Effect of glycogen synthase kinase 3β on treatment of corticosterone-induced depression in mice treated with Xiaobuxintang-2

Objective:Xiaobuxintang-2(XBXT-2)has antidepressant effects,but the underlying mechanism is still unclear.In this study,we used the corticosterone-induced depression mouse model to study the antidepressant effect of XBXT-2and its underlying mechanisms.Methods:A mouse model of depression was induced by corticosterone.The mice were divided into 5 groups:(i)control group,(ii)corticosterone group(CORT),(iii)corticosterone+XBXT-2(CORT+XBXT-2)group,(iv)corticosterone+XBXT-2+lentiviral empty group(CORT+XBXT-2+no-load),(v)corticosterone+XBXT-2+lentivirus GSK3βOverexpression group(CORT+XBXT-2+GSK3β).The expression level of GSK3βin the hippocampus was detected by immunoblotting,and the depression status of the mice was evaluated by forced swimming test and tail suspension test.Results:The GSK3βlentivirus induced the high expression of GSK3βin the hippocampus of mice,and the mRNA and protein levels were significantly increased compared with the control group.The immobility time is significantly increased in corticosterone injection-induced depression model mice(CORT group),and XBXT-2 can effectively reduce the immobility time of depression model mice.Overexpression of GFP empty lentivirus did not affect mouse behavior,whereas overexpression of GSK3βsignificantly increased immobility time in depression model mice according to forced swimming and tail suspension experiments.Conclusion:High expression of GSK3βin the hippocampus of mice can inhibit the therapeutic effect of XBXT-2 on the corticosterone-induced depression in mice.

Features and therapeutic potential of T-cell receptors in high-grade glioma

Background: Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value. Methods: During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data. Results: The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t =-5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t =-2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence. Conclusions: HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

ARAP++:an extension of the local/global approach to mesh parameterization

Mesh parameterization is one of the fundamental operations in computer graphics(CG) and computeraided design(CAD). In this paper, we propose a novel local/global parameterization approach, ARAP++, for singleand multi-boundary triangular meshes. It is an extension of the as-rigid-as-possible(ARAP) approach, which stitches together 1-ring patches instead of individual triangles. To optimize the spring energy, we introduce a linear iterative scheme which employs convex combination weights and a fitting Jacobian matrix corresponding to a prescribed family of transformations. Our algorithm is simple, efficient, and robust. The geometric properties(angle and area)of the original model can also be preserved by appropriately prescribing the singular values of the fitting matrix. To reduce the area and stretch distortions for high-curvature models, a stretch operator is introduced. Numerical results demonstrate that ARAP++ outperforms several state-of-the-art methods in terms of controlling the distortions of angle, area, and stretch. Furthermore, it achieves a better visualization performance for several applications, such as texture mapping and surface remeshing.