Fatalism and Suicidal Behaviors Among Chinese College Students: The Mediating Role of Depressive Symptoms and the Moderating Role of Coping Strategies.

The aim of this study was to investigate the relationship between fatalism and suicidal behaviors, the mediating role of depressive symptoms, and the moderating effect of coping strategies on the mediating process. A total of 519 participants completed the Multidimensional Fatalism Scale for General Life Events, the Center for Epidemiologic Studies-Depression scale, the Simplified Coping Style Questionnaire, and the Suicidal Behaviors Questionnaire-Revised. Results suggest that depressive symptoms partially mediated the relationship between fatalism and suicidal behaviors. Active coping moderated the mediating effect of depressive symptoms. The higher the active coping level, the weaker the mediating effect. The findings revealed that the mechanism of fatalism affecting suicidal behaviors, and had theoretical and empirical value for the prevention and intervention of suicide among college students.

Outcome expectations and working alliance may be more important for patients from rural areas during the transition to college life: An exploratory within-patient analysis.

OBJECTIVE: Research has given limited attention to the distinction between patients from rural and urban areas, especially concerning the frequent overlap between rural living and low socio-economic status (SES). To shed more light on this, we explored the differential treatment processes between patients from rural and urban areas. METHOD: Seven hundred and fourteen patients recruited from a university counseling center in China filled out the questionnaires for Outcome Expectation (OE), Session Alliance Inventory (SAI) and Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) each session. Data was analyzed using the disaggregated cross-lagged panel model and the asymmetric fixed-effect model. RESULTS: The findings indicated a reciprocal within-patient relation between OE and SAI for the whole sample. SAI mediated the effect of OE on next-session CORE-OM for patients from rural areas, with a significantly greater indirect effect than for patients from the urban areas. Asymmetric effects were found for OE among patients from urban areas, for whom drops in OE predicted worse next-session CORE-OM more strongly than improvements in OE predicted improved CORE-OM. CONCLUSION: This study provided preliminary evidence for differential OE-alliance-outcome predictions between patients with different SES and affirmed a reciprocal OE-alliance relation in a Chinese sample during the transition period of college.

Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma.

The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α-a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention.

Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following recombination-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.

Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following homology-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.

BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network.

Inhibition of the tumour suppressive function of p53 (encoded by TP53) is paramount for cancer development in humans. However, p53 remains unmutated in the majority of cases of glioblastoma (GBM)-the most common and deadly adult brain malignancy1,2. Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53WT) GBM is unknown. Here we describe a GBM-specific epigenetic mechanism in which the chromatin regulator bromodomain-containing protein 8 (BRD8) maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex. This mechanism causes a repressive chromatin state that prevents transactivation by p53 and sustains proliferation. Notably, targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility and engages p53 transactivation. This in turn enforces cell cycle arrest and tumour suppression in TP53WT GBM. In line with these findings, BRD8 is highly expressed with H2AZ in proliferating single cells of patient-derived GBM, and is inversely correlated with CDKN1A, a canonical p53 target that encodes p21 (refs. 3,4). This work identifies BRD8 as a selective epigenetic vulnerability for a malignancy for which treatment has not improved for decades. Moreover, targeting the bromodomain of BRD8 may be a promising therapeutic strategy for patients with TP53WT GBM.

Childhood maltreatment influences suicidal behavior: Rumination mediates and regulatory emotional self-efficacy moderates.

To investigate the mediating role of rumination in the association between childhood maltreatment and suicidal behavior, and the moderating role of regulatory emotional self-efficacy, university students (N = 1,458) from 5 universities in China completed questionnaires in classrooms. Path analyses showed emotional maltreatment had the greatest positive association with suicidal behavior and rumination compared with other types of childhood maltreatment. Rumination partly mediated the relationship between childhood maltreatment and suicidal behavior. High regulatory emotional self-efficacy moderated the relation between ruminating childhood maltreatment and suicidal behavior.

EZH2 regulates a SETDB1/ΔNp63α axis via RUNX3 to drive a cancer stem cell phenotype in squamous cell carcinoma.

