The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation.

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.

Mechanism of electroconvulsive therapy in schizophrenia: a bioinformatics analysis study of RNA-seq data.

OBJECTIVE: The molecular mechanism of electroconvulsive therapy (ECT) for schizophrenia remains unclear. The aim of this study was to uncover the underlying biological mechanisms of ECT in the treatment of schizophrenia using a transcriptional dataset. METHODS: The peripheral blood mRNA sequencing data of eight patients (before and after ECT) and eight healthy controls were analyzed by integrated co-expression network analysis and the differentially expressed genes were analyzed by cluster analysis. Gene set overlap analysis was performed using the hypergeometric distribution of phypfunction in R. Associations of these gene sets with psychiatric disorders were explored. Tissue-specific enrichment analysis, gene ontology enrichment analysis, and protein-protein interaction enrichment analysis were used for gene set organization localization and pathway analysis. RESULTS: We found the genes of the green-yellow module were significantly associated with the effect of ECT treatment and the common gene variants of schizophrenia ( P  = 0.0061; family-wise error correction). The genes of the green-yellow module are mainly enriched in brain tissue and mainly involved in the pathways of neurotrophin, mitogen-activated protein kinase and long-term potentiation. CONCLUSION: Genes associated with the efficacy of ECT were predominantly enriched in neurotrophin, mitogen-activated protein kinase and long-term potentiation signaling pathways.

Electroconvulsive Therapy Reduces Protein Expression Level of EP300 and Improves Psychiatric Symptoms and Disturbance of Thought in Patients with Schizophrenia.

Objective: Although electroconvulsive therapy (ECT) has been employed as an effective treatment strategy and to improve mental symptoms in schizophrenia (SCZ), its action mechanisms remain unclear. Our previous study found that some genes and biological pathways were closely related to ECT through genetic technology analysis, such as LTP pathway and EP300. This study combined with healthy controls and symptomatology analysis to further explore the changes of expression of EP300 protein in treatment and related symptoms of SCZ. Methods: One hundred and one patients with SCZ and 45 healthy controls (HCs) were enrolled in this study. Patients with SCZ received acute courses of 6 times bilateral ECT. The peripheral blood of patients with SCZ (BECT: before ECT; AECT: after ECT) and the HCs was collected to calculate the changes of expression level of EP300 protein by enzyme-linked immunosorbent assay. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate the severity of symptoms of SCZ patients and the efficiency of the ECT. Results: There was a statistical difference of EP300 protein expression in patients with SCZ (BECT and AECT) (F = 114.5, p < 0.05). ECT reduced plasma expression level of EP300 protein in patients with SCZ, which was not statistically different from that in HCs (t = 4.47, p = 0.20). The change of the expression level of EP300 protein in patients with SCZ (BECT and AECT) has a positive correlation with reduction rate of positive symptoms (r = 0.228, p < 0.05) and disturbance of thought (r = 0.219, p < 0.05). Conclusion: Our study suggests that the expression level of EP300 protein has a significant change in patients with SCZ treating with ECT, and EP300 may have some connections with positive symptoms and disturbance thought of patients with SCZ.

Enhanced Pavlovian-to-instrumental transfer in internet gaming disorder.

Background and aims: The Pavlovian-to-instrumental transfer (PIT) effect is a phenomenon that Pavlovian conditioned cues that could influence one's instrumental behavior. In several substance and behavioral addictions, such as tobacco use disorder and gambling disorder, addiction-related cues could promote independently trained instrumental drug-seeking/drug-taking behaviors, indicating a specific PIT effect. However, it is unclear whether Internet gaming disorder (IGD) would show a similar change in PIT effects as other addictions. The study aimed to explore the specific PIT effects in IGD. Methods: We administrated a PIT task to individuals with IGD (n = 40) and matched health controls (HCs, n = 50), and compared the magnitude of specific PIT effects between the two groups. The severity of the IGD symptoms was assessed by the Chinese version 9-item Internet Gaming Disorder Scale (IGDS) and the Internet Addiction Test (IAT). Results: We found that: (1) related to the HCs group, the IGD group showed enhanced specific PITgame effects, where gaming-related cues lead to an increased choice rate of gaming-related responses; (2) in the IGD group, the magnitude of specific PITgame effects were positively correlated with IAT scores (rho = 0.39, p = 0.014). Discussion and Conclusions: Individuals with IGD showed enhanced specific PIT effects related to HCs, which were associated with the severity of addictive symptoms. Our results highlighted the incentive salience of gaming-related cues in IGD.

Brain structural alterations in internet gaming disorder: Focus on the mesocorticolimbic dopaminergic system.

