Neonicotinoid insecticides (NEOs) are widely used around the world. The distribution of NEOs in paired saliva and periodontal blood samples was not previously documented in China. In this study, the ...concentrations of six NEOs and three corresponding metabolites were measured in 188 paired saliva and periodontal blood samples collected from South China. NEOs and their metabolites were frequently detected (68–94%) in paired saliva and periodontal blood, with median levels of 0.01–0.99 ng/mL. 1-Methyl-3-(tetrahydro-3-furylmethyl) urea was the most predominant NEO in paired saliva (39%) and periodontal blood (42%). Gender-related differences in NEOs and their metabolite concentrations were found: males showed lower levels than females. We calculated the concentration ratios between saliva and periodontal blood (S/PB ratios), and found that the median S/PB ratios of NEO and their metabolites were higher than 1, indicating that NEOs and their metabolites were easily excreted via saliva. 8-Hydroxy-2’-deoxyguanosine (8-OHdG) was measured in paired saliva and periodontal blood as a marker of oxidative stress. 8-OHdG concentrations in saliva and periodontal blood were significantly and positively correlated (p < 0.05) with the concentrations of most NEOs and their metabolites in saliva and periodontal blood samples. These findings indicated that exposure to NEOs and their metabolites is associated with oxidative stress. This study is the first to report NEOs and their metabolites in paired saliva and periodontal blood samples collected from South China.
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•First study of levels of neonicotinoids (NEOs) in paired saliva and periodontal blood samples.•1-Methyl-3-(tetrahydro-3-furylmethyl) urea was the most predominant NEOs in paired samples.•Higher levels of NEOs in paired samples were found in females than those in males.•Levels of NEOs in paired samples were positively associated with 8-Hydroxy-2’-deoxyguanosine.
Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box ...protein TBR2/EOMES is preferentially enriched in intermediate progenitors and supports cortical neurogenesis expansion. Here we show that TBR2 regulates fine-scale spatial and circuit organization of excitatory neurons in addition to enhancing neurogenesis in the mouse cortex. TBR2 removal leads to a significant reduction in neuronal, but not glial, output of individual radial glial progenitors as revealed by mosaic analysis with double markers. Moreover, in the absence of TBR2, clonally related excitatory neurons become more laterally dispersed and their preferential synapse development is impaired. Interestingly, TBR2 directly regulates the expression of Protocadherin 19 (PCDH19), and simultaneous PCDH19 expression rescues neurogenesis and neuronal organization defects caused by TBR2 removal. Together, these results suggest that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly via PCDH19 in the mammalian cortex.
Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem ...cell-like glioma cells (SCLGC) to support tumor angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and xenografts potently generated tumors when implanted into the brains of immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC were morphologically distinguishable from non-SCLGC tumor populations by widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential molecular mechanism for SCLGC in angiogenesis, we measured the expression of a panel of angiogenic factors secreted by SCLGC. In comparison with matched non-SCLGC populations, SCLGC consistently secreted markedly elevated levels of vascular endothelial growth factor (VEGF), which were further induced by hypoxia. In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly increased endothelial cell migration and tube formation compared with non-SCLGC tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on endothelial cells were specifically abolished by the anti-VEGF neutralizing antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore, bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed growth of xenografts derived from SCLGC but limited efficacy against xenografts derived from a matched non-SCLGC population. Together these data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting proangiogenic factors from stem cell-like tumor populations may be critical for patient therapy.
On the exactness of soft theorems Guerrieri, Andrea L.; Huang, Yu-tin; Li, Zhizhong ...
The journal of high energy physics,
12/2017, Volume:
2017, Issue:
12
Journal Article
Peer reviewed
Open access
A
bstract
Soft behaviours of S-matrix for massless theories reflect the underlying symmetry principle that enforces its masslessness. As an expansion in soft momenta, sub-leading soft theorems can ...arise either due to (I) unique structure of the fundamental vertex or (II) presence of enhanced broken-symmetries. While the former is expected to be modified by infrared or ultraviolet divergences, the latter should remain exact to all orders in perturbation theory. Using current algebra, we clarify such distinction for spontaneously broken (super) Poincaré and (super) conformal symmetry. We compute the UV divergences of DBI, conformal DBI, and A-V theory to verify the exactness of type (II) soft theorems, while type (I) are shown to be broken and the soft-modifying higher-dimensional operators are identified. As further evidence for the exactness of type (II) soft theorems, we consider the
α
′ expansion of both super and bosonic open strings amplitudes, and verify the validity of the translation symmetry breaking soft-theorems up to
O
α
′
6
. Thus the massless S-matrix of string theory “knows” about the presence of D-branes.
The mechanical properties of resin samples in low-force stereolithography additive manufacturing were affected by the printing orientation, and were investigated and optimized to achieve excellent ...single or comprehensive tensile strength, compressive strength, and flexural modulus. The resin samples were fabricated using a Form3 3D printer based on light curing technology according to the corresponding national standards, and they were detected using a universal testing machine to test their mechanical properties. The influence of the printing orientation was represented by the rotation angle of the resin samples relative to the x–axis, y–axis and z–axis, and the parameters was selected in the range 0°–90° with an interval of 30°. The multiple regression models for the mechanical properties of the prepared resin samples were obtained based on least square estimation, which offered a foundation from which to optimize the parameters of the printing orientation by cuckoo search algorithm. The optimal parameters for the tensile strength, compressive strength and flexural modulus were ‘α = 45°, β = 25°, γ = 90°’, ‘β = 0°, β = 51°, γ = 85°’ and ‘α = 26°, β = 0°, γ = 90°’, respectively, which obtained the improvements of 80.52%, 15.94%, and 48.85%, respectively, relative to the worst conditions. The mechanism was qualitatively discussed based on the force analysis. The achievements obtained in this study proved that optimization of the printing orientation could improve the mechanical properties of the fabricated sample, which provided a reference for all additive manufacturing methods.
