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Bladder cancer is a common urinary tract tumor in clinic, and its morbidity and mortality are always high. Surgical treatment is operator dependent, residual tumor cells often lead to tumor recurrence, and chemotherapy after surgery causes high side effects. So, it is urgent to develop new methods for the theranostics of bladder cancer. Among them, functional nanomaterials have shown good application in tumor theranostics, but they are rarely used in bladder cancer. In our work, we demonstrate the fabrication of folate-modified vincristine-loaded polydopamine-coated Fe3O4 superparticles (Fe3O4@PDA-VCR-FA SPs), and applied them in the theranostics of bladder cancer. The PDA shell not only improves the colloidal stability and biocompatibility, but also enhances the photothermal effect and prolongs the blood circulation half-life. The half-life of Fe3O4@PDA-VCR-FA SPs in blood is calculated as 2.83 h, and the tumor retention rate is 5.96 %ID g-1, these data are significantly higher than those before folic acid modification. The superparamagnetism of Fe3O4 and loading of vincristine endow Fe3O4@PDA-VCR-FA SPs with magnetic resonance imaging and chemotherapy capabilities. Further by employing NIR laser-triggered photothermal therapy, bladder tumors were ablated completely, and no recurrence was observed. Blood and histological tests of the major organs confirm that Fe3O4@PDA-VCR-FA SPs show good biosafety.

In clinical tumor therapy, traditional treatments such as surgery, radiotherapy and chemotherapy all have their own limitations. With the development of nanotechnology, new therapeutic methods based on nanomaterials such as photothermal therapy (PTT) have also emerged. PTT takes advantage of the poor thermal tolerance of tumor cells and uses the heat generated by photothermal reagents to kill tumor cells. A transition metal sulfide represented as Cu2S is an ideal photothermal reagent because of its easy preparation, high extinction coefficient and photothermal conversion efficiency. Surface modification of nanoparticles (NPs) is also necessary, which not only can reduce toxicity and improve colloidal stability, but also can provide the possibility of further chemotherapeutic drug loading. In this work, we report the fabrication of Tween-20 (Tw20)-modified and doxorubicin (Dox)-loaded Cu2S NPs (Cu2S/Dox@Tw20 NPs), which significantly improves the performance in tumor therapy. Apart from the enhancement of colloidal stability and biocompatibility, the drug loading rate of Dox in Tw20 reaches 11.3%. Because of the loading of Dox, Cu2S/Dox@Tw20 NPs exhibit chemotherapeutic behaviors and the tumor inhibition rate is 76.2%. Further combined with a near-infrared laser, the high temperature directly leads to the apoptosis of a large number of tumor cells, while the release of chemotherapeutic drugs under heat can not only continue to kill residual tumor cells, but also inhibit tumor recurrence. Therefore, with the combination of PTT and chemotherapy, the tumor was completely eliminated. Both hematological analysis and histopathological analysis proved that our experiments are safe.

With the rapid growth of livestock breeding, manure composting has evolved to be an important source of atmospheric methane (CH4) which accelerates global warming. Calcium superphosphate (CaSSP), as a commonly used fertilizer, was proposed to be effective in reducing CH4 emissions from manure composting, but the intrinsic biological mechanism remains unknown. Methanogens and methanotrophs both play a key role in mediating CH4 fluxes, therefore we hypothesized that the CaSSP-mediated reduction in CH4 emissions was attributed to the shift of methanogens and methanotrophs, which was regulated by physicochemical parameter changes. To test this hypothesis, a 60-day pig manure windrow composting experiment was conducted to investigate the response of CH4 emissions to CaSSP amendment, with a close linkage to methanogenic and methanotrophic communities. Results showed that CaSSP amendment significantly reduced CH4 emissions by 49.5% compared with the control over the whole composting period. The decreased mcrA gene (encodes the α-subunit of methyl-coenzyme M reductase) abundance in response to CaSSP amendment suggested that the CH4 emissions were reduced primarily due to the suppressed microbial CH4 production. Illumina MiSeq sequencing analysis showed that the overall distribution pattern of methanogenic and methanotrophic communities were significantly affected by CaSSP amendment. Particularly, the relative abundance of Methanosarcina that is known to be a dominant group for CH4 production, significantly decreased by up to 25.3% accompanied with CaSSP addition. Only Type I methanotrophs was detected in our study and Methylocaldum was the dominant methanotrophs in this composting system, in detail, CaSSP amendment increased the relative abundance of OTUs belong to Methylocaldum and Methylobacter. Moreover, the increased SO42− concentration and decreased pH acted as two key factors influencing the methanogenic and methanotrophic composition, with the former has a negative effect on methanogenesis growth and can later promote CH4 oxidation at a low level. This study deepens our understanding of the interaction between abiotic factors, function microbiota and greenhouse gas (GHG) emissions, as well as provides implication for practically reducing composting GHG emissions.

Summary Tertiary lymphoid structure (TLS) provides a local and critical microenvironment for both cellular and humoral immunity and supports effective antigen presentation and lymphocyte activation. However, the gene expression profile and prognostic significance of TLS in oral cancer remain largely unrevealed. In this study, we found the presence of both intratumoral and peritumoral TLSs in a series of 65 patients with oral cancer treated by surgical resection, with positive detection rates of 33.8 and 75.4%, respectively. The presence of intratumoral TLSs, but not peritumoral TLSs, was significantly associated with decreased P53 and Ki67 scores (P = 0·027 and 0·047, respectively). The survival analyses revealed that oral cancer patients with higher grades of TLSs was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·037 and 0·031, respectively). Gene expression profiling analysis of the cytokines and chemokines responsible for lymph-node neogenesis identified a three-up-regulated-gene set, i.e. IL7, LTB and CXCL13, which was shown to be correlated with human oral cancer-associated TLSs. This study provides a framework for better understanding of oral cancer-associated TLSs and for delineating future innovative prognostic biomarkers and immune therapeutic strategies for oral cancer.

