Brain structural alterations associated with impulsiveness in male violent patients with schizophrenia.

BACKGROUND: Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis. METHOD: The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence. RESULTS: The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group. CONCLUSION: Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ.

Multidimensional Electrochemistry Decodes the Operando Mechanism of Hydrogen Oxidation.

Being an efficient approach to the utilization of hydrogen energy, the hydrogen oxidation reaction (HOR) is of particular significance in the current carbon-neutrality time. Yet the mechanistic picture of the HOR is still blurred, mostly because the elemental steps of this reaction are rapid and highly entangled, especially when deviating from the thermodynamic equilibrium state. Here we report a strategy for decoding the HOR mechanism under operando conditions. In addition to the wide-potential-range I-V curves obtained using gas diffusion electrodes, we have applied the AC impedance spectroscopy to provide independent and complementary kinetic information. Combining multidimensional data sources has enabled us to fit, in mathematical rigor, the core kinetic parameter set in a 5-D data space. The reaction rate of the three elemental steps (Tafel, Heyrovsky, and Volmer reactions), as a function of the overpotential, can thus be distilled individually. Such an undocumented kinetic picture unravels, in detail, how the HOR is controlled by the elemental steps on polarization. For instance, at low polarization region, the Heyrovsky reaction is relatively slow and can be ignored; but at high polarization region, the Heyrovsky reaction will surpass the Tafel reaction. Additionally, the Volmer reaction has been the fastest within overpotentials of interest. Our findings not only offer a better understanding of the HOR mechanism, but also lay the foundation for the development of improved hydrogen energy utilization systems.

LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and frequent cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) play regulatory roles and serve as biomarkers of multiple cancers, including ESCC. Our previous studies have confirmed that lncRNA Kinectin 1 antisense RNA 1 (KTN1-AS1) is highly expressed in ESCC and exerts oncogene function through RBBP4/HDAC1 complex. OBJECTIVE: Our present study focused on exploring a novel molecular mechanism of KTN1-AS1 in ESCC. METHODS: In this study, qRT-PCR assay, Western blot assay, Luciferase reporter assay, and RNA immunoprecipitation assay were conducted. RESULTS: We found that KTN1-AS1 could bind to miR-885-5p in ESCC cells, and miR-885-5p was low expressed in ESCC. Overexpression of miR-885-5p inhibited esophageal cancer cells proliferation and invasion in vitro. Mechanistic analysis demonstrated that miR-885-5p specifically targeted striatin 3 (STRN3), and KTN1-AS1/miR-885-5p promoted the EMT process by Hippo pathway in STRN3/YAP1 dependent manner. CONCLUSION: To sum up, KTN1-AS1 facilitates ESCC progression by acting as a ceRNA for miR-885-5p to regulate STRN3 expression and the Hippo pathway, and KTN1-AS1 maybe used as a promising therapeutic target for ESCC.

FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with poor prognosis, necessitating identification of oncogenic mechanisms for novel therapeutic strategies. Recent studies have highlighted the significance of the transcription factor forkhead box K1 (FOXK1) in diverse biological processes and carcinogenesis of multiple malignancies, including ESCC. However, the molecular pathways underlying FOXK1's role in ESCC progression are not fully understood, and its potential role in radiosensitivity remains unclear. Here, we aimed to elucidate the function of FOXK1 in ESCC and explore the underlying mechanisms. Elevated FOXK1 expression levels were found in ESCC cells and tissues, positively correlated with TNM stage, invasion depth, and lymph node metastasis. FOXK1 markedly enhanced the proliferative, migratory and invasive capacities of ESCC cells. Furthermore, silencing FOXK1 resulted in heightened radiosensitivity by impeding DNA damage repair, inducing G1 arrest, and promoting apoptosis. Subsequent studies demonstrated that FOXK1 directly bound to the promoter regions of CDC25A and CDK4, thereby activating their transcription in ESCC cells. Moreover, the biological effects mediated by FOXK1 overexpression could be reversed by knockdown of either CDC25A or CDK4. Collectively, FOXK1, along with its downstream target genes CDC25A and CDK4, may serve as a promising set of therapeutic and radiosensitizing targets for ESCC.

