Grace-AKO: a novel and stable knockoff filter for variable selection incorporating gene network structures

Motivation Variable selection is a common statistical approach to identifying genes associated with clinical outcomes of scientific interest. There are thousands of genes in genomic studies, while only a limited number of individual samples are available. Therefore, it is important to develop a method to identify genes associated with outcomes of interest that can control finite-sample false discovery rate (FDR) in high-dimensional data settings. Results This article proposes a novel method named Grace-AKO for graph-constrained estimation (Grace), which incorporates aggregation of multiple knockoffs (AKO) with the network-constrained penalty. Grace-AKO can control FDR in finite-sample settings and improve model stability simultaneously. Simulation studies show that Grace-AKO has better performance in finite-sample FDR control than the original Grace model. We apply Grace-AKO to the prostate cancer data in The Cancer Genome Atlas program by incorporating prostate-specific antigen (PSA) pathways in the Kyoto Encyclopedia of Genes and Genomes as the prior information. Grace-AKO finally identifies 47 candidate genes associated with PSA level, and more than 75% of the detected genes can be validated

Long Noncoding RNA EGFR-AS1 Promotes Cell Proliferation by Increasing EGFR mRNA Stability in Gastric Cancer

Background/Aims: LncRNA EGFR-AS1 is an antisense transcript of EGFR, which plays a key role in gastric cancer progression. This study was aimed to explore the effects of lncRNA EGFR-AS1 on GC and the underling mechanisms. Methods: The silencing of EGFR-AS1 expression was performed by using EGFR-AS1 shRNA lentivirus in MGC803 and SGC-7901 GC cell. The levels of lncRNA EGFR-AS1 and EGFR were detected by qPCR and western blot. Cell proliferation was assessed by CCK-8, EdU, and colony formation assays. The EGFR mRNA stability was explored by using RNA synthesis inhibitor α-amanitin. Results: In our study, EGFR-AS1 significantly up-regulated in GC tissues and correlated with tumor size. And the expression of EGFR-AS1 positively correlated with EGFR in tissues. Moreover, knock-down of EGFR-AS1 inhibited the proliferation of GC cells via suppressing EGFR-dependent PI3K/AKT pathway in vitro and in vivo. Mechanismly, depletion of EGFR-AS1 was found to decrease EGFR expression by reduction of EGFR mRNA stability. Conclusion: Our findings suggested that EGFR-AS1 might have an oncogenic effect on GC and serve as a potential target of GC

A tau fragment links depressive-like behaviors and cognitive declines in Alzheimer’s disease mouse models through attenuating mitochondrial function

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease

Understanding ambivalence of settlement: a qualitative study on time arrangement, gender relationship andidentity of rural-urban migrant families in Nanjing

published_or_final_versionSocial Work and Social AdministrationDoctoralDoctor of Philosoph

The sexuality of divorced mothers in Shanghai

abstractpublished_or_final_versionSocial Work and Social AdministrationMasterMaster of Philosoph

The sexuality of divorced mothers in Shanghai

abstractpublished_or_final_versionSocial Work and Social AdministrationMasterMaster of Philosoph

Repetitive Transcranial Magnetic Stimulation of the Brain Region Activated by Motor Imagery Involving a Paretic Wrist and Hand for Upper-Extremity Motor Improvement in Severe Stroke: A Preliminary Study

Approximately two-thirds of stroke survivors experience chronic upper-limb paresis; however, treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) can enhance motor function recovery in stroke survivors, but its efficacy is controversial. We compared the efficacy of stimulating different targets in 10 chronic stroke patients with severe upper-limb motor impairment. Motor imagery-based brain–computer interface training augmented with virtual reality was used to induce neural activity in the brain region during an imagery task. Participants were then randomly assigned to two groups: an experimental group (received high-frequency rTMS delivered to the brain region activated earlier) and a comparison group (received low-frequency rTMS delivered to the contralesional primary motor cortex). Behavioural metrics and diffusion tensor imaging were compared pre- and post rTMS. After the intervention, participants in both groups improved somewhat. This preliminary study indicates that in chronic stroke patients with severe upper-limb motor impairment, inducing activation in specific brain regions during motor imagery tasks and selecting these regions as a target is feasible. Further studies are needed to explore the efficacy of this intervention

Source apportionment of soil contamination based on multivariate receptor and robust geostatistics in a typical rural–urban area, Wuhan city, middle China

In this study topsoil samples were collected from 57 sites of Dongxihu District which is a typical Chinese urban–rural combination area, to analyze the causes and effects of 6 heavy elements. (Ni, Pb, As, Cu, Cd, and Hg) Pollution of Enrichment factor, multivariate statistics, geostatistics were adopted to study the spatial pollution pattern and to identify the priority pollutants and regions of concern and sources of studied metals. Most importantly, the study area was creatively divided into central urban, semi-urbanized, and rural areas in accordance with the characteristics of urban development and land use. The results show that the pollution degree of potential ecological risk assessment is Hg>Ni>Cu>As>Cd>Pb, and semi-urban regions> city center> rural areas. Results based on the proposed integrated source identification method indicated that As was probably sourced from agricultural sources (33.99%), Pb was associated with atmospheric deposition (50.11%), Cu was related to industrial source 1 (45.97%), Cd was mainly derived from industrial source 2 (42.97%) and Hg come mainly from industrial source 3 (56.22%). The pollution in semi-urban areas in urbanization need more attention