Cumulative ecological risk and nonsuicidal self-injury in adolescents: The mediation of depression and the moderation of impulsiveness.

BACKGROUND: This study is based on the biosocial model of nonsuicidal self-injury (NSSI), to explore the effects of cumulative ecological risk on adolescents' NSSI, the mediating effect of depression between cumulative ecological risk and adolescents' NSSI, and the moderating role of impulsiveness in this mediating pathway. METHODS: A total of 16 508 adolescents, with 7903 males (47.9%), participated in the study and completed the Cumulative Ecological Risk Questionnaire, the Short Form of the Center for Epidemiological Studies Depression Scale, the Impulsiveness assessment, and the Nonsuicidal Self-Injury Scale. RESULTS: (1) There was a significant positive correlation between cumulative ecological risk, depression, impulsiveness, and NSSI; (2) cumulative ecological risk significantly predicted adolescents' NSSI; (3) depression had a mediating effect between cumulative ecological risk and adolescents' NSSI; and (4) impulsiveness moderated both the effects of cumulative ecological risk on adolescents' depression and NSSI and the effects of depression on NSSI in adolescents. CONCLUSIONS: Impulsiveness and depression are risk factors for adolescent NSSI and play a crucial role between cumulative ecological risk and NSSI in adolescents.

Metabolic Profiling of Urinary Chiral Amino-Containing Biomarkers for Gastric Cancer Using a Sensitive Chiral Chlorine-Labeled Probe by HPLC-MS/MS.

Screening of characteristic biomarkers from chiral amino-containing metabolites in biological samples is difficult and important for the noninvasive diagnosis of gastric cancer (GC). Here, an enantiomeric pair of chlorine-labeled probes d-BPCl and l-BPCl was synthesized to selectively label d- and l-amino-containing metabolites in biological samples, respectively. Incorrect structural annotations were excluded according to the characteristic 3:1 abundance ratio of natural chlorine isotopes (35Cl and 37Cl) derived from the probes. A sensitive C18 HPLC-QQQ-MS/MS method in combination with the probes was then developed and applied in metabolomic analysis of amino-containing metabolites in urine samples. A total of 161 amino-containing metabolites were rapidly separated and determined, and 28 chiral amino acids and achiral glycine were quantified with good precision and accuracy. A total of 18 differential variables were discriminated by analyzing chiral amino-containing metabolites in urine samples of the GC patient and healthy person using the probe-based HPLC-MS/MS-MRM method combined with the orthogonal partial least squares discriminant analysis and Mann-Whitney U test with false discovery rate correction for multiple hypotheses. A diagnostic regression model including d-isoleucine, d-serine, and ß-(pyrazol-1-yl)-l-alanine and age was then constructed with an average prediction correctness of 88.9% in the validation set. This work established a close connection between gastric cancer and chiral amino-containing metabolites. The mass spectrometry data analyzed in the study are publicly available via Mendeley Data (DOI: 10.17632/4bd93j9yrr.1).

HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine.

N6-methyl-2'-deoxyadenosine (m6dA) is a newly discovered DNA epigenetic mark in mammals. N6-methyladenosine (m6A), 2'-O-methyladenosine (Am), N6,2'-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are common RNA modifications. Previous studies illustrated the associations between the aberrations of these methylated adenosines in nucleic acids and cancer. Herein, we developed Fe3O4/graphene-based magnetic dispersive solid-phase extraction for the enrichment and hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS/MS) for the measurements of m6dA, m6A, Am, m6Am, and m62A in human urine samples. We found that malic acid could improve the HILIC-based separation of these modified nucleosides and markedly enhance the sensitivity of their MS detection. With this method, we accurately quantified the contents of these modified adenine nucleosides in urine samples collected from gastric and colorectal cancer patients as well as healthy controls. We found that, relative to healthy controls, urinary m6dA and Am levels are significantly lower for gastric and colorectal cancer patients; while gastric cancer patients also exhibited lower levels of urinary m6A, the trend was opposite for colorectal cancer patients. Together, we developed a robust analytical method for simultaneous measurements of five methylated adenine nucleosides in human urine, and our results revealed an association between the levels of urinary methylated adenine nucleosides and the occurrence of gastric as well as colorectal cancers, suggesting the potential applications of these modified nucleosides as biomarkers for the early detection of these cancers.