Reciprocal regulation of LINC00941 and SOX2 promotes progression of esophageal squamous cell carcinoma.

LINC00941 is a novel long noncoding RNA (lncRNA) and emerging as an important factor in cancer development. However, the exact function and relative regulatory mechanism of LINC00941 in carcinogenesis of esophageal squamous cell carcinoma (ESCC) remain to be further clarified. The present study was to investigate the expression level, functions, and mechanisms of LINC00941 in ESCC tumorigenesis. LINC00941 was significantly upregulated in ESCC, and upregulated LINC00941 was correlated with dismal patient outcomes. LINC00941 functioned as an oncogene by promoting cells proliferation, stemness, migration, and invasion in ESCC. In terms of mechanisms, SOX2 could bind directly to the promoter region of LINC00941 and activate its transcription. In turn, LINC00941 upregulated SOX2 through interacting with interleukin enhancer binding factor 2 (ILF2) and Y-box binding protein 1 (YBX1) at the transcriptional and post-transcriptional levels. LINC00941 recruited ILF2 and YBX1 to the promoter region of SOX2, leading to upregulation of the transcription of SOX2. Moreover, LINC00941 could promote the binding ability of ILF2 and YBX1 on mRNA of SOX2 and further stabilize SOX2 mRNA. Therefore, LINC00941 contributed to the malignant behaviors of ESCC cells via the unrestricted increase in SOX2 expression. In conclusion, our data indicate that LINC00941 exacerbates ESCC progression through forming a LINC00941-ILF2/YBX1-SOX2 positive feedback loop, and LINC00941 may be a promising prognostic and therapeutic target for ESCC.

Methylation Mediated Downregulation of TOB1-AS1 and TOB1 Correlates with Malignant Progression and Poor Prognosis of Esophageal Squamous Cell Carcinoma.

BACKGROUND: TOB1, a member of the transducer of erbB-2 /B-cell translocation gene family, was detected to be down-regulated in ESCC by RNA sequencing. TOB1-AS1, a head-to-head antisense lncRNA with TOB1, was down-regulated in several cancers. However, the roles of them in esophageal squamous cell carcinoma (ESCC) remained unclarified. AIMS: To investigate the roles and functions of TOB1-AS1 and TOB1 in ESCC tumorigenesis. MATERIALS AND METHODS: The expression levels, methylation status, biological function and mechanisms of TOB1-AS1 and TOB1 in ESCC were, respectively, detected. RESULTS: Frequent down-regulation of TOB1-AS1 and TOB1 was verified in esophageal cancer cells and ESCC tissues, and there was a positive correlation between them in ESCC tissues. The CpG sites hypermethylation within proximal promoter of TOB1-AS1 and TOB1 could lead to transcriptional inhibition of both genes. Furthermore, expression and proximal promoter methylation status of TOB1-AS1 or TOB1 may be associated with ESCC patients' prognosis. TOB1-AS1 and TOB1 may function as tumor suppressors by inhibiting growth, migration, and invasion of esophageal cancer cells. Up-regulation of TOB1-AS1 increased expression level of TOB1, and TOB1-AS1 could work as a ceRNA to modulate ATF3 expression via competitively binding with miR-103a-2-5p. Meanwhile, ATF3, as a transcription factor, could regulate transcription of TOB1; down-regulation of TOB1-AS1 in ESCC led to decreased expression of ATF3 through ceRNA mechanism, and further influenced the transcription of TOB1. CONCLUSION: TOB1-AS1 and TOB1 may act as tumor suppressors and may serve as potential targets for antitumor therapy in ESCC.

KTN1-AS1, a SOX2-mediated lncRNA, activates epithelial-mesenchymal transition process in esophageal squamous cell carcinoma.