Enhancer of zeste homolog 2 (EZH2) and SET domain bifurcated 1 (SETDB1, also known as ESET) are oncogenic methyltransferases implicated in a number of human cancers. These enzymes typically function as epigenetic repressors of target genes by methylating histone H3 K27 and H3-K9 residues, respectively. Here, we show that EZH2 and SETDB1 are essential to proliferation in 3 SCC cell lines, HSC-5, FaDu, and Cal33. Additionally, we find both of these proteins highly expressed in an aggressive stem-like SCC sub-population. Depletion of either EZH2 or SETDB1 disrupts these stem-like cells and their associated phenotypes of spheroid formation, invasion, and tumor growth. We show that SETDB1 regulates this SCC stem cell phenotype through cooperation with ΔNp63α, an oncogenic isoform of the p53-related transcription factor p63. Furthermore, EZH2 is upstream of both SETDB1 and ΔNp63α, activating these targets via repression of the tumor suppressor RUNX3. We show that targeting this pathway with inhibitors of EZH2 results in activation of RUNX3 and repression of both SETDB1 and ΔNp63α, antagonizing the SCC cancer stem cell phenotype. This work highlights a novel pathway that drives an aggressive cancer stem cell phenotype and demonstrates a means of pharmacological intervention.

BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas.

Bromodomain containing protein 4 (BRD4) plays a critical role in controlling the expression of genes involved in development and cancer. Inactivation of BRD4 inhibits cancer growth, making it a promising anticancer drug target. The cancer stem cell (CSC) population is a key driver of recurrence and metastasis in patients with cancer. Here we show that cancer stem-like cells can be enriched from squamous cell carcinomas (SCC), and that these cells display an aggressive phenotype with enhanced stem cell marker expression, migration, invasion, and tumor growth. BRD4 is highly elevated in this aggressive subpopulation of cells, and its function is critical for these CSC-like properties. Moreover, BRD4 regulates ΔNp63α, a key transcription factor that is essential for epithelial stem cell function that is often overexpressed in cancers. BRD4 regulates an EZH2/STAT3 complex that leads to increased ΔNp63α-mediated transcription. Targeting BRD4 in human SCC reduces ΔNp63α, leading to inhibition of spheroid formation, migration, invasion, and tumor growth. These studies identify a novel BRD4-regulated signaling network in a subpopulation of cancer stem-like cells, elucidating a possible avenue for effective therapeutic intervention. SIGNIFICANCE: This study identifies a signaling cascade driven by BRD4 that upregulates ΔNp63α to promote cancer stem-like properties, which has potential therapeutic implications for the treatment of squamous cell carcinomas.

Alliance-outcome relation and progress feedback: Secondary data analyses of a randomized clinical trial study in China.

Objective: This study examined the alliance-outcome relation and the possible moderation effect of receiving progress feedback on a sample of Chinese clients. Method: One hundred and fifty-nine clients recruited from a university counseling center in central China filled out the Session Rating Scale (SRS) and the Outcome Rating Scale (ORS) each session. Participants were randomly assigned to either the progress feedback group or non-feedback group. Therapists working with clients in the feedback group received their clients' SRS and ORS scores weekly and were asked to plot their scores in a chart. The alliance-outcome and moderator effects were tested with disaggregated cross-lagged panel modeling of SRS and ORS. Results: The findings indicated a strong reciprocal relation between SRS and ORS, but the moderator effect due to feedback was not supported. Conclusion: Results affirm the cross-cultural stability of the session-by-session reciprocal effects of the alliance-outcome model in a Chinese sample. The issue of whether feedback moderates the within-person alliance-outcome relationship needs to be studied further.

Ligand-controlled cobalt-catalyzed regiodivergent hydroboration of aryl,alkyl-disubstituted internal allenes.

We report a stereoselective regiodivergent hydroboration of aryl,alkyl-disubstituted internal allenes with pinacolborane (HBpin) in the presence of cobalt catalysts generated from bench-stable Co(acac)2 and bisphosphine ligands. An interesting correlation between the regioselectivity of this hydroboration and the bite angles of bisphosphine ligands was identified. When hydroboration was conducted with cobalt catalysts containing bisphosphines with medium bite angles (e.g. 98° for dppb and 96° for dppf), HBpin was selectively added to the alkyl-substituted double bond. However, HBpin was selectively added to the aryl-substituted double bond when the reactions were conducted with cobalt catalysts containing bisphosphines with large bite angles (e.g. 111° for xantphos and 114° for Nixantphos). A range of internal allenes underwent these Co-catalyzed hydroboration reactions in a regiodivergent manner to yield the corresponding (Z)-alkenylboronates in high isolated yields and with high regioselectivity. These reactions show good functional group compatibility and can be readily scaled up to gram scales without using a dry box. In addition, the comparison of regioselectivity between the Co-catalyzed hydrosilylation and hydroboration reactions of the same allene substrate suggests that this Co-catalyzed regiodivergent hydroboration of allenes proceeds through a Co-Bpin intermediate. Deuterium-labeling experiments suggest that the Co-Bpin intermediates react with allenes to form allylcobalt species which then react with HBpin to release (Z)-alkenylboronate products.