Objective This study aims to evaluate the accuracy of magnetic resonance imaging (MRI) in diagnosing orofacial clefts and proposes specific signs for determining the type of cleft. Methods Pregnant women in whom fetal facial malformations are suspected by ultrasonography (US) underwent 1.5 T MRI. The accuracy of the prenatal US and MRI diagnosis was compared with the postnatal findings. Results A total of 71 fetuses were included in the final analysis, which comprised of 35 cases of isolated cleft lip, six cases of cleft lip and alveolus, 21 cases of cleft lip and palate, four cases of isolated cleft palate, and five normal fetuses. MRI was more sensitive than US (MRI 100%, US 77.5%; Fisher's exact test: MRI vs US P=0.000). The accuracy of MRI for all types was 100%. Specific signs (Inverted T, L/anti-L, U, and "Notch" signs) were proposed, indicating the normal hard, unilateral cleft, bilateral cleft, and cleft soft palates, respectively, which can facilitate the identification of different types of cleft palates. Conclusion MRI can accurately diagnose the type of cleft based on typical signs, which can serve as a definite diagnostic modality and an effective supplement of US.

Enhancement of permeability and the retention effect is one of the main pathways for the accumulation of nanomaterials in tumor sites, but poor cellular internalization and rapid clearance of nanomaterials always hamper the efficacy of imaging diagnosis and treatment. With the consideration of both high tumor accumulation and cellular internalization, positively charged nanomaterials can adhere to the tumor cell membrane by an electrostatic force, which is conducive to cellular internalization, but they are easily recognized and cleared during blood circulation. However, negatively charged nanomaterials show an enhanced stealth-like effect and possess a long blood circulation time, which is conducive to tumor accumulation. Therefore, in this work, on the basis of the shielding effect of citrate ions to positive charge and the protonation under an acidic tumor microenvironment, pH-sensitive sodium citrate-modified polyaniline nanoshuttles (NSs) with negative charge during blood circulation but positive charge in tumor sites are designed. With this hierarchical targeting strategy, the blood circulation half-life increases from 4.35 to 7.33 h, and the retention rate of NSs in tumors increases from 5.29 to 8.57% ID/g. Because the retention rate of NSs is increased, the magnetic resonance imaging resolution and signal intensity are significantly improved. A synergistic treatment of tumors is further achieved by means of photothermal therapy with laser irradiation and chemotherapy via heat-stimulated drug release.

The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, the effects of long-term practice on functional network hubs in chess experts are largely undefined. Here, we investigated whether alterations of hubs can be detected in chess experts using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods. We first mapped the whole-brain voxel-wise functional connectivity and calculated the functional connectivity strength (FCS) map in each of the 28 chess players and 27 gender- and age-matched healthy novice players. Whole-brain resting-state functional connectivity analyses for the changed hub areas were conducted to further elucidate the corresponding changes of functional connectivity patterns in chess players. The hub analysis revealed increased FCS in the right posterior fusiform gyrus of the chess players, which was supported by analyses of this area's regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and fractional amplitude of low frequency fluctuations (fALFF). The following functional connectivity analyses revealed increased functional connectivities between the right posterior fusiform gyrus and the visuospatial attention and motor networks in chess players. These findings demonstrate that cognitive expertise has a positive influence on the functions of the brain regions associated with the chess expertise and that increased functional connections might in turn facilitate within and between networks communication for expert behavior to get superior performance.

During the early second trimester, the cortical plate, or “the developing cortex”, undergoes immensely complex and rapid development to complete its major complement of neurons. However, morphological development of the cortical plate and the precise patterning of brain structural covariance networks during this period remain unexplored. In this study, we used 7.0 T high-resolution magnetic resonance images of brain specimens ranging from 14 to 22 gestational weeks to manually segment the cortical plate. Thickness, area expansion, and curvature (i.e., folding) across the cortical plate regions were computed, and correlations of thickness values among different cortical plate regions were measured to analyze fetal cortico-cortical structural covariance throughout development of the early second trimester. The cortical plate displayed significant increases in thickness and expansions in area throughout all regions but changes of curvature in only certain major sulci. The topological architecture and network properties of fetal brain covariance presented immature and inefficient organizations with low degree of integration and high degree of segregation. Altogether, our results provide novel insight on the developmental patterning of cortical plate thickness and the developmental origin of brain network architecture throughout the early second trimester.

Background Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy. Results Herein, we successfully design and construct BiVO4/Fe3O4@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO4 NPs endow BiVO4/Fe3O4@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe3O4 NPs impart BiVO4/Fe3O4@PDA SPs with the superparamagnetic property as a T2-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe3O4 NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO4/Fe3O4@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO4/Fe3O4@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors. Conclusions Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.

ObjectiveThis study was to assess the specific impacts and mechanism of lncRNA GHET1 in the development of triple-negative breast cancer (TNBC).MethodsThe lncRNA GHET1 expression in TNBC tissues and adjacent healthy tissues was detected by qRT-PCR, and its expression was then measured at the cellular level, including TNBC cells and human normal breast epithelial cell line MCF10A. On the completion of transfection of negative shRNA or lncRNA GHET1 shRNA, the TNBC cells, HCC1937 and MDA-MB-468, were then cultured in a normoxia or hypoxia environment, respectively. 5-Ethynyl-2′-deoxyuridine (EdU) assay, colony formation assay, and transwell assay were applicable to the determination of cell proliferation, cell viability, and invasion in each group, respectively. Reagent kits were used for testing glucose consumption and lactate production levels. HCC1937 cells with knockdown or overexpression of lncRNA GHET1 were injected into the nude mice, followed by the examination of resulting tumor volume and weight. The distribution and expression of Hippo/YAP signaling pathway-related proteins were probed using western blotting.ResultsHighly expressed lncRNA GHET1 in TNBC tissues and cells and induction of lncRNA GHET1 by hypoxia were proved. Knockdown of lncRNA GHET1 significantly reduced proliferation, viability, and invasion of TNBC cells, and decreased glucose consumption and lactate production levels under the hypoxia condition. Furthermore, lncRNA GHET1 knockdown decreased HIF-1α expression in hypoxia and significantly inhibited tumor development in vivo. Knockdown of lncRNA GHET1 increased the phosphorylation levels of LATS1 and Yes-associated protein (YAP) to retain YAP within the cytoplasm, while the overexpression of lncRNA GHET1 or hypoxia promoted nuclear translocation of YAP and TNBC development.ConclusionLncRNA GHET1 expression can be induced by hypoxia, which leads to excessive activation of the Hippo/YAP signaling pathway, thus promoting TNBC progression.

The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain.

