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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.

Research on the role of incarceration history on the mental health of imprisoned mothers reveals contradictory findings. These inconsistencies are potentially attributable to the different incarceration histories across samples masked by the use of a dichotomized incarceration history measure. This study used incarceration trajectories over the life course to determine the nature and array of incarceration experiences detrimental to mental health. Using the Survey of Inmates in State and Federal Correctional Facilities dataset (N = 881), we conducted logistic regressions to examine the associations between imprisoned mothers’ incarceration trajectories and mental health problems. Findings suggested that incarceration trajectories were significantly associated with a post-traumatic stress disorder diagnosis and demonstrated a trend towards significance to be associated with anger symptoms and suicidal ideation. However, they were not significantly related to other mental health problems, such as depressive disorder and anxiety disorder. We concluded that mental health interventions need to be customized to the unique challenges encountered by subgroups of mothers with different incarceration experiences.

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.

Knowledge about the motivations for crack cocaine use and the long-term effects among people who inject heroin is limited. This study aims to understand motivations associated with this co-use drug...

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. To gain more insights into the transcriptomic landscape and molecular mechanism of HCC, we performed TMT-labelled tandem mass spectrometry (n = 4) and whole-transcriptome sequencing (n = 3) based on HCC tumour (T) and adjacent normal (N) tissues from seven HCC patients. To comprehensively evaluate the gene-regulatory circuits in HCC, differential expression and enrichment analyses were performed on the differentially expressed proteins (DEPs), genes (DEGs), miRNAs (555), lncRNAs (29) and circRNAs (895). A total of 977 proteins and 243 genes were found to be differentially expressed in HCC tumours compared with adjacent normal tissues. HCC data from The Cancer Genome Atlas were used to validate the results. Combined with the results above, 56 DEP-DEGs with common changes in relative quantity were identified. Functional pathway analysis showed that the DEP-DEGs were mainly enriched in the spliceosome and various metabolic processes. Bioinformatics analysis showed that hsa-miR-1266-5p, hsa-miR-128-1-5p, hsa-miR-139-5p, hsa-miR-34b-3p and hsa-miR-570-3p were involved in the regulation of the hub genes mentioned above. The crucial coexpression (lncRNA-mRNA, circRNA-mRNA) and competing endogenous RNA interaction axes showed the possible functions of the lncRNAs and circRNAs. We explored potential cancer biomarkers by combining proteomic and transcriptomic studies. Our study provides a valuable resource for understanding regulatory mechanisms at the RNA level and may ultimately further assist in the development of diagnostic and/or therapeutic targets for HCC.

Although victim wrongs often contribute to assault and battery cases, the judicial examination and determination of victim wrongs in criminal trials in mainland China remain understudied. This is problematic because a thorough understanding of crime requires examining all parties involved to restore the truth. This study explored the examination and determination of victim wrongs in cases of assault and battery and identified reasons for the current trial practice in mainland China. We analyzed 447 criminal judgments of assault and battery cases in Jinan City in 2018 and conducted semistructured interviews with 27 judges in Shandong Province. Although victim wrongs prevailed among assault and battery cases, findings suggest that they were inadequately assessed and underrepresented in criminal judgments. Explanatory factors of this phenomenon include the judicial tradition of focusing on the accused, the absence of substantive provisions in judging victim wrongs, and the lack of procedural guarantee in examining victim wrongs (i.e., proposal of victim wrongs, victim’s appearance in court, evidence rules, and victim role conflicts). Specific suggestions for trial ideology shift, legislation change, and trial procedure reform under the quasi-inquisitorial system in mainland China were discussed.

Despite growing research on women’s offending trajectories, knowledge on the imprisonment experiences of women who are mothers is limited. This study used a nationally representative dataset of state and federal prisoners to identify and characterize subgroups of mothers based on incarceration histories. Group-based trajectory modeling identified four groups with distinct incarceration trajectories: stable escalating group, moderate declining group, adolescence-peak group, and young-adulthood-peak group. Bivariate analyses then suggested that different incarceration trajectories were associated with adverse life experiences (i.e., foster care placement, sexual abuse experience) and confinement experiences (i.e., number of episodes of prison confinement). Discussed are the future research directions and implications for criminal justice policies and interventions targeting imprisoned mothers.

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.

