Red fluorescent AIEgens based multifunctional nonviral gene vectors for the efficient combination of gene therapy and photodynamic therapy in anti-cancer.

Precise molecular engineering of AIEgens-based cationic delivery systems for high transfection efficiency (TE) and effective photodynamic therapy (PDT) holds a huge potential for cancer treatment. Herein, three amphiphiles (DT-C6/8/12-M) consisting of di(triazole-[12]aneN3) (M) and 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenyl-ethylene (DT) units have been developed to achieve luminescent tracking, efficient TE, and effective PDT in vitro and in vivo. These compounds exhibited strong aggregated induced emission (AIE) at 630 nm and mega Stokes shifts of up to 160 nm. They were able to bind DNA into nanoparticles with suitable sizes, positive surface potential, and good biocompatibility in the presence of DOPE. Among them, vector DT-C12-M/DOPE with n-dodecyl linker achieved a transfection efficiency as high as 42.3 folds that of Lipo2000 in PC-3 cell lines. DT-C12-M/DOPE exhibited the capability of successful endo/lysosomal escape and rapid nuclear delivery of pDNA, and the gene delivery process was clearly monitored via confocal laser scanning microscopy. Moreover, efficient reactive oxygen species (ROS) generation by DT-C12-M upon light irradiation led to effective PDT in vitro . We further show that combination of p53 gene therapy and PDT dramatically enhanced cancer therapeutic outcome in vivo. This "three birds, one stone" strategy offers a novel and promising approach for real-time tracking of gene delivery and better cancer treatment.

Comparison of resting-state spontaneous brain activity between treatment-naive schizophrenia and obsessive-compulsive disorder.

BACKGROUND: Schizophrenia (SZ) and obsessive-compulsive disorder (OCD) share many demographic characteristics and severity of clinical symptoms, genetic risk factors, pathophysiological underpinnings, and brain structure and function. However, the differences in the spontaneous brain activity patterns between the two diseases remain unclear. Here this study aimed to compare the features of intrinsic brain activity in treatment-naive participants with SZ and OCD and to explore the relationship between spontaneous brain activity and the severity of symptoms. METHODS: In this study, 22 treatment-naive participants with SZ, 27 treatment-naive participants with OCD, and sixty healthy controls (HC) underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree of centrality (DC) were performed to examine the intrinsic brain activity of participants. Additionally, the relationships among spontaneous brain activity, the severity of symptoms, and the duration of illness were explored in SZ and OCD groups. RESULTS: Compared with SZ group and HC group, participants with OCD had significantly higher ALFF in the right angular gyrus and the left middle frontal gyrus/precentral gyrus and significantly lower ALFF in the left superior temporal gyrus/insula/rolandic operculum and the left postcentral gyrus, while there was no significant difference in ALFF between SZ group and HC group. Compared with HC group, lower ALFF in the right supramarginal gyrus/inferior parietal lobule and lower DC in the right lingual gyrus/calcarine fissure and surrounding cortex of the two patient groups, higher ReHo in OCD group and lower ReHo in SZ group in the right angular gyrus/middle occipital gyrus brain region were documented in the present study. DC in SZ group was significantly higher than that in HC group in the right inferior parietal lobule/angular gyrus, while there were no significant DC differences between OCD group and HC group. In addition, ALFF in the left postcentral gyrus were positively correlated with positive subscale score (r = 0.588, P = 0.013) and general psychopathology subscale score (r = 0.488, P = 0.047) respectively on the Positive and Negative Syndrome Scale (PANSS) in SZ group. ALFF in the left superior temporal gyrus/insula/rolandic operculum of participants with OCD were positively correlated with compulsion subscale score (r = 0.463, P = 0.030) on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The longer the illness duration in SZ group, the smaller the ALFF of the left superior temporal gyrus/insula/rolandic operculum (Rho = 0.-492, P = 0.020). The longer the illness duration in OCD group, the higher the ALFF of the right supramarginal gyrus/inferior parietal lobule (Rho = 0.392, P = 0.043) and the left postcentral gyrus (Rho = 0.385, P = 0.048), and the lower the DC of the right inferior parietal lobule/angular gyrus (Rho = - 0.518, P = 0.006). CONCLUSION: SZ and OCD show some similarities in spontaneous brain activity in parietal and occipital lobes, but exhibit different patterns of spontaneous brain activity in frontal, temporal, parietal, occipital, and insula brain regions, which might imply different underlying neurobiological mechanisms in the two diseases. Compared with OCD, SZ implicates more significant abnormalities in the functional connections among brain regions.

Lnc-UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9-Mediated CDK6 Down-regulation.

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc-UCID (lncRNA up-regulating CDK6 by interacting with DHX9). Lnc-UCID was up-regulated in hepatocellular carcinoma (HCC), and a higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain-of-function and loss-of function studies revealed that lnc-UCID enhanced cyclin-dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc-UCID-silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc-UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850-1030-nt domain of lnc-UCID interacted physically with DEAH (Asp-Glu-Ala-His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post-transcriptionally suppressed CDK6 expression by binding to the 3'-untranslated region (3'UTR) of CDK6 mRNA. Further investigation disclosed that lnc-UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6-3'UTR. In an attempt to explore the mechanisms responsible for lnc-UCID up-regulation in HCC, we found that the lnc-UCID gene was frequently amplified in HCC. Furthermore, miR-148a, whose down-regulation was associated with an increase of lnc-UCID in HCC, could bind lnc-UCID and inhibit its expression. Conclusion: Up-regulation of lnc-UCID, which may result from amplification of its gene locus and down-regulation of miR-148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.

[Research on the method of interference correction for nondispersive infrared multi-component gas analysis].

A method of interference correction for nondispersive infrared multi-component gas analysis was described. According to the successive integral gas absorption models and methods, the influence of temperature and air pressure on the integral line strengths and linetype was considered, and based on Lorentz detuning linetypes, the absorption cross sections and response coefficients of H2O, CO2, CO, and NO on each filter channel were obtained. The four dimension linear regression equations for interference correction were established by response coefficients, the absorption cross interference was corrected by solving the multi-dimensional linear regression equations, and after interference correction, the pure absorbance signal on each filter channel was only controlled by the corresponding target gas concentration. When the sample cell was filled with gas mixture with a certain concentration proportion of CO, NO and CO2, the pure absorbance after interference correction was used for concentration inversion, the inversion concentration error for CO2 is 2.0%, the inversion concentration error for CO is 1.6%, and the inversion concentration error for NO is 1.7%. Both the theory and experiment prove that the interference correction method proposed for NDIR multi-component gas analysis is feasible.