Infrared spectra and electronic structural changes of DNTF under high pressure: experimental and theoretical studies.

3,4-Bis(3-nitrofurazan-4-yl)furoxan (DNTF) is a novel energetic material with an excellent performance and has attracted considerable attention. Motivated by recent theories and experiments, we had carried out experimental and theoretical studies on the high-pressure responses of vibrational characteristics, in conjunction with structural and electronic characteristics. It is found that all observed infrared spectra peaks seem to shift towards higher frequencies. And the peaks attributed to N-Oc (coordinated oxygen atom) stretching vibrations become broader due to the decrease of lattice constants and the free region of DNTF crystals with the increase of pressure, where the a-direction is more sensitive to pressure. In addition, the non-covalent interaction between adjacent DNTF molecules in the same layer changes from the van der Waals interaction to the steric effect with the increase of pressure, and that between layers also changes from the van der Waals interaction to the π-π stacking interaction. More importantly, these results highlight that the increase of pressure may lead to the stability decrease and impact the sensitivity increase of DNTF. This study can deepen the understanding of the energetic material DNTF under high pressure and is of great significance for blasting and detonation applications of DNTF.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

α-Subunit Tyrosine Phosphorylation Is Required for Activation of the Large Conductance Ca2+-Activated Potassium Channel in the Rabbit Sphincter of Oddi.

Large conductance Ca2+-activated potassium (BKCa) channels are regulated by intracellular free Ca2+ concentrations ([Ca2+]i) and channel protein phosphorylation. In hypercholesterolemia (HC), motility impairment of the sphincter of Oddi (SO) is associated with abnormal [Ca2+]i accumulation in smooth muscle cells of the rabbit SO (RSOSMCs), which is closely related to BKCa channel activity. However, the underlying mechanisms regulating channel activity remain unclear. In this study, an HC rabbit model was generated and used to investigate BKCa channel activity of RSOSMCs via SO muscle tone measurement in vitro and manometry in vivo, electrophysiological recording, intracellular calcium measurement, and Western blot analyses. BKCa channel activity was decreased, which correlated with [Ca2+]i overload and reduced tyrosine phosphorylation of the BKCa α-subunit in the HC group. The abnormal [Ca2+]i accumulation and decreased BKCa channel activity were partially restored by Na3VO4 pretreatment but worsened by genistein in RSOSMCs in the HC group. This study suggests that α-subunit tyrosine phosphorylation is required for [Ca2+]i to activate BKCa channels, and there is a negative feedback between the BKCa channel and the L-type voltage-dependent Ca2+ channel that regulates [Ca2+]i. This study provides direct evidence that tyrosine phosphorylation of BKCa α-subunits is required for [Ca2+]i to activate BKCa channels in RSOSMCs, which may be the underlying physiological and pathologic mechanism regulating the activity of BKCa channels in SO cells.

Differentiation of Pseudoprogression from True Progressionin Glioblastoma Patients after Standard Treatment: A Machine Learning Strategy Combinedwith Radiomics Features from T1-weighted Contrast-enhanced Imaging.

BACKGROUND: Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T1-weighted contrast enhanced imaging(T1CE) in differentiating pseudoprogression from true progression after standard treatment for GBM. METHODS: Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T1CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T1CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity. RESULTS: No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists' assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively. CONCLUSION: T1CE-based radiomics showed better classification performance compared with radiologists' assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.

Assessment of Resistance to Cereal Cyst Nematode, Stripe Rust, and Powdery Mildew in Wheat-Thinopyrum intermedium Derivatives and Their Chromosome Composition.