AIMS: This study aimed to identify gray/white matter volume (GMV/WMV) alterations in Internet Gaming Disorder (IGD), with a special focus on the subregions of the mesocorticolimbic dopaminergic system and their clinical association. RESULTS: Compared with healthy controls, IGDs showed bigger GMV in the bilateral caudate and the left nucleus accumbens (NAc), and bigger WMV in the inferior parietal lobule. The comparison of regions of interest (ROI) confirmed increased GMV in the bilateral caudate (including the dorsal anterior, body, and tail) and the left core of NAc in IGD, but no significant WMV alterations in the mesocorticolimbic dopaminergic system. GMVs in the left lateral orbital gyrus of orbitofrontal cortex (OFC) were associated with craving for games, while GMVs in the left anterior insula, right NAc, right caudate, and right OFC were associated with self-control in IGD. CONCLUSIONS: IGD was accompanied by changed GMV, but not WMV, in the mesocorticolimbic dopaminergic system. GMV in the mesocorticolimbic dopaminergic system may contribute to impaired self-control and craving in IGD.

A Phase I Study to Evaluate the Pharmacokinetic Drug‒Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia.

BACKGROUND AND OBJECTIVE: HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor that is being developed for the treatment of hyperuricemia and gout. The primary aim of the present study was to study the pharmacokinetic drug‒drug interactions (DDIs) of HP501, febuxostat, and colchicine in hyperuricemic patients. METHODS: Hyperuricemic patients were randomly divided into group A, receiving HP501 40 mg once daily on days 1 and 4-10, and group B, receiving febuxostat 40 mg once daily on day 1 and HP501 40 mg plus febuxostat 40 mg on days 4-10. All patients received 0.5 mg colchicine once daily from day 4 to 12. Blood samples were collected for measurement of drug concentrations and serum uric acid (sUA) levels. RESULTS: Coadministration of colchicine with HP501 or HP501 plus febuxostat did not affect steady-state exposure to colchicine. Coadministration of HP501 and febuxostat did not significantly change the pharmacokinetic profiles of either drug. Following multiple administrations of HP501 40 mg once daily for 7 days, the maximal percent sUA change from baseline in group A was - 24.77%. The coadministration of HP501 40 mg and febuxostat 40 mg in group B for 7 days resulted in a - 55.82% maximal sUA reduction from baseline, and all patients achieved the goal of sUA < 360 µmol/L. All adverse events (AEs) were either mild or moderate, and the most frequently reported AEs were diarrhea and elevated alanine aminotransferase (ALT) levels. CONCLUSIONS: The concomitant use of HP501, febuxostat, and colchicine did not produce clinically meaningful DDIs in terms of their pharmacokinetic properties. CLINICAL TRIAL REGISTRATION: No. CTR20212261 ( http://www.chinadrugtrials.org.cn/ ) registered September 2021.

Correlation between duration of untreated psychosis and long-term prognosis in chronic schizophrenia.

Objective: To explore the relationship between the Duration of Untreated Psychosis (DUP) and long-term clinical outcome, cognitive and social function in patients with chronic schizophrenia (SCZ). Methods: A total of 248 subjects with chronic SCZ were enrolled in this study, including 156 in the short DUP group and 92 in the long DUP group. The Positive and Negative Symptoms Scale (PANSS), the Brief Negative Symptoms Scale (BNSS), the Global Assessment of Functioning (GAF) scale and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess all of the subjects. Results: The negative symptom scores (the PANSS and BNSS) of subjects with long DUP were significantly higher than that in subjects with short DUP. The scores of visual span and speech function in the short DUP group were significantly higher, indicative of decreasing cognitive function with time. In terms of social function, the short DUP group scored higher, with a statistically significant difference. Meanwhile, we found that the length of DUP was positively correlated with the negative symptom score of the PANSS, negatively correlated with visual span scores, and GAF scores. Conclusion: This study demonstrated that the DUP remained a significant association with negative symptom and cognition in long period of chronic SCZ.

Initial validation of the Chinese version VIA Youth-96 and age-related changes in character strengths among adolescents.

This study aimed to preliminary examine the psychometric properties of the Chinese version 96-item VIA Inventory for Youth (VIA Youth-96) by analyzing the internal consistency, factorial validity, and criterion validity, and to examine the age-related changes in character strengths (CSs) among adolescents. The sample consisted of 959 adolescents aged 10-17 (49.5% boys). Participants completed the Chinese version VIA Youth-96, along with the Perceived Parental Autonomy Support Scale, and questionnaires assessing life satisfaction and self-efficacy online. The Chinese version VIA Youth-96 showed a good fit for the original four-factor structure, and CS scores were significantly correlated with life satisfaction and self-efficacy indicating a good criterion validity of the scale. The internal consistency was 0.54-0.86 for subscales. Moreover, this study revealed significant age-related changes in CSs among adolescents, eight CSs significantly linearly declined by age. These results suggested that the Chinese version VIA Youth-96 is a valid tool for assessing CSs in adolescents and that CSs are declined linearly by age during adolescence.