A study of the epidemiology and risk factors for attempted suicide and suicide among non-psychiatric inpatients in 48 general hospitals in Hubei province, China, 2015-2017.

OBJECTIVE: This was a large-scale epidemiological survey of non-psychiatric inpatient attempted suicides/suicides in general hospitals in China, allowing a detailed quantitative analysis of the characteristics of inpatient attempted suicides/suicides. METHODS: The incidence, inpatient demographic and behavioral characteristics, and risk factors for attempted suicide/suicide were explored through a survey of non-psychiatric inpatients admitted to 48 general hospitals, between 2015 and 2017. A Vector Error Correction model was established to explore hospital variables as predictors of inpatient attempted suicide/suicide using the annual numbers of inpatient attempted suicides/suicides, undergraduate or above nurses per total number of nurses, and number of beds per nurse in a tertiary general hospital, between 1998 and 2017. RESULTS: The incidence of attempted suicide/suicide among inpatients in general hospitals was 3.26/100,000 admissions. 180 inpatient attempted suicides/suicides were reported, which were associated with particular inpatient demographic and behavioral characteristics and a specific temporal and spatial distribution. Incidence of attempted suicide/suicide was higher in inpatients aged ≥60 years, with junior high school or lower level of education, in secondary general hospitals, suffering from malignant tumors or chronic diseases. Number of beds/nurse had a significant impact on the incidence of inpatient attempted suicide/suicide. CONCLUSION: We recommend that general hospital administrators establish a targeted approach to inpatient suicide prevention efforts in their hospitals.

Pd/Cu-Catalyzed Enantioselective Sequential Heck/Sonogashira Coupling: Asymmetric Synthesis of Oxindoles Containing Trifluoromethylated Quaternary Stereogenic Centers.

An asymmetric palladium and copper co-catalyzed Heck/Sonogashira reaction between o-iodoacrylanilides and terminal alkynes to synthesize chiral oxindoles was developed. In particular, a wide range of CF3 -substituted o-iodoacrylanilides reacted with terminal alkynes, affording the corresponding chiral oxindoles containing trifluoromethylated quaternary stereogenic centers in high yields with excellent enantioselectivities (94-98 % ee). This asymmetric Heck/Sonogashira reaction provides a general approach to access oxindole derivatives containing quaternary stereogenic centers including CF3 -substituted ones.

ATRX loss induces telomere dysfunction and necessitates induction of alternative lengthening of telomeres during human cell immortalization.

Loss of the histone H3.3-specific chaperone component ATRX or its partner DAXX frequently occurs in human cancers that employ alternative lengthening of telomeres (ALT) for chromosomal end protection, yet the underlying mechanism remains unclear. Here, we report that ATRX/DAXX does not serve as an immediate repressive switch for ALT. Instead, ATRX or DAXX depletion gradually induces telomere DNA replication dysfunction that activates not only homology-directed DNA repair responses but also cell cycle checkpoint control. Mechanistically, we demonstrate that this process is contingent on ATRX/DAXX histone chaperone function, independently of telomere length. Combined ATAC-seq and telomere chromatin immunoprecipitation studies reveal that ATRX loss provokes progressive telomere decondensation that culminates in the inception of persistent telomere replication dysfunction. We further show that endogenous telomerase activity cannot overcome telomere dysfunction induced by ATRX loss, leaving telomere repair-based ALT as the only viable mechanism for telomere maintenance during immortalization. Together, these findings implicate ALT activation as an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction.

Cobalt-Catalyzed Enantioselective Hydroboration/Cyclization of 1,7-Enynes: Asymmetric Synthesis of Chiral Quinolinones Containing Quaternary Stereogenic Centers.

An asymmetric cobalt-catalyzed hydroboration/cyclization of 1,7-enynes to synthesize chiral six-membered N-heterocyclic compounds was developed. A variety of aniline-tethered 1,7-enynes react with pinacolborane to afford the corresponding chiral boryl-functionalized quinoline derivatives in high yields with high enantioselectivity. This cobalt-catalyzed asymmetric cyclization of 1,7-enyens provides a general approach to access a series of chiral quinoline derivatives containing quaternary stereocenters.