Wide hybridization between wheat and wild relatives such as Thinopyrum intermedium is important for broadening genetic diversity and improving disease resistance in wheat. We developed 30 wheat-Th. intermedium derivatives. Here, we report assessments of their resistance to different pathogens including cereal cyst nematode (CCN; Heterodera spp.), Puccinia striiformis f. tritici Erikss. causing stripe rust, and Blumeria graminis f. tritici (DC.) Speer inciting powdery mildew. Under natural field infection, all the wheat-Th. intermedium lines were resistant to at least one of the pathogens, and four lines were resistant to multiple pathogens. Twenty-nine of 30 tested lines exhibited resistance to H. avenae, a dominant CCN species in wheat fields. Twenty-four lines were resistant to H. filipjevi, an emerging threat to wheat production. Tests of phenotypic responses in the naturally infected field nurseries identified six stripe rust-resistant lines and 13 powdery mildew-resistant lines. Mitotic observation demonstrated that these newly developed wheat-Th. intermedium derivatives included not only octoploid but also chromosome addition, substitution, and translocation lines. Chromosome compositions of the four lines resistant to multiple pathogens were analyzed by genomic in situ hybridization and fluorescence in situ hybridization. The octoploid lines Zhong 10-68 and Zhong 10-117 carried both intact Th. intermedium chromosomes and translocated chromosomes. Line Zhong 10-149 had 42 wheat chromosomes and two wheat ditelosomes plus a pair of T3BS·J translocated chromosomes. Line Zhong 10-160 carried 41 wheat chromosomes plus one pair of the J genome chromosomes of Th. intermedium. The multiple disease-resistant wheat-Th. intermedium derivatives, especially lines with chromosome counts close to that of common wheat, provide valuable materials for wheat resistance breeding programs.

PVT1 induces NSCLC cell migration and invasion by regulating IL-6 via sponging miR-760.

Non-small-cell lung carcinoma (NSCLC) accounts for approximately 80% of lung cancers with a high metastatic potential. Elucidating the mechanism of NSCLC metastasis will provide new promising targets for NSCLC therapy and benefit its prognosis. Plasmacytoma variant translocation 1 (PVT1) has been proven to be overexpressed in NSCLC. Although the oncogenic role of PVT1 in NSCLC has been reported, its mechanism remains unclear. Here, we verified that the knockdown of PVT1 inhibited NSCLC cell migration and invasion, and that its inhibitory role on A549 cells and H1299 cells was antagonized by interleukin-6 (IL-6) treatment. The results revealed that PVT1 regulates IL-6 by sponging miR-760 and identified the binding site of miR-760 in the 3'-UTR of IL-6. In conclusion, a new mechanism was revealed, wherein PVT1 regulates NSCLC cell migration and invasion via miR-760/IL-6, suggesting PVT1/miR-760/IL-6 as promising prognostic biomarkers and therapeutic targets for NSCLC metastasis.

Genome-Wide Association Mapping of Adult-Plant Resistance to Stripe Rust in Common Wheat (Triticum aestivum).

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a globally devastating disease of common wheat (Triticum aestivum L.), resulting in substantial economic losses. To identify effective resistance genes, a genome-wide association study was conducted on 120 common wheat lines from different wheat-growing regions of China using the wheat 90K iSelect SNP array. Seventeen loci were identified, explaining 9.5 to 21.8% of the phenotypic variation. Most of these genes were detected in the A (seven) and B (seven) genomes, with only three in the D genome. Among them, 11 loci were colocated with known resistance genes or quantitative trait loci reported previously, whereas the other six are likely new resistance loci. Annotation of flanking sequences of significantly associated SNPs indicated the presence of three important candidate genes, including E3 ubiquitin-protein ligase, F-box repeat protein, and disease resistance RPP13-like protein. This study increased our knowledge in understanding the genetic architecture for stripe rust resistance and identified wheat varieties with multiple resistance alleles, which are useful for improvement of stripe rust resistance in breeding.

Optimizing Texture Retrieving Model for Multimodal MR Image-Based Support Vector Machine for Classifying Glioma.