In this study, the morphological changes in the central sulcus between children with isolated growth hormone deficiency (IGHD) and those with idiopathic short stature (ISS) were analyzed. Thirty children with IGHD (peak growth hormone 5 µg/L) and 30 children with ISS (peak growth hormone 10.0 µg/L) were included. Morphological measurements of the central sulcus were obtained from T1-weighted MRIs using BrainVISA, including the average sulcal width, maximum depth, average depth, top length, bottom length, and depth position-based profiles (DPPs). The bilateral average width of the central sulci was significantly wider, while the left maximum depth and right average depth of the central sulcus were significantly smaller, in children with IGHD than in children with ISS. There were no significant differences in the right maximum depth, left average depth, or bilateral top length and bottom length of the central sulcus between groups. The DPPs of the middle part of both central sulci (corresponding to the hand motor activation area) and the inferior part of the right central sulcus (corresponding to the oral movement area) near the Sylvian fissure were significantly smaller in children with IGHD than in controls before false discovery rate (FDR) correction. However, all the above significant DPP sites disappeared after FDR correction. There were significant morphological changes in the three-dimensional structure of the central sulcus in children with IGHD, which were the outcome of other more essential cortical or subcortical changes, resulting in their relatively slower development in motor, cognitive, and linguistic functional performance.

Numerous behavioral observations and brain function studies have demonstrated that neurological differences exist between East Asians and Westerners. However, the extent to which these factors relate to differences in brain structure is still not clear. As the basis of brain functions, the anatomical differences in brain structure play a primary and critical role in the origination of functional and behavior differences. To investigate the underlying differences in brain structure between the two cultural/ethnic groups, we conducted a comparative study on education-matched right-handed young male adults (age = 22-29 years) from two cohorts, Han Chinese (n = 45) and Caucasians (n = 45), using high-dimensional structural magnetic resonance imaging (MRI) data. Using two well-validated imaging analysis techniques, surface-based morphometry (SBM) and voxel-based morphometry (VBM), we performed a comprehensive vertex-wise morphometric analysis of the brain structures between Chinese and Caucasian cohorts. We identified consistent significant between-group differences in cortical thickness, volume, and surface area in the frontal, temporal, parietal, occipital, and insular lobes as well as the cingulate cortices. The SBM analyses revealed that compared with Caucasians, the Chinese population showed larger cortical structures in the temporal and cingulate regions, and smaller structural measures in the frontal and parietal cortices. The VBM data of the same sample was well-aligned with the SBM findings. Our findings systematically revealed comprehensive brain structural differences between young male Chinese and Caucasians, and provided new neuroanatomical insights to the behavioral and functional distinctions in the two cultural/ethnic populations.

Most of the antitumor chemotherapeutic drugs execute the therapeutic performance upon eliciting tumor cell apoptosis, which may cause chemoresistance of tumors. Design of novel drugs to eradicate apoptosis-resistant tumors via non-apoptotic cell death pathways is promising for improving the long-term chemotherapeutic efficacy. Herein, a Fe(III)-Shikonin metal-polyphenol-coordinated supramolecular nanomedicine for combined therapy of tumor via ferroptosis and necroptosis is designed. The construction of the nanomedicine based on the coordinated self-assembly between Fe3+ and Shikonin not only overcomes the shortcomings of Shikonin including its low bioavailability and high toxicity toward normal tissues, but also integrates the theranostics functions of Fe ions. Under the exposure of the high concentration of glutathione (GSH) in tumor cells, the as-prepared nanomedicine will disassemble into Fe2+ and Shikonin, followed by stimulating the tumor cell death through ferroptosis and necroptosis. In addition, benefiting from the stealth effect of polyethylene glycol (PEG) and the targeting ability of cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) to αv β3 -integrin, NH2 -PEG-cRGD-modified nanomedicine exhibits a GSH-responsive therapy toward 4T1 tumor in vivo and self-enhanced longitudinal relaxation (T1 )-weighted imaging property. Since the self-assembly of natural Shikonin and human body-necessary Fe element is facile and feasible, the work may provide a promising supramolecular nanomedicine for next-generation chemotherapeutic applications.

Indirect nitrous oxide (N2O) emissions from rivers draining agricultural watersheds are of increasing concerns due to riverine abundant sources of nitrogen loaded through leaching and runoff. However, the seasonal variation of N2O emissions from agricultural drainage rivers is poorly explored, especially the uncertainty in quantifying indirect N2O emission factors (EFs) from these aquatic environments. Here, a two-year study (2014-2016) was conducted to quantify indirect N2O emissions from a river draining a rice paddy watershed in subtropical China. Indirect N2O fluxes were simultaneously determined using the floating chamber method (chamber-based) and the gas exchange modeling approach (model-based) based on the measurement of dissolved N2O concentration. Results showed that seasonal dissolved N2O concentration and N2O fluxes had a similar variation pattern, with the highest and the lowest levels in summer and winter, respectively. The annual mean of model-based N2O fluxes (20.24 ± 3.34 μmol m−2 d−1) was generally in agreement with chamber-based N2O fluxes (18.70 ± 3.56 μmol m−2 d−1). The indirect emission factor of N2O was highly dependent on the surface water NO3−-N concentration. Annual mean indirect EF of N2O from the drainage river was estimated to be 0.00051, which was significantly lower than the default EF5r value (0.0025) proposed by the Intergovernmental Panel on Climate Change (IPCC). These results suggest that the use of IPCC default value might have overestimated indirect N2O emissions from agricultural impacted riverine systems. Our study also highlights that more extensive in-situ measurements are required for monitoring indirect N2O emissions from agricultural impacted waters with different drainage characteristics, which would benefit for refining the IPCC EF5r default value to further constrain global N2O budget.

