Diamond with Unexpected Multi-Scale Pores.

Following the diverse structural characteristics and primary usage, diamond products include nano-polycrystalline diamond (NPD), micron-polycrystalline diamond (MPD), diamond film, porous diamond, and diamond wire drawing die. Among them, porous diamond possesses a distinctive combination of flexible surface functionality and a remarkably high surface area-to-volume ratio (SA/V) compared to traditional bulk materials, which contributes to cross-cutting applications in catalysis, adsorption, and electrochemistry while retaining the superior traits of diamond, particularly its exceptional chemical inertia. To avoid etching or microwave plasma chemical vapor deposition (MPCVD) techniques, this study proposes a high-temperature and high-pressure method based on a soluble skeleton (HPHT-ss) as an efficient and inexpensive approach for synthesizing millimeter-level porous diamonds. Interestingly, porous diamond synthesized by HPHT-ss exhibits multiscale pores distributed as macropores (average 75 µm) and mesopores (average 19 nm), which gives it a unique feature compared with other methods. Pertinent temperature-pressure conditions, HPHT-ss synthesis, and the formation mechanism of porous diamonds are also thoroughly discussed.

Mechanical, Thermal Properties, and Extreme Phase Stability of High-Entropy Diborides (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2.

High-entropy diborides (HEDBs) have gained significant attention in industrial applications due to their vast composition space and tunable properties. We propose a solid solution reaction at high temperatures and pressures that successfully synthesized and sintered a novel, dense, and phase-pure HEDB (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2. A high asymptotic Vickers hardness of 26.3 ± 0.6 GPa and a bulk modulus of 320.5 ± 10.6 GPa were obtained. Additionally, we investigated the thermal oxidation process using TG-DSC from room temperature to 1500 °C and explored the phase stability of HEDBs under high-pressure conditions through in situ high-pressure synchrotron radiation X-ray diffraction. We analyzed the formation of lattice distortion, chemical bonding, and band structure in (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2 using first-principles calculations. Surprisingly, we found that the predominant distortion in diborides occurs in the boron layer, supported by ELF. This may be due to uneven electron transfer rather than a straightforward correlation with the atomic radius. These results provide a novel synthesis process and additional experimental data on the mechanical and thermal properties and high-pressure phase stability of HEDBs. Our study offers further insights into the microscopic structure of lattice distortion in HEDBs, which could prove crucial for the selection and design of engineering advanced HEDBs.

HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

RNA methylation-related inhibitors: Biological basis and therapeutic potential for cancer therapy.

RNA methylation is widespread in nature. Abnormal expression of proteins associated with RNA methylation is strongly associated with a number of human diseases including cancer. Increasing evidence suggests that targeting RNA methylation holds promise for cancer treatment. This review specifically describes several common RNA modifications, such as the relatively well-studied N6-methyladenosine, as well as 5-methylcytosine and pseudouridine (Ψ). The regulatory factors involved in these modifications and their roles in RNA are also comprehensively discussed. We summarise the diverse regulatory functions of these modifications across different types of RNAs. Furthermore, we elucidate the structural characteristics of these modifications along with the development of specific inhibitors targeting them. Additionally, recent advancements in small molecule inhibitors targeting RNA modifications are presented to underscore their immense potential and clinical significance in enhancing therapeutic efficacy against cancer. KEY POINTS: In this paper, several important types of RNA modifications and their related regulatory factors are systematically summarised. Several regulatory factors related to RNA modification types were associated with cancer progression, and their relationships with cancer cell migration, invasion, drug resistance and immune environment were summarised. In this paper, the inhibitors targeting different regulators that have been proposed in recent studies are summarised in detail, which is of great significance for the development of RNA modification regulators and cancer treatment in the future.

Marital status and living apart affect sleep quality in male military personnel: a study of the China's Navy during COVID-19.