Demographic characteristics, family environment and psychosocial factors affecting internet addiction in Chinese adolescents.

BACKGROUND: Internet addiction of adolescents has aroused social concern recently. The present study aims to identify predicting factors of internet addiction on adolescents. METHODS: The demographic characteristics and psychological characteristics of 50, 855 middle school students were investigated through Internet Gaming Disorder Scale- Short Form(IGDS9-SF), Smartphone Application-Based Addiction Scale (SABAS), Bergen Social Media Addiction Scale (BSMAS), Strengths and Difficulties Questionnaire-students (SDQS), 16-Item Version of the Prodromal Questionnaire (PQ-16), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Multidimensional Peer Victimization Scale (MPVS), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), and Connor-Davidson Resilience Scale (CD-RISC10) were used to analyze factors associated with internet addiction by Pearson correlation coefficient and multiple hierarchical regression. RESULTS: IGDS9-SF, SABAS and BSMAS are positively correlated with SDQS, PQ-16, PHQ-9, GAD-7 and MPVS (r-values ranging from 0.180 to 0.488, p < 0.01). IGDS9-SF, SABAS and BSMAS are negatively correlated with WEMWB and CD-RISC (r-values ranging from -0.242 ~ -0.338, p < 0.01). Multiple hierarchical regression shown gender, one-child, twins, left-behind, rural, education (father), drink (father), smoke (father), CD-RISC-10, SDQS, PQ-16, PHQ-9, GAD-7 and MPVS predicted 32.7 % of the variance in internet gaming disorder (IGD) (F = 1174.949, p < 0.001). Group (junior and senior), Gender, Age, One-Child, Twins, Village, Education (father), Drink (father), Drink (mother), Smoke (father), WEMWBS, CD-RISC-10, SDQS, PQ-16, PHQ-9, GAD-7 and MPVS predicted 28.9 % of the total variance in social media addiction (SMA) (F = 982.932, p < 0.001). Fifteen variables [Gender, Age, Twins, Left-behind, Residence, Residence, Education (mother), Drink(father), Drink (mother), Smoke (father), WEMWBS, CD-RISC-10, PHQ-9, GAD-7 and MPVS] predicted 30.7 % of the variance in smartphone addiction (SA) (F = 1076.02, p < 0.001). CONCLUSION: The present study found that demographic characteristics, family environment and psychosocial factors were associated with internet gaming addiction, social media addiction and smartphone addiction. Negative psychological factors (such as anxiety and depression) play an important role in different behavioral addictions.

Altered spontaneous brain activity in major depressive disorder: An activation likelihood estimation meta-analysis.

BACKGROUND: Wide application of resting-state functional magnetic resonance imaging (fMRI) in psychiatric research has revealed that major depressive disorder (MDD) manifest abnormal neural activities in several brain regions involving key resting state networks. However, inconsistent results have hampered our understanding of the exact neuropathology associated with MDD. Therefore, our aim was to conduct a meta-analysis to identify the consistent vulnerable brain regions of MDD in resting state, and to reveal the potential pathogenesis of MDD. METHODS: A systematic review analysis was conducted on studies involving brain resting-state changes in MDD using low-frequency amplitude (ALFF), fractional low-frequency amplitude (fALFF) and regional homogeneity (ReHo) analysis. The meta-analysis was based on the activation likelihood estimation method, using the software of Ginger ALE 2.3. RESULTS: 25 studies (892 MDD and 799 healthy controls) were included. Based on the meta-analysis results of ReHo, we found robust reduction of resting-state spontaneous brain activity in MDD, including the left cuneus and right middle occipital gyrus (cluster size = 216, 256 mm3, uncorrected P < 0.0001), while no increased spontaneous activation in any of the brain regions. We also found reduced ALFF in the left middle occipital gyrus (cluster size = 224 mm3, uncorrected P < 0.0001), and no increased spontaneous brain activation in any regions. CONCLUSION: Our meta-analysis study using the activation likelihood estimation method demonstrated that MDD showed significant abnormalities in spontaneous neural activity, compared with healthy controls, mainly in areas associated with visual processing, such as the cuneus and the middle occipital gyrus. Dysfunction of these brain regions may be one of the pathogenesis of MDD.