// Fabin Han 1, 6, * , Chao Chen 1, * , Wei Wang 1, * , Hao Song 1 , Sen Li 1 , Jing Duan 1 , Xianjie Lu 1 , Shichao Wu 1 , Nan Zhang 1 , Qingfa Chen 1 , Yan Wang 1 , Shuwei Liu 2 , Chongluo Fu 3 , Chengbiao Lu 4 and Paul Lu 5 1 Centre for Stem Cells and Regenerative Medicine, The Institute for Tissue Engineering & Regenerative Medicine, Liaocheng University/The Liaocheng People’s Hospital, Liaocheng, Shandong, China 2 Department of Human Anatomy, Shandong University, Jinan, Shandong, China 3 College of Biological Science, Liaocheng University, Liaocheng, Shandong, China 4 Department of Neurobiology, Xinxiang Medical College, Xinxiang, Henan, China 5 Department of Neurosciences, University of California at San Diego, La Jolla, CA, USA 6 The Institute for Translational Medicine, The Second Affiliated Hospital, Shandong University, Jinan, Shandong, China * These authors have contributed equally to this work Correspondence to: Fabin Han, email: fhan2013@126.com Keywords: Parkinson's disease; dopamine neuronal differentiation; umbilical cord-derived mesenchymal stromal cell; transplantation; gerotarget Received: July 29, 2017 Accepted: January 01, 2018 Published: January 02, 2018 ABSTRACT Cell therapy have a great potential for the treatment of neurodegenerative disease, such as Parkinson's disease (PD). Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) have been reported to have multipotent differentiation ability. However, the therapeutic impact and mechanisms of dopamine neuronal differentiation from hUC-MSCs in PD are not determined. Here we developed a new protocol to induce dopamine neuron conversion from hUC-MSCs by addition of the growth cocktail containing noggin, CHIR99021, SHH, FGF8, TGFβ, GDNF, and BDNF. Then we transplanted the hUC-MSCs and the growth factor cocktail into the lesion side of the midbrain of 6-OHDA lesioned rat model of PD. The effects of hUC-MSC transplantation on the dopaminergic neuronal differentiation and motor behaviors of the rats were investigated. We found that in the presence of these molecules, the cultured hUC-MSCs showed a high efficient DA neuronal conversion in vitro . In combination with the growth cocktail, grafted hUC-MSCs also showed a highly efficient DA neuronal conversion in the midbrain of 6-OHDA lesioned rats. Both the grafted hUC-MSCs and the differentiated TH-positive neurons survived in 6-OHDA lesioned rats during the post-grafting period of 16 weeks. The hUC-MSCs-derived TH-positive neurons displayed the same electrophysiological profile as DA neurons in vivo . More importantly, rats with transplanted hUC-MSCs showed progressive improvements in motor behaviors compared to controls from weeks 4 to 16 post-grafting. These results demonstrated the efficacy and usefulness of the growth cocktail in combination with hUC-MSC transplantation in 6-OHDA lesioned rats and provided a promising cell-based treatment strategy for the PD patients.

Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

Cancer multimodal treatment by combining the effects of different theranostics agents can efficiently improve treatment efficacy and reduce side effects. In this work, we demonstrate the theranostics nanodevices on the basis of Cu2+-loaded polydopamine nanoparticles (CuPDA NPs), which are able to offer magnetic resonance imaging (MRI)-guided thermochemotherapy (TCT). Systematical studies reveal that after Cu2+ ions loading, the molar extinction coefficient of PDA NPs is greatly enhanced by 4 times, thus improving the performance in photothermal therapy. Despite Cu2+ ions being toxic, the release of Cu2+ is mainly stimulated in acidic environment. Once the NPs deposit in the slightly acidic tumor microenvironment (pH ≈ 6.5–6.8), the release rate boosts ∼30%, which effectively avoids the systematic toxicity during chemotherapy. Meanwhile, due to the increment of the electron–proton dipole–dipole interaction correlation time τC, the spin–lattice relaxation time (T1) for PDA NPs is found to be shortened by Cu...

Chemotherapy is one of the most common and effective ways for the clinical treatment of tumors, but tumor cells develop resistance toward drugs after a long period of chemotherapy. Interestingly, the gene expression of resistant cells usually generates increased sialic acid and raises the negative potential of the cell membranes, which is potentially useful to design novel theranostic models. In this work, we demonstrate multidrug resistant tumors-aimed theranostics by the virtue of the strong electrostatic attraction between resistant cells and nanomaterials. Human oral epithelial carcinoma vincristine-resistant tumor (KBV) and human oral epithelial carcinoma tumor (KB) were employed and compared as the tumor models. Polyethylene glycol-coated and Cu(ii) and vincristine codoped polyaniline nanoshuttles (VCR-PEG-CuPani NSs), which possessed multifunctions, positive charges, and blood circulation half-life of 6.26 ± 0.16 h, were employed as the nanomaterials for performing the tumor theranostics. Because of the stronger electrostatic attraction with KBV than that with KB, VCR-PEG-CuPani NSs showed higher enrichment of 8.05 ± 0.39% ID g-1 for KBV and a lower value of 6.02 ± 0.22% ID g-1 for KB. The higher accumulation of VCR-PEG-CuPani NSs in KBV tumors further improved the efficacy of tumor theranostics, such as those using magnetic resonance imaging, chemotherapy, and photothermal therapy.

Asymmetry has been proved to exist in the human brain structure, function and behavior. Most of the existing brain asymmetry findings are originated from the western populations, while studies about the brain structural and functional asymmetries in East Asians are limited. Extensive evidence suggested that cultural differences, e.g. education and language, may lead to differences in brain structure and function between races. Therefore, we hypothesized that differences in brain structural asymmetries exist between East Asians and Westerners. In this study, we performed a comprehensive surface-based morphometric (SBM) analysis of brain asymmetries in cortical thickness, volume and surface area in two well-matched groups of right-handed, Chinese (n = 45) and Caucasian (n = 45) young male adults (age = 22–29 years). Our results showed consistent inter-hemispheric asymmetries in the three brain morphological measures in multiple brain regions in the Chinese young adults, including the temporal, frontal, parietal, occipital, insular cortices and the cingulate gyrus. Comparing with the Caucasians, the Chinese group showed greater structural asymmetry in the frontal, temporal, occipital and insular cortices, and smaller asymmetry in the parietal cortex and cingulate gyrus. These findings could provide a new neuroanatomical basis for understanding the distinctions between East Asian and Caucasian in brain functional lateralization.

To date, there is an urgent need for cancer treatment to improve in many ways in order to successfully cure all cancers. Retinoic acid (RA) is a promising anti-cancer drug through influencing cancer stem cells (CSCs). Taxol is a chemotherapy drug for many cancers. To increase the anti-cancer effects of RA and taxol, we created a novel RA nanoparticle, FCRAN, which has the ability of carrying a second anti-cancer drug, taxol, using nanotechnological methods. The results of this study demonstrated that this RA nanoparticle was water-soluble and retained the same effects as RA on cancer cells, such as inhibiting the proliferation of CSCs, inducing the differentiation of CSCs, and enhancing the sensitivity of CSCs to chemotherapeutic drugs. In addition, this RA nanoparticle can be used to carry a second anticancer drug, taxol, to become FCRAN/T and synergistically enhance the anti-cancer effects of both drugs in vivo. Interestingly, the FCRAN/T is a targetable anti-cancer nanoparticle in the presence of higher levels of glutathione (GSH) in cancer cells. Our results demonstrate that our novel synthesized nanoparticles not only retain the RA functions, but can also carry a second anticancer drug to play a synergistic anticancer role with good water solubility, in particular FCRAN/T can target cancer cells. Therefore, our novel synthesized targetable anti-cancer nanoparticles have a better application prospect than that of RA or taxol alone.

The growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis plays an important role in normal brain development, and GH deficiency inevitably affects the growth of the cerebral cortex. This study was designed to analyze morphological differences in gray matter volume, cortical surface area, and gray matter thickness between children with isolated growth hormone deficiency (IGHD) and children with idiopathic short stature (ISS). Twenty-four children with IGHD (mean age 9.42 years, peak GH 5 μg/l) and 24 controls with ISS (mean age 9.21 years, peak GH 10 μg/l) were included. High-resolution three-dimensional T1-weighted MRIs were acquired at participants' first visit. Measurements of gray matter volume, cortical surface area and gray matter thickness were obtained using FreeSurfer. The total and regional differences between groups were statistically analyzed. Correlations between the FreeSurfer results and GH and IGF-I levels were also obtained. The gray matter volume, cortical surface area and gray matter thickness of the total brain and of the bilateral hemispheres of children with IGHD were significantly smaller than those of children with ISS (all P values 0.05). All the measurements had similar cortical distributions between groups but varied across regions. Cortical regions with significant differences in the mean gray matter volume and surface area were mainly distributed around the bilateral central sulci and the lateral and basal parts of the temporal lobes (all P values 0.05). There were negative correlations between gray matter volume, cortical surface area and GH levels, and the right hemispheric and total cortical surface area correlated significantly with GH levels (all P values 0.05) in children with IGHD. There were significant positive correlations between gray matter volume, cortical surface area and IGF-I levels (all P values 0.05) in both groups, except for in left hemispheric gray matter volume in children with ISS. Children with IGHD have significant morphological changes in the cerebral cortex, which were partially influenced by GH and IGF-I levels. These cortical changes may be related to deficits in their relatively slower development in intelligence, motor performance, and other functions.

During the 3(rd) trimester, dramatic structural changes take place in the human brain, underlying the neural circuit formation. The survival rate of premature infants has increased significantly in recent years. The large morphological differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the brain at 40PMW (full term) make it necessary to establish age-specific atlases for preterm brains. In this study, with high quality (1.5×1.5×1.6mm(3) imaging resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm and term-born neonates, we established age-specific preterm and term-born brain templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a single-subject template, a population-averaged template with linear transformation and a population-averaged template with nonlinear transformation. Each of the age-specific DTI atlases includes comprehensive labeling of 126 major gray matter (GM) and white matter (WM) structures, specifically 52 cerebral cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic morphological changes of delineated individual neural structures such as ganglionic eminence and uncinate fasciculus were revealed. The evaluation based on measurements of Dice ratio and L1 error suggested reliable and reproducible automated labels from the age-matched atlases compared to labels from manual delineation. Applying these atlases to automatically and effectively delineate microstructural changes of major WM tracts during the 3(rd) trimester was demonstrated. The established age-specific DTI templates and atlases of 33, 36 and 39 PMW brains may be used for not only understanding the complicated yet precisely organized functional and structural maturational processes but also detecting neural disorder biomarkers of the preterm brains as clinical references.

Agricultural nitrate leaching and runoff incurs high nitrogen loads in agricultural irrigation watersheds, constituting one of important sources of atmospheric nitrous oxide (N2O). Two independent sampling campaigns of N2O flux measurement over diel cycles and N2O flux measurements once a week over annual cycles were carried out in an agricultural irrigation watershed in southeast China using floating chamber (chamber-based) and gas transfer equation (model-based) methods. The diel and seasonal patterns of N2O fluxes did not differ between the two measurement methods. The diel variation in N2O fluxes was characterized by the pattern that N2O fluxes were greater during nighttime than daytime periods with a single flux peak at midnight. The diel variation in N2O fluxes was closely associated with water environment and chemistry. The time interval of 9:00–11:00 a.m. was identified to be the sampling time best representing daily N2O flux measurements in agricultural irrigation watersheds. Seasonal N2O fluxes showed large variation, with some flux peaks corresponding to agricultural irrigation and drainage episodes and heavy rainfall during the crop-growing period of May to November. On average, N2O fluxes calculated by model-based methods were 27% lower than those determined by the chamber-based techniques over diel or annual cycles. Overall, more measurement campaigns are highly needed to assess regional agricultural N2O budget with low uncertainties.

Qiaowen Yu,1 Qisen Guo,2 Liangan Chen,3 Shuwei Liu1 1Shandong Provincial Key Laboratory of Mental Disorders, Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, 2Respiratory Medicine, Shandong Cancer Hospital, Jinan, 3Department of Respiratory Diseases, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Background: CDH1 is a protein encoded by the CDH1 gene in humans. Mutations in this gene are linked with several types of cancer. Loss of CDH1 function contributes to the progression of cancer by increasing proliferation, invasion, and/or metastasis. However, the association between and clinicopathological significance of CDH1 promoter methylation and lung cancer remains unclear. In this study, we systematically reviewed the studies of CDH1 promoter methylation and lung cancer, and evaluated the association between CDH1 promoter methylation and lung cancer using meta-analysis methods.Methods: A comprehensive search of the PubMed and Embase databases was performed up to July 2014. The methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized.Results: Finally, an analysis of 866 patients with non-small cell lung cancer from 13 eligible studies was performed. The CDH1 methylation level in the cancer group was significantly higher than in the controls (OR 3.89, 95% confidence interval [CI] 2.87–5.27, P

To identify and justify the best section to reveal each segment of the abducens nerve according to 3D-SPACE magnetic resonance sequences and correlate with cryosectional specimens.Thirty-four healthy adults were recruited for MRI using a 3D-SPACE sequence. Eighteen adult head specimens were cut into serial transverse, sagittal and coronal section using an electric band saw after the specimens were frozen. The MRI characteristics and the anatomical features of the abducens nerve were analyzed by correlation with the cryosection.We divided the abducens nerve into five segments, the cisternal segment, Dorello canal (DC) segment, cavernous sinus (CS) segment, superior orbital fissure (SOF) segment and intraorbital segment. In the transverse sections, the detection rates for the cisternal and Dorello canal segments of the abducens nerve were 97.06 and 94.12 %, respectively, on 3D-SPACE MR images. In the sagittal section of the frozen specimens, only the cisternal segment of the abducens nerve could be observed, and its detection rate was 51.50 %. In the coronal section, the CS segment of the abducens nerve was located inferior lateral to the ICA as well as, inferior to the oculomotor and trochlear nerves, and the detection rate of the CS segment was 42.60 % on 3D-SPACE MR images.3D-SPACE sequence MR scanning was a useful method for observing the cisternal and DC segment of the abducens nerve in a transverse section, observing the cisternal segment in a sagittal section and observing the CS segment in a coronal section.

Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage.

Morphological observation and measurements of endocasts have played a vital role in research on the evolution of the human brain. However, endocasts have never been used to investigate how the human brain has evolved since the Neolithic period. We investigated the evolution of the human brain during the Holocene by comparing virtual endocasts from Beiqian site (a Neolithic Chinese site) and a sample of Chinese modern-day humans. Standardized measurements and indices were taken to provide quantification of the overall endocast shape, including the length, breadth, height, frontal breadth, and the ratio of frontal breadth to breadth, as well as the cranial capacity. We found that the height of the endocasts and cranial capacity have decreased between our two samples, whereas the frontal breadth and sexual dimorphism have increased. We argue that these changes can be caused by random genetic mutation and epigenetic change in response to changes in the environment. Am J Phys Anthropol 154:94–103, 2014. © 2014 Wiley Periodicals, Inc.

Few investigators have analyzed fetal ocular growth with Magnetic Resonance Imaging (MRI) of high magnetic strength. Our purpose is to obtain normative biometrics for fetal ocular development in the second trimester of pregnancy. Sixty specimens with a gestational age (GA) of 12-23 weeks were scanned using a 7.0 T MRI scanner. The linear interocular and binocular distances (IOD and BOD, respectively), globe diameter (GD) and lens diameter (LD) were measured on the transverse section of the largest diameter of the eyeballs. The three dimensional (3D) visualization model of the eyeball was reconstructed with Amira software. Then, the globe and lens volumes (GV and LV, respectively) were obtained. All the measurements were plotted as a function of GA. The fetal ocular structures in the second trimester of pregnancy could be clearly delineated on 7.0 T postmortem MRI images. All the linear measurements logarithmically increased with GA, while, the volumetric measurements linearly increased with GA. Postmortem MRI of high magnetic strength can clearly document fetal ocular growth in the second trimester of pregnancy. These quantitative data may be a valuable reference for the assessment of normal fetal eyeball development in clinical settings and may be considered a supplement to anatomical investigations.

During the second trimester, the human fetal brain undergoes numerous changes that lead to substantial variation in the neonatal in terms of its morphology and tissue types. As fetal MRI is more and more widely used for studying the human brain development during this period, a spatiotemporal atlas becomes necessary for characterizing the dynamic structural changes. In this study, 34 postmortem human fetal brains with gestational ages ranging from 15 to 22 weeks were scanned using 7.0 T MR. We used automated morphometrics, tensor-based morphometry and surface modeling techniques to analyze the data. Spatiotemporal atlases of each week and the overall atlas covering the whole period with high resolution and contrast were created. These atlases were used for the analysis of age-specific shape changes during this period, including development of the cerebral wall, lateral ventricles, Sylvian fissure, and growth direction based on local surface measurements. Our findings indicate that growth of the subplate zone is especially striking and is the main cause for the lamination pattern changes. Changes in the cortex around Sylvian fissure demonstrate that cortical growth may be one of the mechanisms for gyration. Surface deformation mapping, revealed by local shape analysis, indicates that there is global anterior–posterior growth pattern, with frontal and temporal lobes developing relatively quickly during this period. Our results are valuable for understanding the normal brain development trajectories and anatomical characteristics. These week-by-week fetal brain atlases can be used as reference in in vivo studies, and may facilitate the quantification of fetal brain development across space and time.

To investigate the fetal cerebral lobes development between 20 and 28 weeks gestational age, 36 fetus specimen without CNS abnormality, with 4 fetuses in each gestation week, were scanned with 3.0T MR. Lobular parameters were measured, including the parenchyma thickness of the frontoparietal and the temporal lobes, the margin length of frontoparietal, the insula and the temporal lobes, the Sylvian fissure and the perimeter of hippocampus, on the plane perpendicular to the longitudinal axis of hippocampus body across the base of cerebral peduncle. The relative value of parenchyma thickness and the lobes' length ratios to the same side hemisphere were calculated and their correlation with gestational weeks was analyzed. All measured parameters were positively correlated with gestational age. No significant tendency was found for relative value of the parenchyma thickness (P0.05). The temporal lobe length ratio increased while the frontoparietal ratio decreased before 24 weeks GA and then the two reversed. The Sylvian fissure length ratio increased (P0.001) and the hippocampus decreased (P0.001) throughout this period. In conclusion, the early fetal cerebrum lobes developed asynchronously during this period, the 24 weeks GA could be a turning point for cerebrum development pattern changing from primitive to mature.

This study aims to investigate metabolic changes in frontal and parietal cortices in the 6-OHDA induced Parkinson's rats. Ratios of N-acetyl-aspartic acid/creatine (NAA/Cr), choline/creatine (Cho/Cr), and glumatic acid and glutamine glutaminic acid/creatine (Glx/Cr) of regions of interests (ROIs) in the frontal and parietal cortices, and the substantia nigra were analyzed. NAA/Cr, Cho/Cr and Glx/Cr in the frontal and parietal cortices in the lesion side did not show any significant differences two weeks after operation compared with the contralateral side (p > 0.05). NAA/Cr in the frontal cortex in the lesion side was significantly lower in the five weeks after operation; Cho/Cr remained normal; Glx/Cr increased (p < 0.05), and all ratios of parietal cortex were normal. In the eight weeks after operation, NAA/Cr in the frontal cortex in the lesion side was lower than that of the five weeks (p < 0.01), Cho/Cr still remained normal while Glx/Cr was higher than before (p < 0.01). Regarding the parietal cortex, NAA/Cr increased significantly, while Cho/Cr and Glx/Cr remained normal. In the 12 weeks after operation, NAA/Cr, Cho/Cr and Glx/Cr in frontal cortex were consistent with that of the eight weeks, while they remained at the normal level in parietal cortex. The NAA/Cr in the substantia nigra decreased and Cho/Cr increased significantly during 2-8 weeks, and remained at the same level during 8-12 weeks. There are metabolic disturbances in PD rats. The transient hyperfunction in the parietal cortex can be considered as a compensation for the dysfunction of the frontal cortex and substantia nigra.