Kinectin 1 antisense RNA 1 (KTN1-AS1), a long non-coding RNA (lncRNA), has been proved to have tumor-promoting properties and its expression is enhanced in several human tumors. However, the role of KTN1-AS1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC) remains unknown. This study aimed to investigate the expression status, functional roles, and molecular mechanisms of KTN1-AS1 in the development of ESCC. Considerable upregulation of KTN1-AS1 was confirmed in esophageal cancer cells and ESCC tissues and its expression was associated with TNM stage, pathological differentiation, and lymph node metastasis. SOX2 directly activated transcription of KTN1-AS1, and overexpression of KTN1-AS1 facilitated ESCC cells proliferation and invasion in vitro and in vivo. Furthermore, KTN1-AS1 could bind to retinoblastoma binding protein 4 (RBBP4) in the nucleus and enhanced its binding with histone deacetylase 1 (HDAC1), thereby activating the epithelial-mesenchymal transition (EMT) process through downregulating E-cadherin expression at the epigenetic level. In conclusion, KTN1-AS1, induced by SOX2, acts as a tumor-promoting gene and may serve as a potential therapeutic and prognostic biomarker for ESCC.

The clinical prognostic value of long noncoding RNA HAND2-AS1 in cancer patients: A study based on meta-analysis and TCGA data (PRISMA).

BACKGROUND: The heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) is a novel long noncoding RNA aberrantly expressed in human malignancies. We aimed to analyze the available data to evaluate the clinical prognostic significance of HAND2-AS1 in tumors. METHODS: In this meta-analysis, electronic databases, including PubMed Cochrane Library, EMBASE, Medline, Web of Science, CNKI, and Wanfang, were searched from their inception up to December 1, 2021. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the relationship of HAND2-AS1expression level with prognosis and clinicopathological features in cancer patients. The publication bias was identified by Begg's test, and the sensitivity analysis was also performed. RESULTS: A total of 10 articles with 615 patients were included in the present meta-analysis. The combined results revealed that low expression of HAND2-AS1 was associated with poor overall survival (OS) (HR = 0.48, 95% CI: 0.36-0.64, P < .001) in a variety of cancers. In addition, the decrease in HAND2-AS1 expression was also correlated with poor differentiation (OR = 4.36, 95% CI: 2.15-8.87, P < .001) and lymph node metastasis (OR = 0.26, 95% CI: 0.13-0.54, P < .001). The cancer genome atlas (TCGA) dataset further demonstrated that low expression of HAND2-AS1 was associated with poor OS and disease-free survival. CONCLUSIONS: Our results of this meta-analysis indicated that HAND2-AS1 may be a prognostic marker and even a therapeutic target for human cancer.

Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1.

Aberrant expression of long non-coding RNAs (lncRNAs) plays pivotal roles in tumorigenesis of human malignant cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific role of lncRNA NRSN2-AS1 in ESCC has not been investigated. Our analysis of clinical data revealed that NRSN2-AS1 was upregulated in ESCC tissues and negatively correlated with patient survival. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NRSN2-AS1 is transcribed by SOX2. In vitro functional experiments showed that NRSN2-AS1 can promote ESCC cell proliferation, migration, and invasion. Furthermore, NRSN2-AS1-binding proteins were detected using RNA pull-down assays and mass spectrometry. Mechanistically, NRSN2-AS1 can bind to phosphoglycerate kinase 1 (PGK1) and upregulate its protein levels by inhibiting its ubiquitination. Knockdown of PGK1 in part abolished the NRSN2-AS1 overexpression-induced effects on ESCC cell proliferation, migration, invasion, and epithelial­mesenchymal transition (EMT). Thus, NRSN2-AS1 may be a diagnostic biomarker or treatment target for ESCC.

E2F1-activated NRSN2 promotes esophageal squamous cell carcinoma progression through AKT/mTOR pathway.