BACKGROUND: Accurate glioma grading plays an important role in patient treatment. PURPOSE: To investigate the influence of varied texture retrieving models on the efficacy of grading glioma with support vector machine (SVM). STUDY TYPE: Retrospective. POPULATION: In all, 117 glioma patients including 25, 29, and 63 grade II, III, and IV gliomas, respectively, based on WHO 2007. FIELD STRENGTH/SEQUENCE: 3.0T MRI/ T1 WI, T2 fluid-attenuated inversion recovery, contrast enhanced T1 , arterial spinal labeling, diffusion-weighted imaging (0, 30, 50, 100, 200, 300, 500, 800, 1000, 1500, 2000, 3000, and 3500 sec/mm2 ), and dynamic contrast-enhanced. ASSESSMENT: Texture attributes from 30 parametric maps were retrieved using four models, including Global, gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and gray-level size-zone matrix (GLSZM). Attributes derived from varied models were input into radial basis function SVM (RBF-SVM) combined with attribute selection using SVM-recursive feature elimination (SVM-RFE). The SVM model was trained and established with 80% randomly selected data of each category using 10-fold crossvalidation. The model performance was further tested using the remaining 20% data. STATISTICAL TESTS: Ten-fold crossvalidation was used to validate the model performance. RESULTS: Based on 30 parametric maps, 90, 240, 390, or 390 texture attributes were retrieved using the Global, GLCM, GLRLM, or GLSZM model, respectively. SVM-RFE was able to reduce attribute redundancy as well as improve RBF-SVM performance. Training data were oversampled by applying the Synthetic Minority Oversampling Technique (SMOTE) method to overcome the data imbalance problem; test results were able to further demonstrate the classifying performance of the final models. GLSZM using gray-level 64 was the optimal model to retrieve powerful image texture attributes to produce enough classifying power with an accuracy / area under the curve of 0.760/0.867 for the training and 0.875/0.971 for the independent test. Fifteen attributes were selected with SVM-RFE to provide comparable classifying efficacy. DATA CONCLUSION: When using image textures-based SVM classification of gliomas, the GLSZM model in combination with gray-level 64 and attribute selection may be an optimized solution. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1263-1274.

Preparation of Y2O3 Coated CaO Ceramic Cores with Anti-Hydration Performance and High-Interface Stability Against Interface Reaction of Ti-6Al-4V Alloys.

In this study, we describe a novel method for preparing Y2O3@CaO ceramic cores with anti-hydration performance and high-interface stability against interface reaction of Ti-6Al-4V alloys. The effect of Y2O3 coating on microstructure, mechanical, anti-hydration properties of ceramic cores and interface reaction with Ti-6Al-4V alloys was studied. The results show that the surface charge of Y2O3 and CaO are opposite at the pH value of 13, which might result in an electrostatic force and become the main driving force of Y2O3 particles absorb on the surface of CaO particles. The Y2O3 coating improved the anti-hydration properties of the CaO-based ceramic cores after sintering at 1450 °C. Meanwhile, the flexural strength improved from 11.2 to 18.8 MPa. At last, the interaction between the ceramic cores and Ti-6Al-4V metal were studied by centrifugal investment casting. Y2O3 coating can effectively reduce the interface reaction and the thickness of the interaction layer in the casting was less than 10 µm. The results suggest that the Y2O3@CaO ceramic with anti-hydration performance provide excellent mechanical and high-interface stability against interface reaction of Ti-6Al-4V alloys.

[A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease].

OBJECTIVE: To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). METHODS: The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34+ cells, and CD3+ cells were 14.6×108/kg, 5.86×106/kg, and 2.13×108/kg respectively. RESULTS: The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. CONCLUSIONS: Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.

Structural and advanced imaging in predicting MGMT promoter methylation of primary glioblastoma: a region of interest based analysis.

BACKGROUND: The methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients. METHODS: Ninety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher's exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables. RESULTS: MGMT promoter methylation was associated with tumor location and necrosis (P <  0.05). Significantly increased ADC value (P <  0.001) and decreased rCBF (P <  0.001) were associated with MGMT promoter methylation in primary glioblastoma. The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860; sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%; specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC and rCBF resulted in the highest AUC of 0.914. CONCLUSION: ADC and rCBF are promising imaging biomarkers in clinical routine to predict the MGMT promoter methylation in primary glioblastoma patients.

Radiomics strategy for glioma grading using texture features from multiparametric MRI.