Character strengths as protective factors against behavior problems in early adolescent.

Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10-12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r = -0.14 to -0.3, p < 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14-22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution (ß = -0.34 to -0.14 for self-regulation, perseverance, zest, humility, and leadership; ß = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.

Implicit measure of suicidal ideation in patients with depression.

The death/suicide implicit association test (IAT) may be more resilient to accurately assess suicide risk than self-reports. We examined the IAT in 130 patients with depression and 125 healthy controls, along with self-reported suicidal ideation. IAT could differentiate patients with suicide attempts from patients without suicide attempts and controls. IAT measures were significantly correlated to explicit suicidal ideation and clinical symptoms in patients. Moreover, the IAT-symptom correlations were significant in female but not male patients. The IAT showed promise as a valid tool to estimate suicide risk in patients with depression and may be particularly useful in female patients.

Blunted reward prediction error signals in internet gaming disorder.

BACKGROUND: Internet gaming disorder (IGD) is a type of behavioural addictions. One of the key features of addiction is the excessive exposure to addictive objectives (e.g. drugs) reduces the sensitivity of the brain reward system to daily rewards (e.g. money). This is thought to be mediated via the signals expressed as dopaminergic reward prediction error (RPE). Emerging evidence highlights blunted RPE signals in drug addictions. However, no study has examined whether IGD also involves alterations in RPE signals that are observed in other types of addictions. METHODS: To fill this gap, we used functional magnetic resonance imaging data from 45 IGD and 42 healthy controls (HCs) during a reward-related prediction-error task and utilised a psychophysiological interaction (PPI) analysis to characterise the underlying neural correlates of RPE and related functional connectivity. RESULTS: Relative to HCs, IGD individuals showed impaired reinforcement learning, blunted RPE signals in multiple regions of the brain reward system, including the right caudate, left orbitofrontal cortex (OFC), and right dorsolateral prefrontal cortex (DLPFC). Moreover, the PPI analysis revealed a pattern of hyperconnectivity between the right caudate, right putamen, bilateral DLPFC, and right dorsal anterior cingulate cortex (dACC) in the IGD group. Finally, linear regression suggested that the connection between the right DLPFC and right dACC could significantly predict the variation of RPE signals in the left OFC. CONCLUSIONS: These results highlight disrupted RPE signalling and hyperconnectivity between regions of the brain reward system in IGD. Reinforcement learning deficits may be crucial underlying characteristics of IGD pathophysiology.

Character strengths as protective factors against behavior problems in early adolescent

Character strengths could efectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10­12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r = −0.14 to −0.3, p < 0.05 Bonferroni corrected). Character strengths explained a signifcant proportion of additional variance (14­22%) in fve types of behavior problems after controlling the efect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specifc character strengths showed an independent contribution (ß = −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership; ß = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character trengths were protective factors against behavior problems in early adolescents.

Sleep duration and auditory hallucinations: Genetic correlation and two-sample Mendelian randomization study.

OBJECTIVES: Previous studies have found that sleep problems are associated with psychotic experiences (PEs) across clinical designs, but many confounding factors from uncertain variables have been unclear in observational designs. The aim of the present study was to detect the genetic correlations and causal relationship between sleep-related traits and PEs using the largest current genome-wide association study (GWAS) summary statistics. METHODS: GWAS results were obtained for positive PEs (N = 116,787-117,794) and sleep-related traits [insomnia complaints (N = 386,533), morningness (N = 345,552), sleep duration (N = 384,317), ease of getting up in the morning (N = 385,949), daytime napping (N = 386,577), daytime sleepiness (N = 386,548), and snoring (N = 359,916)]. Linkage disequilibrium score regression (LDSC) was used to investigate genetic correlations. Mendelian randomization (MR) was conducted on trait pairs with significant genetic associations. RESULTS: We found that auditory hallucinations were significantly genetically correlated with insomnia complaints (rg = -0.27, p = 1.1 × 10-3), sleep duration (rg = 0.21, p = 9.7 × 10-3), and ease of getting up (rg = 0.31, p = 2 × 10-4). Visual hallucinations and insomnia complaints were highly genetically correlated (rg = 0.36, p = 6.4 × 10-5). Mendelian randomization indicated a unidirectional causal relationship between sleep duration with auditory hallucinations (ß = -0.93, p = 7.9 × 10-4 for sleep duration as the exposure). We used large GWAS summary statistics across the LDSC and MR programs to determine that sleep duration as exposure to increase the risk of auditory hallucinations. CONCLUSIONS: Taken together, these findings suggest that treatment of sleep problems should be considered as a higher priority for future mental health services.