BACKGROUND: Neurensin­2 (NRSN2) has been reported to act as an oncogene in several types of human cancer. However, the molecular mechanism of NRSN2 in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. METHODS: The mRNA expression levels of NRSN2 in ESCC tissues and cell lines were evaluated by quantitative real-time PCR (qRT-PCR). The protein expression levels of NRSN2 in ESCC tissues were measured by Immunohistochemical (IHC) method. Luciferase reporter and chromatin immunoprecipitation assays were conducted to confirm the upstream transcription factor of NRSN2. Loss- and gain-function assays were conducted to evaluate the effects of NRSN2 on ESCC cells proliferation, migration, and invasion. The function of NRSN2 was validated in vivo using tumor xenografts. The relationship between NRSN2 and AKT/mTOR pathway were confirmed by western blot assay. RESULTS: The expression level of NRSN2 was increased in ESCC tissues and cell lines. High expression level of NRSN2 was correlated with depth of invasion, lymph node metastasis, TNM stage, and poor prognosis of ESCC patients. NRSN2 was transcribed by E2F1. Knockdown of NRSN2 significantly inhibited ESCC cells proliferation, migration, and invasion, whereas NRSN2 overexpression showed reverse phenotypes. Overexpression of NRSN2 also enhanced ESCC tumorigenicity in vivo. Furthermore, the E2F1/NRSN2 axis promoted proliferation, migration, and invasion of ESCC cells by activating the AKT/mTOR pathway. CONCLUSION: NRSN2 is a direct transcriptional target of E2F1 to promote tumor progression in ESCC. NRSN2 may be a diagnostic biomarker or treatment target for ESCC.

Structural Deficits in the Frontotemporal Network Associated With Psychopathic Traits in Violent Offenders With Schizophrenia.

People with schizophrenia (SZ) are at increased risk of violence compared to the general population. However, the neural mechanisms of violent behavior in patients with SZ are still unclear due to the heterogeneity of the diseased population. In this study, we aimed to examine the neural correlates of violent behavior in SZ and to determine whether the structural deficits were related to psychopathic traits. A total of 113 participants, including 31 SZ patients with violent behavior (vSZ), 39 SZ patients without violent behavior (nvSZ), and 43 healthy controls (HC), completed the T1-weighted magnetic resonance imaging (MRI) scan and were analyzed using voxel-based morphometry approach. The psychopathic traits were assessed using the Psychopathy Checklist: Screening Version (PCL:SV). The results showed decreased gray matter volume (GMV) in the vSZ group in the right temporal lobe and bilateral inferior frontal gyri compared to HCs; while reduced GMV in the inferior parietal lobe, parahippocampal and orbital frontal gyri was found in the nvSZ group compared with HCs. Correlation analyses showed that psychopathic traits were negatively associated with the GMV in the right superior temporal and left fusiform gyri in the vSZ group, indicating that psychopathic traits, as reflected by the score of antisocial factor, might be related to structural deficits in the temporal lobe, which led to a propensity to violent behavior in patients with SZ. Our findings suggest that violent behavior in patients with SZ might have a personality background associated with the frontotemporal network aberrance. In future studies, we need to take a closer look at psychopathic traits for better understanding of the mechanism of interpersonal violence in patients with SZ and to explore whether the imaging findings from this study can serve as a biomarker to predict future violent behaviors and community living.

Preanodized Cu Surface for Selective CO2 Electroreduction to C1 or C2+ Products.

The electrochemical CO2 reduction over Cu catalysts has shown great potential in producing a wide range of valuable chemicals, but it is still plagued by a poor controllability on product distribution. Herein, we demonstrate an effective regulation of CO2 reduction paths through a preanodization treatment of Cu foil electrodes in different electrolytes. The Cu electrode exhibits a superior C1 and C2+ product selectivity after being preanodized in NaClO4 (Cu-NaClO4) and Na2HPO4 electrolyte (Cu-Na2HPO4), respectively. Combined with in situ electrochemical Raman, ATR-SEIRAS, and SEM characterizations, the preferential C1 path is due to the deposition of many Cu nanocrystals with dominant Cu(111) facets on the Cu-NaClO4 electrode. In contrast, the preferential C2+ path over the Cu-Na2HPO4 is attributed to formation of a unique Cu nanodendritic morphology, which strengthens the *CO intermediate adsorption and induces an environment of low local H2O/CO2 stoichiometric ratio, thus facilitating C-C coupling for C2+ production. Our findings may shed light on the rational control of the CO2 reduction path through engineering of the Cu surface structure.

Downregulation of LINC00886 facilitates epithelial-mesenchymal transition through SIRT7/ELF3/miR-144 pathway in esophageal squamous cell carcinoma.