Considering the situation and disadvantages of being physically inactive as well as the nature and advantages of doing physical exercise regularly, there is a need to explore how physical exercise ...habits are cultivated and formed. The study was to examine the formation process of physical exercise habits. According to the Model of Physical Exercise and Habit, It was speculated that satisfaction, demand or chain from satisfaction to demand could mediate the relationship between physical exercise behavior and physical exercise habit. Cross-sectional design with 3202 college or university students from China was employed. Data about physical exercise habits, physical exercise behaviors as well as related questions was measured by the Self-Report Exercise Habits Index and direct questions. Structural Equation Modeling (SEM) was constructed to evaluate the mediating effects of demand and/or satisfaction by Asymptotically Distribution-Free and BOOTSTRAP. The inferential statistics was to estimate path coefficient and mediation effect. Findings suggested physical exercise behaviors could develop into physical exercise habits through a direct path, single mediators of demand or satisfaction, or a chain mediator from demand to satisfaction.
Long noncoding RNAs (lncRNAs) have been identified to have increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. Recent studies have demonstrated ...that lncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is decreased in several cancers; however, the role of NBR2 in the development of osteosarcoma has not been elucidated. In our study, we found that NBR2 expression was downregulated in osteosarcoma tissues, and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall survival time compared with those with higher NBR2 expression. NBR2 overexpression inhibited osteosarcoma cell proliferation, invasion, and migration but did not increase apoptosis. Furthermore, RNA‐binding protein immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein. Furthermore, overexpression of Notch1 in NBR2‐overexpressing osteosarcoma cells reversed the effects of NBR2 on cell proliferation, invasion, migration, and epithelial‐mesenchymal transition. The in vivo results showed that NBR2 overexpression inhibited tumor growth in nude mice that were inoculated with osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA) expression of Notch1, N‐cadherin, and vimentin and increased the mRNA expression of E‐cadherin in the tumor tissues. These data indicated that NBR2 served as a tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell proliferation, invasion, and migration. The current study provides a novel insight and treatment strategy for osteosarcoma.
NBR2 (neighbor of BRCA1 gene 2) expression was downregulated in osteosarcoma tissues and cell lines; and lower NBR2 expression indicated a shorter overall survival time. Overexpression of NBR2 inhibited osteosarcoma cell proliferation, invasion, and cell migration. Ectopic expression of NBR2 reduced the expression levels of Notch1 signaling‐dependent epithelial‐mesenchymal transition (EMT).
Malignant gliomas rank among the most lethal cancers. Gliomas display a striking cellular heterogeneity with a hierarchy of differentiation states. Recent studies support the existence of cancer stem ...cells in gliomas that are functionally defined by their capacity for extensive self-renewal and formation of secondary tumors that phenocopy the original tumors. As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells.
Based on previous methods that we and others have employed, tumor cell populations were enriched or depleted for cancer stem cells using the stem cell marker CD133 (Prominin-1). We characterized c-Myc expression in matched tumor cell populations using real time PCR, immunoblotting, immunofluorescence and flow cytometry. Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. To interrogate the significance of c-Myc expression in glioma cancer stem cells, we targeted its expression using lentivirally transduced short hairpin RNA (shRNA). Knockdown of c-Myc in glioma cancer stem cells reduced proliferation with concomitant cell cycle arrest in the G(0)/G(1) phase and increased apoptosis. Non-stem glioma cells displayed limited dependence on c-Myc expression for survival and proliferation. Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when xenotransplanted into the brains of immunocompromised mice.
These findings support a central role of c-Myc in regulating proliferation and survival of glioma cancer stem cells. Targeting core stem cell pathways may offer improved therapeutic approaches for advanced cancers.
Malignant gliomas are lethal cancers that display striking cellular heterogeneity. A highly tumorigenic glioma tumor subpopulation, termed cancer stem cells or tumor-initiating cells, promotes ...therapeutic resistance and tumor angiogenesis. Therefore, targeting cancer stem cells may improve patient survival. We interrogated the role of a neuronal cell adhesion molecule, L1CAM, in glioma stem cells as L1CAM regulates brain development and is expressed in gliomas. L1CAM(+) and CD133(+) cells cosegregated in gliomas, and levels of L1CAM were higher in CD133(+) glioma cells than normal neural progenitors. Targeting L1CAM using lentiviral-mediated short hairpin RNA (shRNA) interference in CD133(+) glioma cells potently disrupted neurosphere formation, induced apoptosis, and inhibited growth specifically in glioma stem cells. We identified a novel mechanism for L1CAM regulation of cell survival as L1CAM knockdown decreased expression of the basic helix-loop-helix transcription factor Olig2 and up-regulated the p21(WAF1/CIP1) tumor suppressor in CD133(+) glioma cells. To determine if targeting L1CAM was sufficient to reduce glioma stem cell tumor growth in vivo, we targeted L1CAM in glioma cells before injection into immunocompromised mice or directly in established tumors. In each glioma xenograft model, shRNA targeting of L1CAM expression in vivo suppressed tumor growth and increased the survival of tumor-bearing animals. Together, these data show that L1CAM is required for maintaining the growth and survival of CD133(+) glioma cells both in vitro and in vivo, and L1CAM may represent a cancer stem cell-specific therapeutic target for improving the treatment of malignant gliomas and other brain tumors.
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