Mediating effects of working memory on the relationship between chronic pain and overgeneral autobiographical memory.

This study is to explore the function of working memory (WM) and autobiographical memory (AM) in patients with chronic pain. Totally, 331 patients with chronic pain and 333 healthy controls were recruited. These subjects were subjected to assessment with Pain Assessment Protocol (PAP), Visual Analogue Scale (VAS), Working Memory Index (WMI) and Autobiographical Memory Test (AMT). Patients with chronic pain scored significantly lower in WMI and higher in overgeneral autobiographical memory (OGM) of AMT. Chronic pain was significantly negatively related with WM and positively related with OGM. The structural equation model indicated that WM mediated the relationship of chronic pain and OGM. These findings suggest that WM and AM are impaired in the patients with chronic pain,,chronic pain is closely related with OGM, and WM acts an important mediating role between chronic pain and OGM.

Overgeneral autobiographical memory in patients with chronic pain.

OBJECTIVE: Overgenerality and delay of the retrieval of autobiographical memory (AM) are well documented in a range of clinical conditions, particularly in patients with emotional disorder. The present study extended the investigation to chronic pain, attempting to identify whether the retrieval of AM in patients with chronic pain tends to be overgeneral or delayed. DESIGN: With an observational cross-sectional design, we evaluated the AM both in patients with chronic pain and healthy controls by Autobiographical Memory Test. Pain conditions were assessed using the pain diagnostic protocol, the short-form McGill Pain Questionnaire (SF-MPQ), and the Pain Self-Efficacy Questionnaire (PSEQ). Emotion was assessed using the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory. SUBJECTS AND SETTINGS: Subjects included 176 outpatients with chronic pain lasting for at least 6 months and 170 healthy controls. RESULTS: 1) Compared with the healthy group, the chronic pain group had more overgeneral memories (OGMs) (F = 29.061, P < 0.01) and longer latency (F = 13.602, P < 0.01). 2) In the chronic pain group, the stepwise multiple regression models for variables predicting OGM were significant (P < 0.01). Specifically, the variance in OGM scores could be predicted by the BDI score (9.7%), pain chronicity (4.3%), PSEQ score (7.1%), and Affective Index (of SF-MPQ) score (2.7%). 3) In the chronic pain group, the stepwise multiple regression models for variables predicting latency were significant (P < 0.05). Specifically, the variance in latency could be predicted by age (3.1%), pain chronicity (2.7%), pain duration (4.3%), and PSEQ score (2.0%). CONCLUSIONS: The retrieval of AM in patients with chronic pain tends to be overgeneral and delayed, and the retrieval style of AM may be contributed to negative emotions and chronic pain conditions.

Memory impairment in chronic pain patients and the related neuropsychological mechanisms: a review.

OBJECTIVE: This study provides a comprehensive review of the literature on memory impairment and the potential effective factors in patients with chronic pain. METHODS: A literature search of databases PubMed, EMBASE, SpringerLink, and PsycINFO until September 2012 was conducted using the keywords 'memory' and 'chronic pain'. The study emphasises on publications over the past 20 years. RESULTS: Memory impairment in chronic pain patients is substantial, but the aspects of memory (e.g. working memory, long-term memory, and autobiographical memory) in chronic pain patients and the potentially related factors (e.g. age, level of education, pain conditions, emotion, neural network, and use of analgesics) are modest. Memory impairment is interpreted with the attention-narrowing hypothesis and the capacity-reduction hypothesis. CONCLUSIONS: The currently available data and theory have explained memory impairment in chronic pain patients, but many controversies remain. Future research should focus on the subclinical characteristics of chronic pain, enlarging the sample size, and emphasise on the experimental intervention method and the cognitive neuroscience method.