BACKGROUND: Accurate glioma grading plays an important role in the clinical management of patients and is also the basis of molecular stratification nowadays. PURPOSE/HYPOTHESIS: To verify the superiority of radiomics features extracted from multiparametric MRI to glioma grading and evaluate the grading potential of different MRI sequences or parametric maps. STUDY TYPE: Retrospective; radiomics. POPULATION: A total of 153 patients including 42, 33, and 78 patients with Grades II, III, and IV gliomas, respectively. FIELD STRENGTH/SEQUENCE: 3.0T MRI/T1 -weighted images before and after contrast-enhanced, T2 -weighted, multi-b-value diffusion-weighted and 3D arterial spin labeling images. ASSESSMENT: After multiparametric MRI preprocessing, high-throughput features were derived from patients' volumes of interests (VOIs). The support vector machine-based recursive feature elimination was adopted to find the optimal features for low-grade glioma (LGG) vs. high-grade glioma (HGG), and Grade III vs. IV glioma classification tasks. Then support vector machine (SVM) classifiers were established using the optimal features. The accuracy and area under the curve (AUC) was used to assess the grading efficiency. STATISTICAL TESTS: Student's t-test or a chi-square test were applied on different clinical characteristics to confirm whether intergroup significant differences exist. RESULTS: Patients' ages between LGG and HGG groups were significantly different (P < 0.01). For each patient, 420 texture and 90 histogram parameters were derived from 10 VOIs of multiparametric MRI. SVM models were established using 30 and 28 optimal features for classifying LGGs from HGGs and grades III from IV, respectively. The accuracies/AUCs were 96.8%/0.987 for classifying LGGs from HGGs, and 98.1%/0.992 for classifying grades III from IV, which were more promising than using histogram parameters or using the single sequence MRI. DATA CONCLUSION: Texture features were more effective for noninvasively grading gliomas than histogram parameters. The combined application of multiparametric MRI provided a higher grading efficiency. The proposed radiomic strategy could facilitate clinical decision-making for patients with varied glioma grades. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1518-1528.

Structural and functional brain changes in perimenopausal women who are susceptible to migraine: a study protocol of multi-modal MRI trial.

BACKGROUND: As a common clinical symptom that often bothers midlife females, migraine is closely associated with perimenopause. Previous studies suggest that one of the most prominent triggers is the sudden decline of estrogen during perimenopausal period. Hormone replacement therapy (HRT) is widely used to prevent this suffering in perimenopausal women, but effective diagnostic system is lacked for quantifying the severity of the diseaase. To avoid the abuse and overuse of HRT, we propose to conduct a diagnostic trial using multimodal MRI techniques to quantify the severity of these perimenopausal migraineurs who are susceptible to the decline of estrogen. METHODS: Perimenopausal women suffering from migraine will be recruited from the pain clinic of our hospital. Perimenopausal women not suffering from any kind of headache will be recruited from the local community. Clinical assessment and multi-modal MR imaging examination will be conducted. A follow up will be conducted once half year within 3 years. Pain behavior, neuropsychology scores, fMRI analysis combined with suitable statistical software will be used to reveal the potential association between these above traits and the susceptibility of migraine. DISCUSSION: Multi-modal imaging features of both healthy controls and perimenopausal women who are susceptible to estrogen decline will be acquired. Imaging features will include volumetric characteristics, white matter integrity, functional characteristics, topological properties, and perfusion properties. Clinical information, such as basic information, blood estrogen level, information of migraine, and a bunch of neurological scale will also be used for statistic assessment. This clinical trial would help to build an effective screen system for quantifying the severity of illness of those susceptible women during the perimenopausal period. TRIAL REGISTRATION: This study has already been registered at Clinical Trials. gov (ID: NCT02820974 ). Registration date: September 28th, 2014.

Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

BACKGROUND: The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. METHODS: Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. RESULTS: Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. CONCLUSION: In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

Combination of IVIM-DWI and 3D-ASL for differentiating true progression from pseudoprogression of Glioblastoma multiforme after concurrent chemoradiotherapy: study protocol of a prospective diagnostic trial.