The visualization of intersegmental planes was closely related to their thickness, and the difference of thickness between two types of intersegmental planes was congenital.

Functional neuroimaging studies have indicated the involvement of separate brain areas in three distinct attention systems: alerting, orienting, and executive control (EC). However, the structural correlates underlying attention remains unexplored. Here, we utilized graph theory to examine the neuroanatomical substrates of the three attention systems measured by attention network test (ANT) in 65 healthy subjects. White matter connectivity, assessed with diffusion tensor imaging deterministic tractography was modeled as a structural network comprising 90 nodes defined by the automated anatomical labeling (AAL) template. Linear regression analyses were conducted to explore the relationship between topological parameters and the three attentional effects. We found a significant positive correlation between EC function and global efficiency of the whole brain network. At the regional level, node-specific correlations were discovered between regional efficiency and all three ANT components, including dorsolateral superior frontal gyrus, thalamus and parahippocampal gyrus for EC, thalamus and inferior parietal gyrus for alerting, and paracentral lobule and inferior occipital gyrus for orienting. Our findings highlight the fundamental architecture of interregional structural connectivity involved in attention and could provide new insights into the anatomical basis underlying human behavior.

We hypothesized that the distinct maturational processes take place across different cortical areas from middle fetal stage to normal time of birth and these maturational processes are altered in late third trimester. Fractional anisotropies (FA) from diffusion tensor imaging (DTI) infer the microstructures of the early developing cortical plate. High-resolution DTI of 11 fetal brain specimens at postmenstrual age of 20 weeks (or simplified as 20 weeks), 19 in vivo brains at 35 weeks, and 17 in vivo brains at normal time of birth at term (40 weeks) were acquired. Population-averaged age-specific DTI templates were established with large deformation diffeomorphic metric mapping for subject groups at 20, 35, and 40 weeks. To alleviate partial volume effects, skeletonized FA values were used for mapping averaged cortical FA to the cortical surface and measuring FA at 12 functionally distinctive cortical regions. Significant and heterogeneous FA decreases take place in distinct cortical areas from 20 to 35 weeks and from 35 to 40 weeks, suggesting differentiated cortical development patterns. Temporally nonuniform FA decrease patterns during 35-40 weeks compared with those during 20-35 weeks were observed in higher-order association cortex. Measured skeletonized FA suggested dissociated changes between cerebral cortex and white matter during 35-40 weeks.

Objective The computerized freezing milling technique is derived from the virtual human project. It has been widely used in three-dimensional (3D) reconstruction of the human body and organs. With this technique, the study was undertaken to explore the 3D features and adjacent anatomic relationships of the sellar region for skull base surgery. Methods Continuous thin sections on the coronary plane were performed with the computerized freezing milling technique using a human head specimen. The related structures were described in six sections. After segmenting, labeling, and extracting in serial sections, the 3D reconstruction of the sellar region was finished with Amira 4.1 software. Results A total of 390 thin coronary sections were obtained. In six sections, the anatomic relationships of the pituitary gland, carotid artery, sphenoid sinus, and nerves are displayed. Three-dimensional images of the sellar region are video films that continuously and dynamically display anatomic structures in 3D space at different velocities. It can show that the cavernous segment of the internal carotid artery is located anterolateral to the sphenoid sinus and lateral to the pituitary gland. The optic nerve protrudes into the superolateral portion of the sphenoid sinus. Conclusions The combination of coronary sectional anatomy and 3D reconstruction can display the anatomic characteristics of the sellar region. The 3D models are video films that continuously and dynamically display anatomic structures in 3D space at different velocities.

This study aims to obtain the signal intensity changes and quantitative measurements of the subcortical brain structures of 12-22 weeks gestational age (GA).Sixty-nine fetal specimens were selected and scanned by 7.0-T MR. The signal intensity changes of the subcortical brain structures were analyzed. The three-dimensional visualization models of the germinal matrix, caudate nucleus, lentiform nucleus, and dorsal thalamus were rebuilt with Amira 4.1, and the developmental trends between the measurements and GA were analyzed.The germinal matrix was delineated on 7.0-T MR images at 12 weeks GA, with high signals on T1-weighted images (WI). While at 16 weeks GA, the caudate nucleus, lentiform nucleus, and internal and external capsules could be distinguished. The caudate nucleus was high signal intensity on T1WI. The signal intensity of the putamen was high on T1WI during 15-17 weeks GA and was delineated as an area with uneven signal intensities. The signal intensity of the peripheral area of the putamen became higher after 18 weeks GA. The signal intensity of the globus pallidus was high on T1WI and low on T2WI after 20 weeks GA. At 18 weeks GA, the claustrum was delineated with low signals on T2WI. Measurements of the germinal matrix, caudate nucleus, lentiform nucleus, and dorsal thalamus linearly increased with the GA.Development of the subcortical brain structures during 12-22 weeks GA could be displayed with 7.0-T MRI. The measurement provides significant reference beneficial to the clinical evaluation of fetal brain development.

The Visible Human Projects, which were launched in the United States, have also been developed in Korea and China during the past decade. This article includes the new trials to promote a variety of their applications. In a Korean laboratory, whole bodies of two cadavers were serially sectioned (Visible Korean), while two Chinese institutes have sectioned nine cadavers (Chinese Visible Human and Virtual Chinese Human). For acquiring sectioned images and stereoscopic models of better quality, appropriate cadavers were chosen; equipments and techniques for embedding, sectioning, photography, and computer processing were continuously improved in the two countries. To facilitate the research, Korean and Chinese scientists have visited each other. The sectioned images with thinner intervals (0.2 mm or less) and higher resolution were obtained. From the advanced data, the segmented images of comprehensive structures were prepared to construct three-dimensional models. Then, cross-sectional images and models were offered for medical education and clinical practice such as electronic anatomy atlas and virtual lumbar puncture. Every project has its strengths and weaknesses with regard to the image data; users in the world can choose the project that best suits their needs.