The Effect of Peer Relationships on Adolescent Loneliness: The Role of Psychological Resilience and the OXTR Gene.

Background: Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). Methods: A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping. Results: The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness. Conclusion: These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.

A moderated mediation effects analysis was conducted to investigate the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). The results revealed psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.

The effect of life events on NSSI: the chain mediating effect of sleep disturbances and PLEs among Chinese college students.

This study aimed to explore the relationship between life events and non-suicidal self-injury (NSSI) in college students, as well as the mediating effect of sleep disturbances and psychotic-like experiences (PLEs). After excluding invalid questionnaires, 5,754 were retained, and the valid efficiency was 75.94%. The subjects were aged 16 to 29 years (M = 19.166; SD = 1.392), with 1,969 males (34.22%) and 3,785 females (65.78%). Life events, sleep disturbances, PLEs, and NSSI were assessed using standard scales. Data were analyzed by Pearson Correlation Analysis and bias-correction percentile Bootstrap method. The results show that (1) life events were significant positive predictors of NSSI, sleep disturbances, and PLEs; (2) sleep disturbances, PLEs, and the chain mediation between the two, were mediators between life events and NSSI. Life events are thus shown to be an important external factor influencing NSSI in university students, and this process is mediated through sleep disturbances, PLEs, and the chain between the two. Interventions for NSSI can therefore be made by improving college students' sleep quality and reducing PLEs.

The relationship between family functioning and psychotic-like experiences of college students: Chain multiple mediating effects.

AIM: To explore the mechanism of the relationship between college students' family functioning and psychotic-like experiences, a chain multi-intermediary model is constructed to investigate the multiple mediating effects of interpersonal adaptation, sleep quality and loneliness on college students' family functioning and psychotic-like experiences. METHODS: Seven hundred seven college students in China were surveyed by using the Family Care Index Questionnaire, Loneliness Scale, Pittsburgh Sleep Quality Index Questionnaire, College Students' Interpersonal Adaptability Subscale and Community Assessment of Psychiatric Experiences. RESULTS: (a) The detection rate of psychotic-like experiences among college students is 72.14%, of which 6.93% reported frequent psychotic-like experiences; (b) There is a significant correlation between family functioning, sleep quality, loneliness, interpersonal adaptation and psychotic-like experiences of college students; (c) Interpersonal adaptation, loneliness and sleep quality of college students have chain multiple mediating effect in the relationship between family functioning and psychotic-like experiences. CONCLUSION: The results reveal the mechanism of the relationship between family functioning and psychotic-like experiences, which helps us to better understand how family functioning affects the occurrence and development of college students' psychotic-like experiences.

Serotonergic multilocus genetic variation moderates the association between interpersonal relationship and adolescent depressive symptoms.

BACKGROUND: Research suggests that genetic variants linked to serotonin functioning moderate the association between environmental stressors and depressive symptoms, but examining gene-environment interactions with single polymorphisms limits power. METHODS: A multilocus genetic profile score (MGPS) approach to measuring serotonergic multilocus genetic variation and examined interactions with interpersonal relationship, insomnia with depressive symptoms as outcomes in an adolescent sample (average age = 14.15 ± 0.63 years since first measurement; range: 13 to 15). RESULTS: (1) interpersonal relationship predicted adolescent depressive symptoms; (2) insomnia mediated the effect of interpersonal relationships on adolescent depressive symptoms; (3) the THP2 gene rs4570625 polymorphism G allele was a key risk factor for depressive symptom, and the MGPS moderated the effects of teacher-student relationship and insomnia on adolescent depressive symptom. Specifically, as the MGPS increased, the effects of insomnia on adolescent depressive symptom were enhanced; further, when the MGPS score increased, the effect of teacher-student relationship on depression showed a similar phenomenon with an increased slope and enhanced prediction; and (4) the results of sensitivity analysis showed that multilocus genetic interaction with the environment had a better explanatory power and stability for depression than single polymorphism studies. CONCLUSION: MGPS provides substantial power to examine gene-environmental interactions linked to affective outcomes among adolescents.