LINC00886 has been reported to be down-regulated in laryngeal squamous cell carcinoma, and aberrant DNA methylation status of it has been screened in several tumor types. However, the roles of LINC00886 in esophageal squamous cell carcinoma (ESCC) remained unclarified. The present study was to investigate the expression level, epigenetic inactivation mechanisms, and functions of LINC00886 in ESCC tumorigenesis. Frequent down-regulation of LINC00886 was verified in esophageal cancer cells and ESCC tissues. There are CpG islands spanning the promoter and exon 1 regions of LINC00886 gene, and DNA hypermethylation of proximal promoter led to transcriptional inhibition of LINC00886, moreover, histone modification also played certain roles in LINC00886 transcription. LINC00886 functioned as a tumor suppressor by inhibiting proliferation, migration, and invasion of esophageal cancer cells. LINC00886 was down-regulated following TGF-ß1 treatment in esophageal cancer cells and participated in epithelial-mesenchymal transition (EMT) process by regulating EMT-related genes, especially ZEB1 and ZEB2. ELF3 was proved to be one of the downstream target genes of LINC00886. LINC00886 may interact with and recruit SIRT7 to decrease acetylation level of H3K18 on the promoter region of ELF3 to inhibit its expression. Furthermore, ELF3 may promote EMT process via promoting ZEB1 and ZEB2 expression through binding to the promoter region of miR-144 to suppress miR-144-3p transcriptional activity in ESCC. These data suggest that LINC00886 may act as a tumor suppressor gene in ESCC and its down-regulation through epigenetic mechanisms promotes EMT process via SIRT7/ELF3/miR-144 pathway in ESCC. Thus, LINC00886 may be a potential therapeutic target for ESCC treatment.

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia.

BACKGROUND/AIMS: The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. METHODS: A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn's & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. RESULTS: In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn's disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. CONCLUSIONS: The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages.

Background and Aim: Interleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages. Methods: We assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots. Results: Compared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn's disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages. Conclusion: Compared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.

Development and validation of a nomogram for prediction of cervical lymph node metastasis in middle and lower thoracic esophageal squamous cell carcinoma.

BACKGROUND: Estimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction. METHODS: A total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use. RESULTS: Totally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762-0.905), 0.808 (95% CI 0.696-0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: We developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC.

Identification of violent patients with schizophrenia using a hybrid machine learning approach at the individual level.

Despite numerous risk factors associated with violence in patients with schizophrenia, predicting and preventing violent behavior is still a challenge. At present, machine learning (ML) has become a promising strategy for guiding individualized assessment. To build an effective model to predict the risk of violence in patients with schizophrenia, we proposed a hybrid ML method to improve the prediction capability in 42 violent offenders with schizophrenia and 33 non-violent patients with schizophrenia. The results revealed that the final model, which combined multimodal data, achieved the highest prediction performance with an accuracy of 90.67%. Specifically, the model, which fused three modalities of neuroimaging data, achieved a better accuracy than other fused models. In addition, the msot discriminative neuroimaging features involved in the prefrontal-temporal cognitive circuit and striatum reward system, indicating that dysfunction in cortical-subcortical circuits might be associated with high risk of violence in patients with schizophrenia. This study provides the first evidence supporting that the combination of specific multimodal neuroimaging and clinical data in ML analysis can effectively identify violent patients with schizophrenia. Furthermore, this work is crucial for the development of neuro-prediction models that could facilitate individualized treatment and interventions for violent behaviors in patients with schizophrenia.

Self-Harm History, Anxiety-Depression, Severity of Disease, and Insight Are Significantly Associated With Suicide Risk in Forensic Psychiatric Inpatients of China.