BACKGROUND: Standard therapy for Glioblastoma multiforme (GBM) involves maximal safe tumor resection followed with radiotherapy and concurrent adjuvant temozolomide. About 20 to 30% patients undergoing their first post-radiation MRI show increased contrast enhancement which eventually recovers without any new treatment. This phenomenon is referred to as pseudoprogression. Differentiating tumor progression from pseudoprogression is critical for determining tumor treatment, yet this capacity remains a challenge for conventional magnetic resonance imaging (MRI). Thus, a prospective diagnostic trial has been established that utilizes multimodal MRI techniques to detect tumor progression at its early stage. The purpose of this trial is to explore the potential role of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling imaging (3D-ASL) in differentiating true progression from pseudoprogression of GBM. In addition, the diagnostic performance of quantitative parameters obtained from IVIM-DWI and 3D-ASL, including apparent diffusion coefficient (ADC), slow diffusion coefficient (D), fast diffusion coefficient (D*), perfusion fraction (f), and cerebral blood flow (CBF), will be evaluated. METHODS: Patients that recently received a histopathological diagnosis of GBM at our hospital are eligible for enrollment. The patients selected will receive standard concurrent chemoradiotherapy and adjuvant temozolomide after surgery, and then will undergo conventional MRI, IVIM-DWI, 3D-ASL, and contrast-enhanced MRI. The quantitative parameters, ADC, D, D*, f, and CBF, will be estimated for newly developed enhanced lesions. Further comparisons will be made with unpaired t-tests to evaluate parameter performance in differentiating true progression from pseudoprogression, while receiver-operating characteristic (ROC) analyses will determine the optimal thresholds, as well as sensitivity and specificity. Finally, relationships between these parameters will be assessed with Pearson's correlation and partial correlation analyses. DISCUSSION: The results of this study may demonstrate the potential value of using multimodal MRI techniques to differentiate true progression from pseudoprogression in its early stages to help decision making in early intervention and improve the prognosis of GBM. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov ( NCT02622620 ) on November 18, 2015 and published on March 28, 2016.

Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

Multimodal MRI for early diabetic mild cognitive impairment: study protocol of a prospective diagnostic trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a risk factor for dementia. Mild cognitive impairment (MCI), an intermediary state between normal cognition and dementia, often occurs during the prodromal diabetic stage, making early diagnosis and intervention of MCI very important. Latest neuroimaging techniques revealed some underlying microstructure alterations for diabetic MCI, from certain aspects. But there still lacks an integrated multimodal MRI system to detect early neuroimaging changes in diabetic MCI patients. Thus, we intended to conduct a diagnostic trial using multimodal MRI techniques to detect early diabetic MCI that is determined by the Montreal Cognitive Assessment (MoCA). METHODS: In this study, healthy controls, prodromal diabetes and diabetes subjects (53 subjects/group) aged 40-60 years will be recruited from the physical examination center of Tangdu Hospital. The neuroimaging and psychometric measurements will be repeated at a 0.5 year-interval for 2.5 years' follow-up. The primary outcome measures are 1) Microstructural and functional alterations revealed with multimodal MRI scans including structure magnetic resonance imaging (sMRI), resting state functional magnetic resonance imaging (rs-fMRI), diffusion kurtosis imaging (DKI), and three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL); 2) Cognition evaluation with MoCA. The second outcome measures are obesity, metabolic characteristics, lifestyle and quality of life. DISCUSSION: The study will provide evidence for the potential use of multimodal MRI techniques with psychometric evaluation in diagnosing MCI at prodromal diabetic stage so as to help decision making in early intervention and improve the prognosis of T2DM. TRIAL REGISTRATION: This study has been registered to ClinicalTrials.gov ( NCT02420470 ) on April 2, 2015 and published on July 29, 2015.

Substituent electronic effects govern direct intramolecular C-N cyclization of N-(Biphenyl)pyridin-2-amines induced by hypervalent iodine(III) reagents.

The hypervalent iodine(III) reagent-induced the direct intramolecular C-N cyclization of N-(biphenyl)pyridin-2-amines to 6-arylbenzimidazoles and N-pyridinyl-9H-carbazoles is presented. The substituent electronic effects governing the formation of benzimidazoles and carbazoles from the reaction of N-(biphenyl)pyridin-2-amines with hypervalent iodine(III) reagents is investigated. Radical trapping and UV-vis spectroscopic experiments on the detection of the cation radical are carried out. Rational mechanisms for these reactions are presented. The selective intramolecular C-N and C-O cyclization of N-(biphenyl)acetamides based on the substituent electronic effects is also presented.

[Role of vascular cell adhesion molecule-1 in the mouse model of hepatic ischemia/reperfusion and the hematogenic metastasis].

