LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

Background/Aims: The long noncoding RNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been demonstrated to be a vital modulator in the proliferation and metastasis of ovarian cancer cells, but its potential molecular mechanism remains to be elucidated. In the current study, we aimed to uncover the biological role of lncRNA HOTAIR and its underlying regulatory mechanism in the progression and metastasis of ovarian cancer. Methods: HOTAIR expression was detected by quantitative RT-PCR (qRT-PCR) and northern blotting. The SKOV3 ovarian cancer cell line was chosen for the subsequent assays. In addition, the molecular mRNA and protein expression levels were examined by qRT-PCR and western blotting. The competitive endogenous RNA (ceRNA) mechanism was validated by bioinformatics analysis and a dual luciferase reporter gene assay. Results: HOTAIR expression was significantly higher in ovarian carcinoma tissues and cell lines than in the control counterparts. Both CCND1 and CCND2 were downstream targets of miR-206. The inhibition of HOTAIR elevated the expression of miR-206 and inhibited the expression of CCND1 and CCND2. Moreover, CCND1 and CCND2 were highly expressed in ovarian cancer tissues, and their expression was positively correlated with HOTAIR expression. Finally, the functional assays indicated that the anticancer effects of miR-206 could be rescued by the simultaneous overexpression of either CCND1 or CCND2 in ovarian cancer. Conclusion: HOTAIR enhanced CCND1 and CCND2 expression by negatively modulating miR-206 expression and stimulating the proliferation, cell cycle progression, migration and invasion of ovarian cancer cells

Charge Measurement of Cosmic Ray Nuclei with the Plastic Scintillator Detector of DAMPE

One of the main purposes of the DArk Matter Particle Explorer (DAMPE) is to measure the cosmic ray nuclei up to several tens of TeV or beyond, whose origin and propagation remains a hot topic in astrophysics. The Plastic Scintillator Detector (PSD) on top of DAMPE is designed to measure the charges of cosmic ray nuclei from H to Fe and serves as a veto detector for discriminating gamma-rays from charged particles. We propose in this paper a charge reconstruction procedure to optimize the PSD performance in charge measurement. Essentials of our approach, including track finding, alignment of PSD, light attenuation correction, quenching and equalization correction are described detailedly in this paper after a brief description of the structure and operational principle of the PSD. Our results show that the PSD works very well and almost all the elements in cosmic rays from H to Fe are clearly identified in the charge spectrum.Comment: 20 pages, 4 figure

Association of SLC11A1 Polymorphisms With Tuberculosis Susceptibility in the Chinese Han Population

Tuberculosis (TB) is an important health issue in the world. Although the relation of SLC11A1 polymorphisms with TB risk has been extensively studied, it has not been reported in the northwest Chinese Han population. Therefore, this study aimed to investigate the relationships between five polymorphisms in or near the SLC11A1 gene and susceptibility to TB. The Agena MassARRAY platform was conducted for genotyping from 510 TB patients and 508 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed through logistic regression adjustment age and gender to assess the relationships between polymorphisms and TB risk. Our results identified that rs7608307 was related to increased TB risk in males (CT vs. CC: OR = 1.69, 95%CI: 1.12–2.56, p = 0.013; CT-TT vs. CC: OR = 1.61, 95%CI: 1.08–2.41, p = 0.020) and age ≤41 group (CT vs. CC: OR = 1.66, 95%CI: 1.04–2.65, p = 0.035), respectively. The SNP rs13062 was associated with the TB risk both in males (p = 0.012) and age >41 group (p = 0.021). In addition, we observed that the CC genotype of rs4674301 was correlated with increased TB risk in females (p = 0.043). Our results demonstrated the relationships between polymorphisms (rs7608307, rs4674301, and rs13062) in or near the SLC11A1 gene and age- and sex-specific TB risk in the northwest Chinese Han population

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

Targeting long non-coding RNA DANCR inhibits triple negative breast cancer progression

Triple negative breast cancer (TNBC) is non-responsive to conventional anti-hormonal and Her2-targeted therapies, making it necessary to identify new molecular targets for therapy. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified participating in carcinogenesis of hepatocellular carcinoma, but its expression and potential role in TNBC progression is still unclear. In the present study, our results showed that DANCR expression was increased in TNBC tissues compared with the adjacent normal tissues using quantitative real-time PCR (qRT-PCR) in 63 TNBC specimens. Patients with higher DANCR expression correlated with worse TNM stages as well as a shorter overall survival (OS) using Kaplan–Meier analysis. When the endogenous DANCR was knocked-down via specific siRNA, cell proliferation and invasion were decreased obviously in the MDA-MB-231 cells. In vivo xenograft experiments showed that knockdown of the DANCR in MDA-MB-231 cells reduced the tumor growth significantly. Furthermore, a compendium of TNBC cancer stem cell markers such as CD44, ABCG2 transporter and aldehyde dehydrogenase (ALDH1) were greatly downregulated in the MDA-MB-231 cells with DANCR knockdown. Molecular mechanistic studies revealed that knockdown of DANCR was associated with increased binding of EZH2 on the promoters of CD44 and ABCG2, and concomitant reduction of expression of these genes suggested that they may be DANCR targets in TNBC. Thus, our study demonstrated that targeting DANCR expression might be a viable therapeutic approach to treat triple negative breast cancer

Depressive patient‐derived GABA interneurons reveal abnormal neural activity associated with HTR2C

Abstract Major depressive disorder with suicide behavior (sMDD) is a severe mood disorder, bringing tremendous burden to family and society. Although reduced gamma amino butyric acid (GABA) level has been observed in postmortem tissues of sMDD patients, the molecular mechanism by which GABA levels are altered remains elusive. In this study, we generated induced pluripotent stem cells (iPSC) from five sMDD patients and differentiated the iPSCs to GABAergic interneurons (GINs) and ventral forebrain organoids. sMDD GINs exhibited altered neuronal morphology and increased neural firing, as well as weakened calcium signaling propagation, compared with controls. Transcriptomic sequencing revealed that a decreased expression of serotoninergic receptor 2C (5‐HT2C) may cause the defected neuronal activity in sMDD. Furthermore, targeting 5‐HT2C receptor, using a small molecule agonist or genetic approach, restored neuronal activity deficits in sMDD GINs. Our findings provide a human cellular model for studying the molecular mechanisms and drug discoveries for sMDD

The development of laser powder bed fused nano-TiC/NiTi superelastic composites with hierarchically heterogeneous microstructure and considerable tensile recoverable strain

In this study, we fabricated the TiC nanoparticles decorated NiTi-based superelastic composites via laser powder bed fusion (LPBF) technology. Different from reactionlessness between TiC and NiTi in the conventional processes, high energy density of laser beam triggered strong diffusion behavior of carbon atoms from TiC nanoparticles and resulted in the precipitation of TiCx and attendant Ni-rich even Ti-rich intermetallics. Interestingly, these nanoprecipitates distributed along the intricate network of connected dislocations, architecting a novel submicron-scale cellular reinforcement structure and facilitating the formation of a hierarchically heterogeneous microstructure. The migration and distribution of TiC nanoparticles as well as the forming mechanism of the submicron cellular reinforcement structure were then elaborated. The study indicated laser scanning speed had significant influence on the distribution of TiC nanoparticles, the size of cellular structure and the matrix grain orientation. At the optimized parameter, the LPBF-fabricated nano-TiC/NiTi composites exhibited a weak orientation texture along the building direction, finer cellular structure and a considerable steady recoverable strain of 2.3% at a maximum tensile loading of 300 MPa