Client feedback in China: A randomized clinical trial in a college counseling center.

Although client feedback has been demonstrated to improve psychotherapy outcomes in over a dozen randomized clinical trials, no studies to date have investigated the feedback effect outside of the United States or Europe. This study examined the impact of a client feedback intervention, the Partners for Change Outcome Management System, in a college counseling center in Wuhan, China (N = 186). Using a randomized design within routine care, treatment as usual (TAU; n = 85) was compared with a feedback condition (n = 101) in which therapists had access to client-generated outcome and alliance information at each session. Clients in the feedback condition demonstrated significantly greater improvement than those in the TAU condition at posttreatment. Not-on-track (n = 60) clients also demonstrated significantly more improvement at 6 times the rate of reliable change compared with the TAU condition. Survival analysis revealed that 66.7% of the clients in the feedback condition achieved reliable and clinically significant change after a median of 4 sessions whereas 57.0% of the clients in the TAU condition achieved reliable and clinically significant change after a median of 6 sessions. Alliance scores improved significantly more across treatment and were higher at posttreatment in the feedback condition. Although preliminary, this study suggests that the positive effects of improved outcomes and increased efficiency associated with systematic client feedback can also occur in a college counseling setting in China. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Cobalt-Catalyzed Asymmetric Hydroboration/Cyclization of 1,6-Enynes with Pinacolborane.

We report a cobalt-catalyzed asymmetric hydroboration/cyclization of 1,6-enynes with catalysts generated from Co(acac)2 and chiral bisphosphine ligands and activated in situ by reaction with pinacolborane (HBpin). A variety of oxygen-, nitrogen-, and carbon-tethered 1,6-enynes underwent this asymmetric transformation, yielding both alkyl- and vinyl-substituted boronate esters containing chiral tetrahydrofuran, cyclopentane, and pyrrolidine moieties with high to excellent enantioselectivities (86%-99% ee).

Effects of life satisfaction and psychache on risk for suicidal behaviour: a cross-sectional study based on data from Chinese undergraduates.

OBJECTIVES: To examine predictive power of psychache and life satisfaction on risks for suicidal ideation and suicide attempt among young people. DESIGN: A cross-sectional study. SETTING: Data were collected from an online survey in Wuhan, China. PARTICIPANTS: 5988 university students from six universities were selected by a stratified cluster sampling method. PRIMARY AND SECONDARY OUTCOME MEASURES: Suicidal ideation and suicide attempt at some point of the students' lifetime were the outcomes of interest. RESULTS: Students with suicidal ideation or attempted suicide reported a lower level of life satisfaction and high degree of psychache than counterparts without suicidal ideation or attempt. Regression analyses indicated that life satisfaction and psychache were significantly associated with the risk of suicidal ideation and the risk of suicidal attempt. Though psychache showed a relatively stronger predictive power than life satisfaction, the effect of the two factors remained significant when they were individually adjusted for personal demographic characteristics. However, when the two factors were included in the model simultaneously to adjust for each other, psychache could fully explain the association between life satisfaction and suicidal attempt. Life satisfaction remained to contribute unique variance in the statistical prediction of suicidal ideation. CONCLUSIONS: Psychache and life satisfaction both have a significant predictive power on risk for suicidal behaviour, and life satisfaction could relieve the predictive power of psychache when suicidal behaviour is just starting. Shneidman's theory that psychache is the pre-eminent psychological cause of suicide is perhaps applicable only to a more serious form of suicidal behaviour.

Direct (het)arylation of fluorinated benzothiadiazoles and benzotriazole with (het)aryl iodides.

A new and controllable method for the preparation of unsymmetrical and symmetrical fluorinated benzothiadiazole (FBT)-arene structures that can be applied in organic optoelectronic materials has been developed. The reaction proceeds under mild reaction conditions with high efficiency and shows excellent functional group compatibility, even toward bromide. Fluorinated benzotriazoles also take part in the reaction.

Thioether-promoted direct olefination of polyfluoroarenes catalyzed by palladium.

A methyl(phenyl)sulfane-promoted direct olefination of polyfluoroarenes catalyzed by palladium has been reported. With use of this new thioether ligand, a high reaction efficiency and excellent E/Z ratio of desired olefinated polyfluoroarenes were obtained. This represents a first example of thioether promoted oxidative Heck reaction.