The Relationship of Family Functioning and Suicidal Ideation among Adolescents: The Mediating Role of Defeat and the Moderating Role of Meaning in Life.

OBJECTIVE: To investigate the relationship between family functioning and suicidal ideation among adolescents. METHOD: A total of 4515 junior and senior high school students were assessed using the Family APGAR, the Depressive Symptom Index-Suicidality Subscale, the Defeat Scale, and the Chinese Meaning in Life Questionnaire. RESULTS: This study found pairwise correlations between suicidal ideation, family functioning, defeat, and meaning in life. Specifically, family functioning was an influencing factor of adolescent suicidal ideation, and defeat was a mediator of the relationship between family functioning and adolescent suicidal ideation; meaning in life was found to be a moderator of the first half of the mediation process by defeat, that is, it moderated the influence of family functioning on adolescent defeat. CONCLUSIONS: This study demonstrated that the relationship between family functioning and adolescent suicidal ideation, as well as the influence of defeat and meaning in life on this relationship, constituted a moderated intermediary model. This finding has both theoretical and practical value for the implementation of a psychosocial model of adolescent suicide prevention and intervention.

Determination of adenosine and its modifications in urine and plasma from breast cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers. 2'-O-methyladenosine (Am), N1-methyladenosine (m1A), N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am) and N6,N6-dimethyladenosine (m62A) are important adenosine (A) modifications. The noninvasive collection of urine samples and the diverse contents of metabolites in plasma make them favored biofluids for biomarkers discovery. In this work, we established a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method to quantify these six nucleosides in urine and plasma of healthy controls and breast cancer (BC) patients. The limit of detection (LOD) for A, Am, m1A, m6A, m6Am, and m62A were 0.0025, 0.01, 0.05, 0.005, 0.005, and 0.005 nM. The results showed that the concentrations of Am, m6A, and m6Am were increased, whereas m1A was decreased in the urine of BC patients compared with the healthy controls. We also found that the level ratios of m1A/A, m6A/A, and m6Am/A were all reduced in plasma from BC patients, compared with healthy controls. Interestingly, these ratios of methylated adenosine nucleosides to adenosine in plasma could better discriminate BC patients from healthy controls, compared to the levels of these nucleosides. The present study not only suggests these modified adenosines can act as noninvasive biomarkers of BC but also will contribute to investigating the impacts of RNA methylation on the occurrence and development of BC.

Oxidatively Damaged Nucleic Acid: Linking Diabetes and Cancer.

Significance: Our current knowledge of the mechanism between diabetes and cancer is limited. Oxidatively damaged nucleic acid is considered a critical factor to explore the connections between these two diseases. Recent Advances: The link between diabetes mellitus and cancer has attracted increasing attention in recent years. Emerging evidence supports that oxidatively damaged nucleic acid caused by an imbalance between reactive oxygen species generation and elimination is a bridge connecting diabetes and cancer. 8-Oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine assume important roles as biomarkers in assessing the relationship between oxidatively damaged nucleic acid and cancer. Critical Issues: The consequences of diabetes are extensive and may lead to the occurrence of cancer by influencing a combination of factors. At present, there is no direct evidence that diabetes causes cancer by affecting a single factor. Furthermore, the difficulty in controlling variables and differences in detection methods lead to poor reliability and repeatability of results, and there are no clear cutoff values for biomarkers to indicate cancer risk. Future Directions: A better understanding of connections as well as mechanisms between diabetes and cancer is still needed. Both diabetes and cancer are currently intractable diseases. Further exploration of the specific mechanism of oxidatively damaged nucleic acid in the connection between diabetes and cancer is urgently needed. In the future, it is necessary to further take oxidatively damaged nucleic acid as an entry point to provide new ideas for the diagnosis and treatment of diabetes and cancer. Experimental drugs targeting the repair process of oxidatively generated damage require an extensive preclinical evaluation and could ultimately provide new treatment strategies for these diseases. Antioxid. Redox Signal. 37, 1153-1167.

