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Lung cancer is one of the most prevalent and malignant cancers, among which lung adenocarcinoma (LUAD) accounts for the majority and remains a major cause of cancer-related mortality worldwide (Cui et al., 2019). Despite the growing intensity of research on the pathobiology and progression of lung cancer and the fact that many genes have been identified as potential drivers and targets for therapy (Luo et al., 2019; Zhang et al., 2019), the treatment and prognosis of lung cancer patients have hardly improved. Therefore, this study aimed to investigate the precise mechanism of lung cancer development and explore efficient diagnostic and therapeutic methods for clinical treatment.

Background Hepatocellular carcinoma (HCC) is one of the most aggressive cancers. The present study aimed to investigate the effects of GRHPR on the proliferation and metastasis of HCC and to identify the miRNA targeting GRHPR to understand the underlying mechanism of miR-138-5p/GRHPR on HCC proliferation and metastasis. Methods The expression levels of GRHPR and miR-138-5p were detected in HCC tissues and cells. Bioinformatic analysis and dual-luciferase reporter assay were carried out to confirm that GRHPR was a target gene of miR-138-5p. HCC cell lines overexpressing GRHPR were established to detect the roles of GRHPR in HCC cell proliferation, migration and invasion. The biological function of miR-138-5p targeting to GRHPR in HCC cell lines was also evaluated. The xenograft mouse model was established to investigate the functions of GRHPR in vivo. Results GRHPR was markedly downregulated in human HCC samples, whereas miR-138-5p was upregulated in HCC samples. The expression of GRHPR was regulated by miR-138-5p in HCC cell lines. HCC cell proliferation, migration and invasion could be suppressed by GRHPR overexpression and GRHPR exerted an anti-tumor effect in a xenograft mouse model. However, the inhibition of GRHPR by miR-138-5p promoted the proliferation and invasive properties of HCC cells. MiR-138-5p could regulate the phosphorylation levels of PI3K and AKT related to the phosphatidylinositol signaling pathway via inhibiting GRHPR expression. Conclusions This study suggests that GRHPR may play a significant role in HCC and its function is regulated by miR-138-5p.

Background In 2011, California enacted its public safety realignment initiative (realignment) motivated by a U.S. Supreme Court ruling to reduce state prison overcrowding and in effort to reduce recidivism. Realignment transferred authority for lower-level felony offenders from the state to the counties, leading to a rapid reduction in state prison incarceration levels. Objective This study drew on a unique dataset to assess the effects of California’s efforts to downsize the prison system on maternal incarceration levels and to better understand the characteristics of incarcerated mothers and their children. Methods Incarceration records concerning all women in California state prisons between 2010 and 2012 (N = 16,917) were linked to 7.5 million vital birth records dating to 1999 to identify incarcerated women who had given birth. Multinomial logistic regression models were specified to better understand offense type differences among incarcerated mothers versus nonmothers. Results Findings indicate that realignment disproportionately affected women. The number of men entering prison decreased 67.8% between 2010 and 2012. In comparison, the number of women entering prison decreased 78.5%. Further, more than half of incarcerated women had given birth. Mothers were more likely than nonmothers to be convicted of nonviolent crimes. Discussion This study underscores how prison downsizing can disproportionately reduce incarceration levels for women. Given that such large proportion of incarcerated women were mothers, this policy change may have potential spillover next-generation benefits. Finally, this work reinforces the potential to use linked administrative records to study incarcerated populations.