Transcriptome Sequencing Reveals the Potential Mechanisms of Modified Electroconvulsive Therapy in Schizophrenia.

OBJECTIVE: Schizophrenia (SCZ) is one of the most common and severe mental disorders. Modified electroconvulsive therapy (MECT) is the most effective therapy for all kinds of SCZ, and the underlying molecular mechanism remains unclear. This study is aim to detect the molecule mechanism by constructing the transcriptome dataset from SCZ patients treated with MECT and health controls (HCs). METHODS: Transcriptome sequencing was performed on blood samples of 8 SCZ (BECT: before MECT; AECT: after MECT) and 8 HCs, weighted gene co-expression network analysis (WGCNA) was used to cluster the different expression genes, enrichment and protein-protein interaction (PPI) enrichment analysis were used to detect the related pathways. RESULTS: Three gene modules (black, blue and turquoise) were significantly associated with MECT, enrichment analysis found that the long-term potentiation pathway was associated with MECT. PPI enrichment p-value of black, blue, turquoise module are 0.00127, <1×10-16 and 1.09×10-13, respectively. At the same time, EP300 is a key node in the PPI for genes in black module, which got from the transcriptome sequencing data. CONCLUSION: It is suggested that the long-term potentiation pathways were associated with biological mechanism of MECT.

Maladaptive metacognitive beliefs mediated the effect of intolerance of uncertainty on depression.

Both elevated intolerance of uncertainty (IU) and maladaptive metacognitive beliefs (MBs) were associated with depression. However, the relationship between MBs and IU in clinical depression is unclear. The current study aimed to investigate the putative impairment of MBs and IU in major depressive disorder (MDD) and explore the relationship between these two factors with depressive symptoms. Metacognition Questionnaire-30 Items (MCQ-30), Intolerance of Uncertainty Scale-Short Form (IUS-12) and clinical rating scales were administered to 53 patients with MDD and 56 healthy controls (HCs). Stepwise regressions were performed to explore independent contributions of MBs and IU on depression. Mediation analysis was used to examine associations among variables. Patients with MDD reported higher IUS-12 and MCQ-30 scores than HCs. Stepwise regressions revealed a unique contribution of negative MBs concerning the consequences of not controlling thoughts (MCQ-NC) on depression symptoms while controlling the effects of age, gender, anxiety symptoms and IU. MCQ-NC and negative MBs concerning the uncontrollability and danger of negative thinking (MCQ-NEG) completely mediated the effects of IU on depression and anxiety symptoms. Our results provided clear evidence that maladaptive negative MBs are directly associated with depression symptoms, and mediated the effect of IU on depression and anxiety symptoms, suggesting that IU and MBs influence clinical symptoms in a hierarchical manner.

Global research on cognitive behavioural therapy for schizophrenia from 2000 to 2019: a bibliometric analysis via CiteSpace.

BACKGROUND: Cognitive behavioural therapy (CBT) is considered to be an effective treatment for schizophrenia. In recent years, researchers have published clinical research results on CBT for schizophrenia. However, there is currently a lack of bibliometric analysis on CBT for schizophrenia. AIMS: To understand the current situation and research trends of CBT for schizophrenia, and to provide valuable information for researchers in this field. METHODS: Literature was retrieved from the Web of Science Core Collection database. CiteSpace was used to visually analyse the current status of research on CBT for schizophrenia, as well as trends and points of general interest on this topic. RESULTS: A total of 1151 papers were retrieved. The annual number of publications has increased 417.65% from 2000 to 2019. Schizophrenia Research was the most active journal. McGorry enjoys considerable influence. The University of London is deemed to be the most active research institution. England and the USA retain the highest scientific productivity in this field. China and Norway might make more contributions to this field in the future. The most important research topics are randomised controlled trials of CBT for schizophrenia, meta-analysis, scale selection and research on the improvement of quality of life. Results from the following keywords 'psychoeducation', 'insomnia', 'individual', 'mental illness', 'major depressive disorder', 'efficacy', 'internalised stigma' and 'remediation' indicated new research frontiers in this field. CONCLUSIONS: The field of CBT for schizophrenia is progressing and has great potential. The level and quality of research in this field is high. The proposal of research hotspots and frontiers serves as a direction for researchers in this field. Researchers around the world should strengthen their cooperation and communication to promote further development of this field.

Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion.

Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion. In the past few years, significant progress has been made in reprogramming and transdifferentiation of somatic cells with small molecule approaches. In the present review, we systematically discuss recent achievements of pure chemical reprogramming and transdifferentiation.