Background: Forensic psychiatric patients have higher suicide risk than the general population. This study aimed to evaluate the extent of suicide risk and to explore the associated factors in forensic psychiatric inpatients in China. Methods: We conducted a cross-sectional study from 1st November, 2018 to 30th January, 2019 in the Forensic Psychiatric Hospital of Hunan Province, China. Patient's information on socio-demographic, clinical, and criminological characteristics was collected. The suicidality subscale of the MINI-International Neuropsychiatric Interview (M.I.N.I.), the Brief Psychiatric Rating Scale (BPRS), and the Severity of Illness of Clinical Global Impressions Scale (CGI-SI) were used to measure present suicide risks, psychiatric symptoms, and the severity of the patient's disease, respectively. Binary logistic regression models were used to examine factors associated with suicide risk. Results: Twenty-one percent (84/408) of the forensic psychiatric inpatients reported suicide risk. Logistic regression analysis suggested that self-harm history (OR:3.47, 95% confidence interval CI: 1.45-8.33), symptoms of anxiety-depression (OR:1.15, 95% CI:1.04-1.27), and more severe mental disorder (OR:1.42, 95% CI:1.08-1.87) were associated with elevated suicide risk, while insight disorder (OR:0.81, 95% CI:0.65-0.99) was related to decreasing suicide risk. Conclusion: The study supplied useful clinical information to recognize high suicide risk in forensic psychiatric inpatients and may aid the development of valuable strategies for preventing and reducing suicide events.

FOXD3 suppresses epithelial-mesenchymal transition through direct transcriptional promotion of SMAD7 in esophageal squamous cell carcinoma.

The transcription factor forkhead box D3 (FOXD3) is an important member of the FOX family, which can maintain the pluripotent properties of cell clusters, neural crest, and trophoblastic progenitor cells in vivo. It has been shown that FOXD3 could affect proliferation, migration, and angiogenesis of various tumors and its deletion and overexpression in organisms will undoubtedly have important influence on the change of cell fate and the occurrence of tumors. However, the underlying functions and molecular mechanisms of FOXD3 in esophageal squamous cell carcinoma (ESCC) have not been fully clarified. According to the present study, the expression levels and functional roles of FOXD3 were investigated, and its prognostic value and molecular mechanisms in tumorigenesis and progression of ESCC were clarified. The expression level of FOXD3 was significantly downregulated in ESCC tissues and cell lines, and correlated with gender, family history of upper gastrointestinal cancer, TNM stage, depth of invasion, lymph node metastasis, and ESCC patients' survival. Moreover, FOXD3 inhibited cells migration and invasion as well as participated in TGF-ß1 induced epithelial-mesenchymal transition process. Furthermore, a positive correlation between FOXD3 and SMAD family member 7 (SMAD7) was explored in ESCC. FOXD3 could directly bind to promoter regions of SMAD7 gene, leading to transcriptional promotion of SMAD7 in human esophageal cancer cells. Taken together, FOXD3 may play a tumor suppressor role in ESCC and may be applied as a new therapeutic target and prognostic marker for ESCC.

LINC00239 Interacts with C-Myc Promoter-Binding Protein-1 (MBP-1) to Promote Expression of C-Myc in Esophageal Squamous Cell Carcinoma.

Increasing evidence demonstrates that long non-coding RNAs (lncRNA) play a vital role in the progression of tumors, containing esophageal squamous cell carcinoma (ESCC). LINC00239 was reported as an oncogene in diverse kinds of cancers, whereas its specific role is still unclear in ESCC. In this study, we detected the expression and functional role of LINC00239 in ESCC specimens and cells, and investigated the molecular mechanisms of it. LINC00239 was highly expressed in ESCC tissues and cells, and was related to poor prognosis of patients with ESCC. The proliferation, metastasis, and invasion ability as well as epithelial-mesenchymal transition (EMT) process were all enhanced in LINC00239-overexpressed ESCC cells. LINC00239 was upregulated in TGF-ß1-treated ESCC cells. Furthermore, LINC00239 was found to bind directly to the transcription factor c-Myc promoter-binding protein-1 (MBP-1). MBP-1 was detected to inhibit the transcription of c-Myc in ESCC. Moreover, LINC00239 could activate c-Myc transcription through influencing MBP-1-binding ability to c-Myc promoter. These data suggest that LINC00239 may act as an oncogene to promote the transcription of c-Myc by competitively combining with MBP-1 in ESCC, and may serve as a potential target for antitumor therapy in ESCC. IMPLICATIONS: LINC00239 may function as an oncogenic lncRNA in ESCC through the LINC00239/MBP-1/c-Myc axis to activate EMT process.