In the title compound, C(15)H(12)FN(3)O(3)·CH(3)OH, the dihedral angle between the quinazoline ring system and the benzene ring is 81.18 (9)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯N hydrogen bonds, generating [10-1] chains of alternating main mol-ecules and solvent mol-ecules. Weak C-H⋯O inter-actions are also observed.

The unfolded protein response (UPR) is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. However, tumor-specific UPR transducers are largely unknown. In the present study, we identified CD147, a cancer biomarker, as an UPR inducer in hepatocellular carcinoma (HCC). The expression of the major UPR target, Bip, was found to be positively associated with CD147 in human hepatoma tissues. By phosphorylating FAK and Src, CD147-enhanced TFII-I tyrosine phosphorylation at Tyr248. CD147 also induced p-TFII-I nuclear localization and binding to the Bip promoter where endoplasmic reticulum (ER) stress response element 1 (ERSE1)(-82/-50) is the most efficient target of the three ERSEs, thus increasing transcription of Bip. Furthermore, by inducing UPR, CD147 inhibited HCC cell apoptosis and decreased cell Adriamycin chemosensitivity, thus decreasing the survival rate of hepatoma-bearing nude mice. Together, these results reveal pivotal roles for CD147 in modulating the UPR in HCC and raise the possibility that CD147 is a target that promotes HCC cell apoptosis and increases the sensitivity of tumors to anti-cancer drugs. Therefore, CD147 inhibition provides an opportunity to enhance the efficacy of existing agents and represents a novel target for HCC treatment.Cell Death and Differentiation advance online publication, 18 May 2012; doi:10.1038/cdd.2012.60.

Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in myocardial dysfunction independent of other etiological factors. Abnormal intracellular calcium ([Ca(2+)](i)) homeostasis has been implicated in DCM and may precede clinical manifestation. Studies in cardiomyocytes have shown that diabetes results in impaired [Ca(2+)](i) homeostasis due to altered sarcoplasmic reticulum Ca(2+) ATPase (SERCA) and sodium-calcium exchanger (NCX) activity. Importantly, altered calcium homeostasis may also be involved in diabetes-associated endothelial dysfunction, including impaired endothelium-dependent relaxation and a diminished capacity to generate nitric oxide (NO), elevated cell adhesion molecules, and decreased angiogenic growth factors. However, the effect of diabetes on Ca(2+) regulatory mechanisms in cardiac endothelial cells (CECs) remains unknown. The objective of this study was to determine the effect of diabetes on [Ca(2+)](i) homeostasis in CECs in the rat model (streptozotocin-induced) of DCM. DCM-associated cardiac fibrosis was confirmed using picrosirius red staining of the myocardium. CECs isolated from the myocardium of diabetic and wild-type rats were loaded with Fura-2, and UTP-evoked [Ca(2+)](i) transients were compared under various combinations of SERCA, sarcoplasmic reticulum Ca(2+) ATPase (PMCA) and NCX inhibitors. Diabetes resulted in significant alterations in SERCA and NCX activities in CECs during [Ca(2+)](i) sequestration and efflux, respectively, while no difference in PMCA activity between diabetic and wild-type cells was observed. These results improve our understanding of how diabetes affects calcium regulation in CECs, and may contribute to the development of new therapies for DCM treatment.

The title compound, C(13)H(15)NO(2), was synthesized from 3,5-dimeth-oxy-benzaldehyde. The dihedral angle between the pyrrole and benzene rings is 89.91 (5)°. In the crystal, weak C-H⋯O and C-H⋯π interactions link the mol-ecules into a three-dimensional network.

Study Design. The expression of netrin-1 and its deleted in colorectal cancer (DCC) receptor were investigated in human lumbar discs using immunohistochemistry.Objective. To investigate the expression of netrin-1 and DCC receptor in human diseased and healthy lumbar intervertebral discs (IVDs) and to clarify the correlation between netrin-1 expression and the degree of neurovascular ingrowth.Summary of Background Data. Previous studies have showed neurovascular ingrowth into the inner regions of degenerated IVD, and suggested the ingrowth may contribute to discogenic low back pain. Netrin-1 is an axon guidance molecule which regulates axons seeking their final targets, and has been identified involved in a variety of pathological conditions, so is its DCC receptor. However, the role of netrin-1 in diseased IVDs remains unknown.Methods. Thirty-five diseased IVD specimens were collected from 34 patients with different lumbar diseases during posterior lumbar interbody fusion. 8 normal discs were obtained at autopsy as control. Using polyclonal or monoclonal antibody, the disc slides were immmunostained to detect the expression and distribution of netrin-1, the DCC, the neuronal marker(neurofilament), and the vascular endothelial cell marker(CD34).Results. Netrin-1 and DCC immunopositive cells distributed substantially from the annulus fibrosus (AF) to the nucleus pulposus (NP), and the immunopositivity was detected in the disc cells, endothelial cells and granulation tissue cells in the diseased discs. The percentage of netrin-1 positive disc cells of the NP was more than that of the AF. The expression of netrin-1 and DCC was weak in the normal discs. A significant positive correlation between the percentage of netrin-1 immunopositive disc cells and neurovascular scores was found.Conclusion. The increased expression of Netrin-1 and DCC in diseased IVDs compared with controls suggested they might play an important role in the process of neurovascular ingowth.

