of China. This variant can be readily detected by both cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing revealed a novel mutation on the β-globin gene [β65(E9)Lys→Glu (AAG>GAG); HBB: c.196A>G]. We named this novel hemoglobin (Hb) variant Hb Guangxi for the place of origin of the proband. [ABSTRACT FROM AUTHOR]

Searching for the contact points between wheels and rails is important because these points represent the points of exerted contact forces. In order to obtain an accurate contact point and an in-depth description of the wheel/rail contact behaviours on a curved track or in a turnout, a method with improved accuracy in three dimensions is proposed to determine the contact points and the contact patches between the wheel and the rail when considering the effect of the yaw angle and the roll angle on the motion of the wheel set. The proposed method, with no need of the curve fitting of the wheel and rail profiles, can accurately, directly, and comprehensively determine the contact interface distances between the wheel and the rail. The range iteration algorithm is used to improve the computation efficiency and reduce the calculation required. The present computation method is applied for the analysis of the contact of rails of CHINA (CHN) 75 kg/m and wheel sets of wearing type tread of China's freight cars. In addition, it can be proved that the results of the proposed method are consistent with that of Kalker's program CONTACT, and the maximum deviation from the wheel/rail contact patch area of this two methods is approximately 5%. The proposed method, can also be used to investigate static wheel/rail contact. Some wheel/rail contact points and contact patch distributions are discussed and assessed, wheel and rail non-worn and worn profiles included. [ABSTRACT FROM AUTHOR]

We report a novel β-globin chain variant, Hb Shenzhen [β90(F6)Glu→Ala, HBB: c.272A>C], in a 52-year-old Chinese individual. The hemoglobin (Hb) variant takes the position of the Hb D zone using capillary electrophoresis. Sanger sequencing revealed a novel base mutation on the β-globin gene, HBB: c.272A>C, that resulted in a transition of glutamic acid to alanine at exon 2 of the β-globin gene. We named this novel variant Hb Shenzhen for the geographic origin of this proband. [ABSTRACT FROM AUTHOR]

We report here a novel α1-globin chain variant, Hb Hubei [α114(GH2)Pro→His, HBA1: c.344C>A], in a Chinese individual. The proband, a 28-year-old Chinese female, was discovered following routine Hb A1c analysis using cation exchange high performance liquid chromatography (HPLC). Sanger sequencing revealed a novel missense mutation, HBA1: c.344C>A (CCC>CAC), in exon 2 of the α1-globin gene. The mutation caused a transition of proline to histidine at position α114(GH2) on the α1-globin chain. This new variant was named Hb Hubei after the geographic origin of the proband. [ABSTRACT FROM AUTHOR]

Background: Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, such as pancreatic, colon and gastric cancers. Previous studies have shown that the specific receptor-binding property of CCK for CCK receptors (CCKRs) can be exploited to produce immunotoxins (ITs) that target cancer cells overexpressing CCK receptors. Purpose: Construct a new IT-targeting CCKR-overexpressing colon cancers. Methods: To construct the CCKR-targeted IT, a reverse CCK8 peptide was fused with a modified 38-kDa truncated form of the Pseudomonas exotoxin (PE38KDEL). An efficient immunoaffinity purification procedure was used to produce a PE38-based IT. Several analyses, including CCK8 competition and indirect immunofluorescence assays, were performed to confirm the interaction between rCCK8 and CCKR. After cytotoxic assays on several cell lines, the anti-tumor activity of the new IT was detected in nude mice. Results: The rCCK8PE38 IT showed specific cytotoxicity for two colon cancer cell lines and one gastric cancer cell line. After purification, 18-26 mg of pure rCCK8PE38 per 1 L of culture was obtained. Purified rCCK8PE38 showed high cytotoxicity in colon cancer cell lines with IC50 values of 0.8-3.5 ng/mL. The results of the CCK8 competition and indirect immunofluorescence assays showed that rCCK8 had a specific interaction with CCKR. Nude mice inoculated with HCT-8 tumor xenografts were treated with rCCK8PE38, which efficiently decreased the tumor size in those mice. Conclusions and discussion: All of these data suggest that rCCK8PE38 has potential as a new immunotherapy agent. Furthermore, the results of this study further support the high value of the immunoaffinity method for IT purification procedures. [ABSTRACT FROM AUTHOR]

A 61-year-old man with newly diagnosed INT-1 risk myelodysplastic syndrome - refractory cytopenia with multilineage dysplasia (MDS-RCMD) was not responsive to treatment, such as androgen, thalidomide, granulocyte - colony stimulating factor (G-CSF) combined with erythropoietin (EPO), interleukin-11 (IL-11) and thrombopoietin (TPO), and became transfusion dependent. Due to repeated blood transfusions, he developed platelet transfusion refractoriness (PTR) to platelets from cross-matched donors as well as random donors. Anti-HLA class I antibodies were positive with enzyme-linked immunosorbent assay; however, HLA-compatible platelet products were unavailable. PTR was unresponsive to high-dose immunoglobulin and plasma exchange. The patient was then treated with rituximab 375 mg/m2 on days 1 and 8, and 100 mg total dose on days 15 and 22. Already after the first dose of rituximab, the patient was able to received successful platelet transfusion from all donors. Therefore rituximab may be considered as a potential therapy for PTR. [ABSTRACT FROM AUTHOR]