Simultaneous Determination of Methylated Nucleosides by HILIC-MS/MS Revealed Their Alterations in Urine from Breast Cancer Patients.

RNA methylation plays a vital role in the pathogenesis of a variety of diseases including cancer, and aberrant levels of modified nucleosides in RNA were revealed to be related to cancer. Urine is a favored source for biomarker discovery due to the non-invasion to patients. Herein, we developed a sensitive hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method combined with stable isotope dilution for accurate quantification of methylated nucleosides in human urine. With this method, we successfully quantified ten methylated nucleosides in urine samples collected from healthy controls and breast cancer patients. We found N6-methyladenosine (m6A), 2'-O-methyladenosine (Am), N1-methyladenosine (m1A), N6,2'-O-dimethyladenosine (m6Am), N1-methylguanosine (m1G), 2'-O-methylguanosine (Gm), 5-methylcytidine (m5C) and 2'-O-methylcytidine (Cm) were all decreased in early-stage breast cancer patients, and a nomogram prediction model was constructed. Locally advanced breast cancer patients exhibited elevated levels of urinary 2'-O-methylated nucleosides in comparison to early-stage breast cancer patients. Together, we developed a robust method for the simultaneous determination of methylated nucleosides in human urine, and the results revealed an association between the contents of urinary methylated nucleosides and the occurrence of breast cancer, which may stimulate future studies about the regulatory roles of these methylated nucleosides in the initiation and progression of breast cancer.

The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer.

As the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

Characterizing Oligomeric Hydroxyl Silicon Oils by MALDI-TOF MS With the Pyridine-Modified Matrix.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) is a powerful technique for analysis of various polymers, but it is still very difficult to characterize silicone oil due to its poor ionization efficiency. In this work, oligomeric hydroxyl silicone oils were successfully characterized by MALDI-TOF, by using pyridine-modified 2,5-dihydroxylbenzoic acid (DHB) as the matrix. Furthermore, the mixed crystal of DHB and hydroxyl silicone oil was analyzed by scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS), and the analytical results verified that modification with pyridine could remarkably improve the solubility of hydroxyl silicone oil in DHB, leading to the enhancement of its ionization efficiency in MALDI. The analysis of the MS spectra of a series of hydroxyl silicone oils indicated that they tended to be ionized by the attachment with Na+, and the average molecular weight and the degree of polymerization were measured for several oligomeric hydroxyl silicon oils.

Quantitative Analysis of Methylated Adenosine Modifications Revealed Increased Levels of N 6-Methyladenosine (m6A) and N 6,2'-O-Dimethyladenosine (m6Am) in Serum From Colorectal Cancer and Gastric Cancer Patients.

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N 6-methyladenosine (m6A), N 1-methyladenosine (m1A), 2'-O-methyladenosine (Am), N 6,2'-O-dimethyladenosine (m6Am), and N 6,N 6-dimethyladenosine (m6 2A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann-Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.

Mass Spectrometry-Based Targeted Serum Monomethylated Ribonucleosides Profiling for Early Detection of Breast Cancer.

