Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide1, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified 2, despite analysis of more than 9,000 cases3. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

SummaryAdversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

The expression of microRNA-125b (miR-125b) has been investigated in many human cancers. It has been demonstrated to be downregulated in certain types of cancer, such as bladder cancer, thyroid anaplastic carcinomas, squamous cell carcinoma of the tongue, hepatocellular carcinoma, ovarian and breast cancer. In the present study, we examined the effects of miR-125b on bladder cancer cell migration and invasion. Following transfection of miR-125b, the expression of miR-125b was analyzed in T24 and EJ bladder cancer cells. Additionally, cell migration, cell invasion and luciferase assays, as well as western blot analysis were conducted in the bladder cancer cells. In this study, we demonstrated that miR-125b inhibited cell migration and invasion in T24 and EJ cells. We also provided the first evidence that miR-125b may directly target matrix metalloproteinase 13 (MMP13) in bladder cancer. Our study provided evidence that miR-125b suppresses cell migration and invasion by targeting MMP13 in bladder cancer cell lines. These results suggested that miR-125b could be used for the development of new molecular markers and therapeutic approaches to inhibit bladder cancer metastasis.

Abstract. has been previously reported to be downregulated in specific types of cancer, including colorectal, bladder, oral squamous cell, pituitary, cervical, nasopharyngeal, lymphoma and prostate cancer. In the present study, the effects of miR-143 on prostate cancer cell migration and invasion were examined. Following transfection with miR-143, miR-143 expression, cell migration and invasion assays, luciferase assay and western blot analysis were conducted in prostate cancer cell lines. The results indicated that miR-143 inhibits cell migration and invasion in DU145 and PC-3 cells. In addition, to the best of our knowledge, miR-143 was reported for the first time to directly target matrix metalloproteinase 13 (MMP-13) in prostate cancer. The results of the present study demonstrated that miR-143 suppresses cell migration and invasion by targeting MMP-13 in prostate cancer cell lines. These results indicated that miR-143 may be suitable for the development of novel molecular markers and therapeutic approaches to inhibit metastasis in prostate cancer.

microRNA‑145 (miR‑145) has been reported to be frequently downregulated in various types of cancer, including renal, prostate, bladder, lung and colon cancer, as well as B‑cell malignancies. The present study examined the effects of miR‑145 on the cell proliferation, migration and invasion of renal cell carcinoma (RCC). Following transfection of miR‑145, an MTT, cell migration, cell invasion and luciferase assays, and western blot analysis were conducted in RCC cell lines. The present study demonstrated that miR‑145 inhibited cell proliferation, migration and invasion in 786‑O and A498 cells. The present study also demonstrated for the first time, to the best of our knowledge, that miR‑145 may directly target matrix metallopeptidase‑11 (MMP‑11) in RCC. miR‑145 was demonstrated to suppress cell proliferation, migration and invasion by targeting MMP‑11 in RCC cell lines. These results suggested that it may be investigated as a predictive marker for the early detection of tumor metastasis and for targeting therapeutic drugs to inhibit the invasion of RCC.

Ginseng (Panax ginseng) is a perennial herbaceous plant belonging to Panax genus of Araliaceae. Ginsenosides are a kind of important compounds in ginseng and minor ginsenosides are secondary metabolic derivatives of ginsenosides. Studies have shown that minor ginsenosides have many pharmacological effects, such as antioxidant, anti-tumor, anti-platelet aggregation, and neuroprotective effects. However, the therapeutic effects of minor ginsenosides are limited due to poor solubility in water, short half-life, and poor targeting accuracy. In recent years, to improve the application efficiency, the research on the nanocrystallization of minor ginsenosides have attracted extensive attention from researchers. This review focuses on the classification, preparation methods, pharmacological effects, and action mechanisms of minor ginsenoside nanoparticles, as well as existing problems and future direction of relevant research, which provides a reference for the in-depth research of minor ginsenoside nanoparticles.

We show that stable bright solitons can appear in a medium with spatially inhomogeneous self-defocusing (SDF) nonlinearity of a double-well structure. For a specific choice of the nonlinearity parameters, we obtain exact analytical solutions for the fundamental bright solitons. By making use of the linear stability analysis, the stability region in the parameter space for the exact fundamental bright soliton is obtained numerically. We also show the bifurcation from an antisymmetric to an asymmetric bright soliton for the SDF double-well nonlinearity.

We investigate a four-parameter class of quasi-exactly solvable double-well potentials. We present an analytical solution for this class of double-well potentials in terms of the confluent Heun functions. It is shown that under specific values of the potential parameters, certain eigenenergies and eigenfunctions can be found exactly in an explicit form. In addition, these exact analytical solutions are used to construct exact localized solutions for the nonlinear Schrödinger equation with a double-well self-defocusing nonlinearity.