BCAT1 is up-regulated and acts as an oncogenic factor in many types of cancers, but its role in lung adenocarcinoma (LUAD) development is not clearly understood. Here we found BCAT1 protein level was up-regulated in tumor tissues, which was positively associated with TNM stage and local lymph node metastasis of LUAD patients. BCAT1 knockdown inhibited cell growth and mobility while BCAT1 overexpression promoted LUAD development both in vitro and in vivo. BCAAs metabolism and mitochondrial respiration were enhanced in BCAT1 overexpression cells, which were more sensitive to Leucine and Isoleucine supplements, compared to control cells. Moreover, RNA sequencing analysis suggested that differentially expressed genes (DEGs) in BCAT1 overexpression LUAD cells were enriched in metabolism, signal transduction, and immune response processes, and BCAT1 overexpression decreased NFKBIB mRNA level that induced NF-κB pathway activation in LUAD cells. As an inhibitor of NF-κB pathway, ammonium pyrrolidinedithiocarbamate (PDTC) treatment predominately counteracted the effect of NF-κB pathway activation and inhibited LUAD cells proliferation and migration, especially cells with BCAT1 overexpression. Taken together, our findings point a key role for BCAT1 in promoting LUAD development through metabolic reprogramming and NF-κB pathway activation, which provides promising molecular biomarker and therapeutic targets for LUAD diagnosis and treatment.

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed types of cancer in the world. Post-translational modifications, such as phosphorylation, serve an essential role during cancer development. To identify aberrant phosphorylation in HCC, a multiplexed tandem mass tag approach combined with liquid chromatography tandem-mass spectrometry was used in the present study. The results are available via ProteomeXchange (identifier no. PXD013934). A total of 4,780 phosphorylated sites distributed on 2,209 proteins were identified and quantified, including 74 and 459 phosphorylated upregulated and downregulated proteins, respectively. Bioinformatic analysis revealed differences and similarities between HCC and normal tissues. Gene Ontology enrichment analysis provided information on biological processes, molecular functions, cellular components and sub-cellular localizations. Protein domains enrichment of differentially expressed proteins was analyzed using InterPro database. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed pathways that may potentially be involved in HCC. Integrative analysis of the functions, pathways, motifs of phosphorylated peptides, protein domains and protein interactions established a profile of the phosphoproteome of HCC, which may contribute to identify novel biomarkers for the diagnosis and prognosis of HCC, as well as novel therapeutic targets for HCC treatment.

This qualitative study applied a life course framework to characterize the nature of interpersonal partner relationships of Mexican American young adult men affiliated with street gangs during their adolescence. Data come from a 15-year longitudinal mixed-method cohort study conducted in San Antonio, Texas. We analyzed semi-structured interviews conducted with a subsample (n = 40) during the course of three face-to-face sessions to explore the men’s motivations, aspirations, and goals to lead conventional lives, despite their criminal justice involvement. Specifically, we focus on the complex nature of maintaining ties to children, the navigation of complicated family structures, the processes of seeking partners with economic resources, and on partnerships with criminal and delinquent partners. We document the complex interpersonal nature of these relationships as men contend with serial incarceration and their desires and motivations to desist from criminal behavior.

BACKGROUND: Homeless youth in the United States have high rates of substance use. Existing research has identified social network composition and street-associated stressors as contributing factors. Incarceration is a highly prevalent stressor for homeless youth. Its effect on youth’s social network composition and substance use, however, has been neglected. AIMS: This study investigated the direct and indirect associations between incarceration history and substance use (through social networks) among homeless youth in Los Angeles, California. METHODS: A sample of 1,047 homeless youths were recruited between 2011 and 2013. Computerized self-administrated surveys and social network interviews were conducted to collect youth’s sociodemographic characteristics, incarceration history, social network composition, and substance use. Bootstrapping was used to identify the direct and indirect associations between youth’s incarceration history and substance use. RESULTS: Incarceration history was positively associated with youth’s cannabis, methamphetamine, and injection drug use. The percentage of cannabis-using peers partially mediated the associations between incarceration history and youth’s cannabis, cocaine, and heroin use. The percentage of methamphetamine-using peers partially mediated the associations between incarceration history and youth’s methamphetamine, cocaine, and injection drug use. The percentage of heroin-using peers partially mediated the association between incarceration history and youth’s heroin use. Moreover, the percentage of peers who inject drugs partially mediated the associations between incarceration history and youth’s methamphetamine, heroin, and injection drug use. DISCUSSION: Incarceration history should be taken to a more central place in future research and practice with homeless youth in the United States.