RNA methylation plays a significant regulatory role in various of physiological activities and it has gradually become a hotspot of epigenetics in the past decade. 2'-O-methyladenosine (Am), 2'-O-methylguanosine (Gm), 2'-O-methylcytidine (Cm), 2'-O-methyluridine (Um), N 6-methyladenosine (m6A), N 1-methylguanosine (m1G), 5-methylcytidine (m5C), and 5-methyluridine (m5U) are representative 2'-O-methylation and base-methylation modified epigenetic marks of RNA. Abnormal levels of these ribonucleosides were found to be related to various diseases including cancer. Serum is an important source of biofluid for the discovery of biomarkers, and novel tumor biomarkers can be explored by measuring these ribonucleoside modifications in human serum. Herein, we developed and applied a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method to determine the content of monomethylated ribonucleosides in human serum. The developed method enabled sensitive and accurate determination of these monomethylated ribonucleosides. By applying this robust method, we demonstrated the presence of Gm and Um in human serum for the first time, and we successfully quantified m6A, Gm, m1G, Cm, Um and m5U in serum samples collected from 61 patients with breast cancer and 69 healthy controls. We discovered that the levels of Gm, m1G, Cm, Um and m5U in serum were all significantly decreased in breast cancer patients whereas m6A was increased. We performed receiver operating characteristic (ROC) curve analysis, and obtained highest area under curve (AUC) value when combining these six monomethylated ribonucleosides together. These results suggest that m6A, Gm, m1G, Cm, Um and m5U might have great potential to be novel biomarkers for detection of breast cancer in the early stage. In addition, this study may stimulate future investigations about the regulatory roles of monomethylated ribonucleosides on the initiation and development of breast cancer.

Examining the Link Between Academic Achievement and Adolescent Bullying: A Moderated Moderating Model.

PURPOSE: Bullying is a serious problem among adolescents. Many scholars have examined school bullying in recent years; however, there are many psychological and behavioral mechanisms for bully that still remain unclear. Based on the theory of self-worth orientation, this study examined the influence of academic achievement on bullying behavior among adolescents and explored the moderating effects of perceived social support and age cohort. METHODS: Participants were 3227 middle and high school students in the 7th through 12th grades in China. A self-report method was used to measure academic achievement, social support, bullying, and demographic variables. RESULTS: Moderation analyses indicated that the relationship between academic achievement and bullying behavior was moderated by the perceived social support of adolescents and their age cohort. Specifically, social support moderated the relationship between achievement and bullying behavior positively in the middle school group but negatively in the high school group. CONCLUSION: The results support the hypothesis of self-worth orientation theory and indicate that bullying intervention could be enhanced by addressing the relationships between academic achievement, social support, age cohort, and bullying.

8-Hydroxyguanosine as a possible RNA oxidative modification marker in urine from colorectal cancer patients: Evaluation by ultra performance liquid chromatography-tandem mass spectrometry.

Oxidative RNA damage has been found to be associated with a variety of diseases, and 8-hydroxyguanosine (8-OHG) is a typical marker of oxidative modification of RNA. This guanosine modification is an emerging biomarker for disease detection and determination of 8-OHG in human urine is favored because it is noninvasive to patients. However, due to its poor ionization efficiency in mass spectrometry and trace amount in urine, accurate quantification of this modified nucleoside is still challenging. Herein, a rapid, accurate, sensitive and robust method using solid-phase extraction (SPE) combined with isotope dilution ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for detection of this oxidative RNA modification in human urine. The limit of detection can reach 1.5 fmol and the method exhibits good precision on intra-day (1.8-3.3%) and inter-day (0.6-1.2%) analyses. Satisfactory recovery (87.5-107.2%) at three spiked levels was achieved by using HLB cartridge for urine pretreatment. Using this method, we quantified 8-OHG in urine from 65 colorectal cancer (CRC) patients and 76 healthy volunteers. The measured level of urinary 8-OHG for CRC patients and healthy controls is 1.91 ± 0.63 nmol/mmol creatinine and 1.33 ± 0.35 nmol/mmol creatinine, respectively. We found the content of 8-OHG in urine was raised in CRC patients patients, implying this oxidative RNA modification marker could act as a potential noninvasive indicator for early screening of CRC. In addition, this study will make contributions to the investigations of the influences of oxidative stress on the formation and development of CRC.