article i nfo Mammalian target of rapamycin (mTOR) pathway is a serine/threonine protein kinase that plays a vital role in regulating growth, proliferation, survival, and protein synthesis among cells. In the present study, we in- vestigated the role of the mTOR pathway following subarachnoid hemorrhage brain injury — specifically in- vestigating its ability to mediate the activation of cerebral vasospasm. Additionally, we investigated whether key signaling pathway molecules such as the mTOR, P70S6K1, and 4E-BP1 play a role in the process. Thirty dogs were randomly divided into 5 groups: sham, SAH (subarachnoid hemorrhage), SAH+DMSO (dimethyl sulfoxide), SAH+Rapamycin and SAH+AZD8055. An established canine double-hemorrhage model of SAH was used by injecting autologous arterial blood into the cisterna magna on days 0 and 2. Angiography was performed at days 0 and 7. Clinical behavior, histology, immunohistochemistry, and Western blot of mTOR, P70S6K1, 4E-BP1 and PCNA (proliferating cell nuclear antigen) in the basilar arteries were examined. In the SAH and SAH+DMSO groups, severe angiographic vasospasm was obtained (34.3±19.8%, 38.4±10.3) compared with that in Sham (93.9±5.0%) respectively. mTOR, P70S6K1, 4E-BP1 and PCNA increased in the sample of spastic basilar arteries (pb0.05). In the SAH+RAPA and SAH+AZD8055 groups, Rapamycin and AZD8055 attenuated angiographic vasospasm (62.3±15.9% and 65.2±10.3%) while improving appetite and activity scores (pb0.05) on days 5 through 7. Rapamycin and AZD8055 significantly reduced the level and expression of mTOR, P70S6K1, 4E-BP1 and PCNA (pb0.05). In conclusion, our study suggests that the mTOR molecular signaling pathway plays a significant role in cerebral vasospasm following SAH, and that in- hibition of the mTOR pathway has the potential to become an attractive strategy to treat vasospasm following SAH.

Background The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA. Objective To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model. Materials and methods 20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1. Results Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found. Conclusions The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.

The cerebellum is one of the most important structures in the posterior cranial fossa, but the characterization of its development by magnetic resonance imaging (MRI) is incomplete. We scanned 40 fetuses that had no morphological brain disorder at 14-22 weeks of gestation using 7.0 T MRI. Amira 4.1 software was used to determine morphological parameters of the fetal cerebellum, which included the cerebellar volume (CV), transverse cerebellar diameter (TCD), and the length and width of the vermis. The relationship between these measurements and gestational age (GA) was analysed. We found that the primary fissure was visible at week 14 of gestation. From week 16, the prepyramidal fissure, the secondary fissure and the dentate nucleus could be identified. The posterolateral fissure and the fourth ventricle were recognized at week 17, whereas the tentorium of the cerebellum was visible at week 20. The relationships between GA and CV, TCD, and the width and length of the vermis were described adequately by second-order polynomial regression curves. The ratios between TCD and vermis length and between TCD and vermis width decreased with GA. These results show that 7.0 T MRI can show the trajectory of cerebellar development clearly. They increase our understanding of normal cerebellar development in the fetus, and will facilitate the diagnosis of pathological intrauterine changes in the cerebellum.

In this study, scalar values for the fetal brain from 12 to 20 weeks gestational age were obtained. Fifty-two fetal specimens of 12–20 weeks gestational age with an anatomically normal and developmentally appropriate central nervous system (CNS) were scanned using a 7.0 T magnetic resonance imaging (MRI) scanner. The linear biometric measurements of the brain were then determined. All the measurements (except for the interhemispheric distance) were found to increase linearly with gestational age, although each increased at a different growth rates. The 95% confidence interval for each value was obtained. These data may be considered to be a valuable reference for the assessment of normal fetal brain development in clinical settings and as a supplement to post-mortem MRI or anatomical investigations.

In recent years, investigations of the pathologic mechanism of Parkinson's disease (PD) have mainly concentrated on the basal ganglia. However, recent studies have confirmed that pathological changes in PD are accompanied by functional motor changes of the cerebral cortex. Rats were injected with 6-hydroxydopamine and ascorbic acid in the right substantia nigra. In this rat model of PD, magnetic resonance spectroscopy showed the ratio of N-acetyl-aspartic acid to creatine in a lesion in the right frontal cortex was significantly lower than the same ratio in a control group of rats. The ratio of choline to creatine in a lesion in the right frontal cortex was not significantly different between the PD-model rats and control rats. In addition, the optical densities of neurofilament protein and synaptophysin positive sites decreased significantly on the side of the brain with the injury compared with the side without the injury, and with both sides in the control rats. The density of synapses in the frontal cortex on the lesioned side was decreased compared with the unlesioned side. There were abnormal changes in the presynaptic membrane. postsynaptic membrane and synaptic vesicles, and the typical synaptic structure was no longer apparent on the lesioned side. We hypothesized loss of neurons and synapses, abnormal synaptic structure and neuron and synaptic dysfunction of the frontal cortex with a lesion in the injury side of the frontal cortex in PD-model rats. These changes might have an important role in the pathologic mechanism of PD. (C) 2009 Elsevier Ltd. All rights reserved.

Alpha-synuclein is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease. Mutation or overexpression of alpha-synuclein causes Parkinson's disease, and downregulation of alpha-synuclein resists MPP(+)-induced cell death, but the mechanism remains elusive. In this study, we attempted to explore the effect of alpha-synuclein knockdown on mitochondrial function in MPP(+)-treated SH-SY5Y cells. We reconstructed the short hairpin RNA expression vector, pGenesil-2, specially targeting alpha-synuclein mRNA, and it was stably transfected into SH-SY5Y cells. Cell viability, nuclear morphology, and mitochondrial membrane potential were then detected, and the expression of alpha-synuclein, cytochrome c, Bcl-2 and Bax were analyzed by Western blotting. The results showed that after exposure to 500 microM MPP(+) for 24 h, about 41.0+/-1.5% control cells showed low mitochondrial membrane potential. However, the percentage was 13.6+/-1.2% in MPP(+) treated alpha-synuclein knockdown cells. MPP(+) induced cytochrome c release significantly, which was about 3.1-fold compared with that of control. However, in alpha-synuclein knockdown cells, the release of cytochrome c was blocked, which was about 1.4-fold compared with that of control. The Bcl-2/Bax ratio of SH-SY5Y cells reduced to 35.5+/-3.8% after MPP(+) treatment, and this ratio was 85.2+/-3.0% in MPP(+) treated alpha-synuclein knockdown cells. These data suggest that knockdown of alpha- synuclein might be an effective means in rescuing MPP(+)-induced mitochondrial dysfunction of SH-SY5Y cells.