To deal with problems such as ill-structured conventional transit network and low operational efficiency, this paper presents a method to use transit scheduling value and passenger transit travel time as an optimal objective function to build an optimization model, as an effort to optimize conventional transit network. It aims to improve traditional genetic algorithm, which combines the simulated annealing algorithm with the elitist strategy, and adopts the Python programming to solve the optimization model. The results show that the optimization model can output an optimal transit network and an appropriate scheduling scheme, proving that it is reasonable and feasible to use the improved genetic algorithm in the optimization of transit network.

Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

Introduction Tobacco advertising is widespread in urban areas with racial/ethnic minority and low-income households that participate in nutrition assistance programs. Tobacco sales and advertising are linked to smoking behavior, which may complicate matters for low-income families struggling with disparate health risks relating to nutrition and chronic disease. We investigated the relationship between the amount and type of tobacco advertisements on tobacco outlets and the outlet type and location. Methods By using field visits and online images, we inspected all licensed tobacco retail outlets in Philadelphia (N = 4,639). Point pattern analyses were used to identify significant clustering of tobacco outlets and outlets with exterior tobacco advertisements. Logistic regression was used to analyze the relationship between the outlet's acceptance of Supplemental Nutrition Assistance Program (SNAP) and Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and the presence of tobacco advertisements. Results Tobacco outlets with exterior tobacco advertisements were significantly clustered in several high-poverty areas. Controlling for racial/ethnic and income composition and land use, SNAP and WIC vendors were significantly more likely to have exterior (SNAP odds ratio [OR], 2.11; WIC OR, 1.59) and interior (SNAP OR, 3.43; WIC OR, 1.69) tobacco advertisements than other types of tobacco outlets. Conclusion Tobacco advertising is widespread at retail outlets, particularly in low-income and racial/ethnic minority neighborhoods. Policy makers may be able to mitigate the effects of this disparate exposure through tobacco retail licensing, local sign control rules, and SNAP and WIC authorization.

Background.White adipose tissue browning may be a promising strategy to combat obesity. UCP1 is strongly induced in White adipose tissue withβ3-adrenergic agonist treatment, but the causes of this increase have not been fully elucidated. This study aims to explore more miRNAs involved in the process of browning of visceral adipose tissue.Methods.Total of fourteen mice were randomly divided into control and study group. Study group mice were injected intraperitoneally with CL316243 once daily for seven days; meanwhile the control group were treated with 0.9% NaCl. After a 7-day period, the expression of genes involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues was analyzed by qPCR.Results.qPCR analysis revealed that UCP1, DIO2, CIDEA, and CPT1B in epididymal adipose tissue were overexpressed in CL316243 group. Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose tissue were significantly decreased in CL316243 group.Conclusion.This suggests that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the browning of epididymal adipose tissue by regulating UCP1 gene expression. In this study, we demonstrated that this increase of UCP1 is due, at least in part, to the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose tissue compared to control.

Autophagy plays an important role in the central nervous system. However, it is unknown how autophagy regulates cortical neurogenesis during early brain development. Here, we report that autophagy-related gene 5 (Atg5) expression increased with cortical development and differentiation. The suppression of Atg5 expression by knockdown led to inhibited differentiation and increased proliferation of cortical neural progenitor cells (NPCs). Additionally, Atg5 suppression impaired cortical neuronal cell morphology. We lastly observed that Atg5 was involved in the regulation of the β-Catenin signaling pathway. The β-Catenin phosphorylation level decreased when Atg5 was blocked. Atg5 cooperated with β-Catenin to modulate cortical NPCs differentiation and proliferation. Our results revealed that Atg5 has a crucial role in cortical neurogenesis during early embryonic brain development, which may contribute to the understanding of neurodevelopmental disorders caused by autophagy dysregulation.