We explored a genetic detection method for Treponema pallidum (TP) in the peripheral blood of infected patients to compare the loads of treponemal DNA before and after therapy and to see if this new technique enabled assessment of therapeutic effect and detection of serum resistance. Polymerase chain reaction was used for a qualitative detection of TP DNA in peripheral blood and then a semiquantitative method was adopted to estimate the load of TP DNA in blood, both before and after treatment of syphilis. Among 30 untreated patients, three cases were TP DNA-positive. Among 42 treated patients with demonstrated serum resistance, three cases were TP DNA-positive. Five cases in which the rapid plasma reagin had become negative had no detectable TP DNA in their peripheral blood. The TP DNA load in blood after treatment was significantly lower than that before therapy. We conclude that the detection of TP DNA in peripheral blood of TP-infected patients is not yet sufficiently sensitive, but we observed that TP DNA load declines significantly after treatment.

Non-plane molecules with multiple large aromatic planes could be promising candidates to form various polyhedral micro/nano crystals through manipulating the different π…π stacking, tuning the cohesive energies of crystal facets, and controlling the kinetic growth process. Spirocyclic aromatic hydrocarbons (SAHs) have not only two cross-shaped aromatic planes but also offer the feature of supramolecular steric hindrance, making it favorable for the heterogeneous kinetic growth into highly symmetric polyhedra. Herein, we report that a novel SAH compound, spiro[fluorene-9,7'-dibenzo[c,h]acridine]-5'-one (SFDBAO), can self-assemble into various mono-dispersed shapes such as hexahedra, octahedra, and decahedra through the variation of either different types of surfactants, such as Pluronic 123 (P123) and cetyltrimethyl ammonium bromide (CTAB), or growth parameters. In addition, the possible mechanism of crystal facets growth has been proposed according to the SEM, XRD, TEM, and SAED characterization of organic polyhedral micro/nano-crystals. The unique cruciform-shaped SAHs have been demonstrated as fascinating supramolecular synthons for various highly symmetric polyhedral assembling.

Graphene, a single-atom-thick monolayer of sp2 carbon atoms perfectly arranged in a honeycomb lattice, is an emerging sensing material owing to its extraordinary properties, such as, exceptionally high specific surface area, electrical conductivity, and electrochemical potential window. In this study, we demonstrate that three-dimensional (3D), macroporous, highly conductive, and monolithic graphene foam synthesized by chemical vapor deposition represents a novel architecture for electrochemical electrodes. Being employed as an electrochemical sensor for detection of dopamine, 3D graphene electrode exhibits remarkable sensitivity (619.6 μA mM-1 cm-2) and lower detection limit (25 nM at a signal-to-noise ratio of 5.6), with linear response up to ~25 µM. And the oxidation peak of dopamine can be easily distinguished from that of uric acid - a common interferent to dopamine detection. We envision that the graphene foam provides a promising platform for the development of electrochemical sensors as well as other applications, such as, energy storage and conversion.

Few multi-city studies in Asian developing countries have examined the acute health effects of ambient nitrogen dioxide (NO(2)). In the China Air Pollution and Health Effects Study (CAPES), we investigated the short-term association between NO(2) and mortality in 17 Chinese cities. We applied two-stage Bayesian hierarchical models to obtain city-specific and national average estimates for NO(2). In each city, we used Poisson regression models incorporating natural spline smoothing functions to adjust for long-term and seasonal trend of mortality, as well as other time-varying covariates. We examined the associations by age, gender and education status. We combined the individual-city estimates of the concentration-response curves to get an overall NO(2)-mortality association in China. The averaged daily concentrations of NO(2) in the 17 Chinese cities ranged from 26μg/m(3) to 67μg/m(3). In the combined analysis, a 10-μg/m(3) increase in two-day moving averaged NO(2) was associated with a 1.63%[95% posterior interval (PI), 1.09 to 2.17], 1.80%(95% PI, 1.00 to 2.59) and 2.52%(95% PI, 1.44 to 3.59) increase of total, cardiovascular, and respiratory mortality, respectively. These associations remained significant after adjustment for ambient particles or sulfur dioxide (SO(2)). Older people appeared to be more vulnerable to NO(2) exposure. The combined concentration-response curves indicated a linear association. Conclusively, this largest epidemiologic study of NO(2) in Asian developing countries to date suggests that short-term exposure to NO(2) is associated with increased mortality risk.

Animals attain information about their environment through different sense organs. For example, the dominant external resource about the environment for rodents is obtained through olfaction. However, many environmental conditions (stress or enriched environment) are known to affect an animal's susceptibility to drug addiction. However, it is not known how external information is integrated and paired with drug stimuli to develop into addictive behavior. Here, we investigated the effects of olfactory epithelium lesions induced with ZnSO4 effusion (ZnE) on morphine-induced sensitization and conditioned place preference in mice. We found that the lesion of the olfactory epithelium attenuated the repeated morphine (40mg/kg)-induced behavioral sensitization and morphine-induced conditioned place preference (CPP) behaviors, such as hyper-locomotion during morphine (40mg/kg) conditioned training. Additionally, the expression of FosB-like proteins, transcription factors associated with behavioral alterations, in the nucleus accumbens of the brain was attenuated in morphine administered mice treated by ZnE. Taken together, these results indicated that lesion of the olfactory epithelium lead to a decrease in morphine sensitization and CPP behavior in mice as well as modulate specific molecular markers of neuroadaption to drugs of abuse. These findings also suggest that olfaction plays an important role in the development of addictive behaviors that can be modulated by external actions.