Research on the impact of incarceration history on the depressive symptoms of released women has yielded conflicting findings, potentially due to the use of an oversimplified dichotomized measure of incarceration history that masks the significant heterogeneity in women’s incarceration history across different studies. This study used Add Health measures that reflect the timing, duration, and frequency of incarceration to examine its association with released women’s depressive symptoms. Chi-square and t tests were conducted to characterize released women (n = 626) in comparison to women without an incarceration history (n = 7237). Simple correlation analyses and multiple linear regression were then used to determine the association between incarceration history and released women’s depressive symptoms. Findings revealed that the timing, duration, and frequency of incarceration were not significant correlates of released women’s depressive symptoms. Instead, experiences of cumulative disadvantages were significant predictors. We concluded that the effects of cumulative disadvantages on released women’s depressive symptoms might outsize the impact of incarceration history.

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.

RNA is a key player in the cellular central dogma, including RNA transcription and protein synthesis. However, it is unknown whether RNA can directly interfere with DNA synthesis. Recently, we have found in vitro that while binding to DNA polymerase nonspecifically, RNA can transform DNA polymerase to display a moonlighting activity, dNTP phosphatase, in turn interfering with DNA synthesis. This phosphatase activity removes the γ-phosphate from dNTPs (generating dNDPs) and subsequently removes the β-phosphate from the formed dNDPs (generating dNMPs), confirmed by the noncleavable α,β-CH2-dGTP and β,γ-CH2-dGTP analogues. We also found that dGTP is the best substrate for the phosphatase, and the dNTP phosphatase activity is sensitive to the reaction medium. In addition, we have revealed that RNA can tune the activity of closely related proteins and give rise to new catalytic functions with subtle differences. Moreover, we have demonstrated in vitro that at the lower dNTP level, this phosphatase can directly...

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.

Non-Latinx black and Latinx youth have reported more frequent Internet use compared to White youth, yet problematic Internet use among these groups of youth remains underexplored. This study aimed to validate the Problematic Internet Use Questionnaire-Short Form (PIUQ-SF) and investigate the characteristics of problematic Internet use among non-Latinx black and Latinx youth. Cross-sectional data were collected from a convenience sample of 235 high school students in Southeastern Florida (Mean Age = 16.1; 69.2% non-Latinx black; 27.4% Latinx). Psychometric analyses supported the reliability and construct validity of the PIUQ-SF among non-Latinx black and Latinx youth. Latent profile analyses revealed that 37.2% of non-Latinx black youth and 25.4% of Latinx youth were identified as having problematic Internet use. Multivariate regression analyses revealed that less parental monitoring was linked to higher levels of problematic Internet use among non-Latinx black and Latinx youth. Further, sleep problems were positively related to problematic Internet use among non-Latinx black youth. The present findings provide insight into the problematic Internet use among these understudied minority groups in the literature and have important implications for research and practice with non-Latinx black and Latinx youth.

In mammals, white adipose tissue (WAT) store energy, whereas brown adipose tissue (BAT) burns energy. As a thermogenic organ, BAT can help maintain body temperature during cold exposure. Owing to its important roles in energy metabolism and regulating triacylglycerol levels, BAT has received great attention in treating obesity and its related diseases. Recent studies have suggested that BAT may secrete factor(s)—batokines—to regulate whole-body energy metabolism. In this review, we summarize the recent advances in the formation and function of BAT, as well as molecules that regulate the activity of BAT and beige fat.

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.

This chapter examines how gender dynamics shape violent acts among Mexican American young adult males with a history of adolescent gang membership. We use the concept of hegemonic masculinity to examine the various ways that gender is performed in acts of violence (Connell, 1995). Masculinity is not a fixed entity or individual personality traits, masculinities are “configurations of practice that are accomplished in social action and, therefore, can differ according to the gender relations in a particular setting” (Connell & Messerschmidt, 2005:836). In other words, “gender identity is never a completed project, but always a developmental process which unfolds within a social context” (Messner, 1990:209). Nevertheless, the tendencies for aggression and violence are central to what it means to be masculine (Messerschmidt, 2000; Crowley, Foley et al., 2008) because “real men” must show others that they are not afraid (Kimmel, 2010). We examine the unfolding of masculine identity among disadvantaged Mexican American men in two different yet related contexts: violent acts with other men and the retelling of these violent acts. Among disadvantaged men, in general, social class is central to masculinity because these men are likely to have limited options in accomplishing their masculinity compared to men with more advantages (Britton, 2011; Messerschmidt, 1993; Stretesky & Pogrebin, 2007). The type of masculinity expressed by Mexican American males, more specifically, varies depending on a constellation of variables related to social class including income, generational status, education, and association with the criminal justice system (Rios, 2011; Valdez, 2007).

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.