OBJECTIVE: To investigate the effect of ischemia/reperfusion (I/R) on tumor metastasis in a experimental mouse model of hematogenous metastasis after I/R and to quantify expression of vascular cell adhesion molecule-1 (VCAM-1) during I/R. METHODS: An experimental mouse model of metastasis after partial hepatic I/R was designed to determine the effects of I/R on tumor metastasis to liver. Tumor loads were valued 14 days after operation. In addition, the expressions of alanine transaminase (ALT), aspartate transaminase (AST), and VCAM-1 were detected. RESULTS: Two hours after hepatic reperfusion, ALT and AST levels in ischemia 45-minute group and ischemia 30-minute group were significantly higher than in the sham group (all P < 0.05). Also, the changes of ALT and AST were more obvious in the ischemia 45-minute group than in ischemia 30-minute group (all P < 0.05). In the sham group, both ALT and AST slightly and transiently increased. ALT and AST in the ischemia 45-minute group and ischemia 30-minute group at 8 hours were both significantly higher than those at 2 hours reperfusion (P<0.05). The tumor load (valued by hepatic replacement area) and the expression of VCAM-1 in ischemic lobe were significantly larger in the ischemia 45-minute group than in the ischemia 30-minute group and sham group (P = 0.013, P = 0.007). However, there was no statistical difference on tumor load between the right lobe of sham operated mice and the right lobe (nonischemic lobes) of mice subjected to I/R (P = 0.089). Mouse survivals were significantly longer in the sham group than in the ischemia 30-minute group (P = 0.041) but were not significantly different between the ischemia 45-minute group and ischemia 30-minute group (P = 0.055). VCAM-1 expression in ischemia 45-minute group was significantly higher than in ischemia 30-minute group and sham group(P = 0.003, P < 0.001), and it was positively correlated with the hepatic replacement area (r = 0.491, P = 0.045). CONCLUSION: Hepatic I/R promotes liver hematogenic metastasis of hepatocellular carcinoma in mice and at least in part, through the induction of VCAM-1 expression.

[Clinical effect of umbilical cord blood transplantation in 37 pediatric patients with hematologic malignancies: a single-center experience].

OBJECTIVE: To evaluate the clinical effect of umbilical cord blood transplantation (UCBT) in children with hematologic malignancies. METHODS: A retrospective analysis was performed on the clinical data of 37 pediatric patients with hematologic malignancies that consisted of 14 cases of acute lymphocyte leukemia, 9 cases of acute myeloid leukemia, 5 cases of juvenile myelomonocytic leukemia, 3 cases of chronic myeloid leukemia, 2 cases of acute mixed leukemia, 3 cases of myelodysplastic syndrome, and 1 case of lymphosarcomatous leukemia. Thirty-seven children with hematologic malignancies received UCBT from unrelated donors (34 cases) and related donors (3 cases). Grafts were 6/6 HLA-matched in 5 cases, 5/6 HLA-matched in 12 cases, 4/6 HLA-matched in 11 cases, and 3/6 HLA-matched in 9 cases. Before transplantation, these patients received rabbit antithymocyte globulin-containing conditioning regimen. The myeloablative conditioning regimen was given in 36 cases and the reduced-intensity conditioning regimen in one case. The median age of transplantation was 5.7 years, and the median weight was 20 kg. The grafts that contained a median of 6.2×10(7) total nucleated cells (TNC)/kg and 2.7×10(5) CD34(+) cells/kg were infused. RESULTS: The median times to neutrophil engraftment and platelet engraftment were 12 days and 25 days, respectively, and the rates of neutrophil engraftment and platelet engraftment were 95% and 78%, respectively. The rate of neutrophil engraftment was positively correlated with the number of CD34(+) cells (P=0.011), while the rate of platelet engraftment was correlated with the numbers of CD34(+) cells and TNC (P=0.001; P=0.014). The incidence rates of acute and chronic graft-versus-host disease were 49% and 11%, respectively. The median follow-up was 54 months. The 5-year transplant-related mortality, overall survival, and disease-free survival were 27%, 57.4% and 41%, respectively. CONCLUSIONS: UCBT is an alternative source of hematopoietic stem cells for patients with hematologic malignancies.