Background: Marital status is a robust sociodemographic predictor of sleep. Having to live apart from spouse may have different implications than those of cohabitants or singles, especially in military personnel. Further research on this group will help provide knowledge in advance and facilitate early targeted interventions. Methods: An online questionnaire study was conducted from July to November 2021. A total of 1,832 male military personnel completed the questionnaire. The marital status was measured by a self-reported single choice question. Pittsburgh sleep quality index (PSQI), Epworth Sleepiness Scale (ESS) and The Dysfunctional Beliefs and Attitudes about sleep scale (DBAS-16) were used to measure sleep-related outcomes. Inverse probability weighting (IPW) was applied to reduce the effects of confounding. Logistic regression was used to analyze the relationship between marital status and sleep and explore the impact of living together or not. Results: After inverse probability weighting, the prevalence of poor sleep quality, sleepiness and dysfunctional beliefs were 16.1, 20.1 and 7.1%, respectively. One-way ANOVA results for the means of both groups were statistically significantly different, except for the sleep latency and sleep disturbance dimensions of PSQI. Participants who were married were more likely to have poor sleep quality (OR: 1.408, 95% CI: [1.10, 1.80]), to have daytime sleepiness (OR: 1.560, 95% CI: [1.27, 1.92]) and to develop dysfunctional beliefs and attitudes (OR: 2.497, 95% CI: [1.65, 3.80]) than those who were unmarried. Further analysis showed that the odds of developing poor sleep quality and DBAS in participants who married but living apart were significantly bigger than those unmarried (OR: 1.548 and 3.991, respectively.), while there were no significant differences in the odds of daytime sleepiness (OR: 0.738, p = 0.050). Age was a protective factor for the development of bad sleep outcomes, while family economic was an independent risk factor. Conclusion: Marital status appear important for sleep quality, daytime sleepiness and sleep beliefs. The effect of living apart or not should be considered separately as an important predictor of sleep.

Changes in sleep quality among Chinese active service personnel: A cross-temporal meta-analysis, 2003-2019.

Military personnel live in operating environments in which poor sleep is common. In this cross-temporal meta-analysis (CTMA), 100 studies (144 data sets, N = 75,998) were identified to examine changes in sleep quality among Chinese active service personnel from 2003 to 2019. Participants were divided into three groups: the navy, the non-navy, and the unknown service. The Pittsburgh Sleep Quality Index (PSQI) was used as the measure of sleep quality; it contains a global score and seven component scores, with higher scores indicative of poorer sleep. Among all active military personnel, the PSQI global and seven component scores decreased from 2003 to 2019. In examining the results by military type, the PSQI global and seven component scores increased in the navy group. Conversely, both the non-navy and unknown-service groups showed decreased PSQI global scores over time. Similarly, all PSQI component scores decreased over time for both the non-navy and unknown service groups, except for the use of sleeping medication (USM), which increased in the non-navy group. In conclusion, the sleep quality of Chinese active service personnel showed a positive trend. Further research should focus on improving the navy's sleep quality.

microRNA-497 slows esophageal cancer development and reverses chemotherapy resistance through its target QKI.

Esophageal cancer (EC) is considered one of the most lethal cancers in human beings, and multiple miRNAs have been investigated to be involved in EC development by targeting their target genes. However, the function and related mechanism of miRNA-497 on EC tumorigenesis remain uncertain. This study first demonstrated that the expression levels of miR-497 in esophageal cancer specimens and cells were down-regulated. Forced expression of miR-497 inhibited cell proliferation, tube formation and migration in EC cells. To further investigate the potential molecular mechanism of miR-497 suppression in regulating EC, we found that miR-497 directly binds to the 3'-untranslational region of QKI, miR-497 overexpression suppressed QKI expression. We further found that overexpression of miR-497 enhanced the effect of chemotherapy in EC cell lines, and prevented the tumor growth of EC in vivo. Our findings indicated that miR-497 suppression increased QKI expression and therapeutic resistance of esophageal cancer, which is likely to be a biomarker of EC progression and potential therapeutic target.

Improving the Electron Transport Performance of TiO2 Film by Regulating TiCl4 Post-Treatment for High-Efficiency Carbon-Based Perovskite Solar Cells.

Titanium oxide (TiO2 ) has been widely used as an electron transport layer (ETL) in perovskite solar cells (PSCs). Typically, TiCl4 post-treatment is indispensable for modifying the surfaces of TiO2 ETL to improve the electron transport performance. However, it is challenging to produce the preferred anatase phase-dominated TiO2 by the TiCl4 post-treatment due to the higher thermodynamic stability of the rutile phase. In this work, a mild continuous pH control strategy for effectively regulating the hydrolysis process of TiCl4 post-treatment is proposed. As the weak organic base, urea has been demonstrated can maintain a moderate pH decrease during the hydrolysis process of TiCl4 while keeping the hydrolysis process relatively mild due to the ultra-weak alkalinity. The improved pH environment is beneficial for the formation of anatase TiO2 . Consequently, a uniform anatase-dominated TiO2 surface layer is formed on the mesoporous TiO2 , resulting in reduced defect density and superior band energy level. The interfacial charge recombination is effectively suppressed, and the charge extraction efficiency is improved simultaneously in the fabricated solar cells. The efficiency of the fabricated carbon electrode-based PSCs (C-PSCs) is improved from 16.63% to 18.08%, which is the highest for C-PSCs based on wide-bandgap perovskites.

Positive effects of napping on memory consolidation and resistance against interference.

PURPOSE: This study explored the relationship between naps and memory among habitual nappers in China. METHODS: Medical college students participated and were divided into 30-min, 60-min, and 90-min time-in-bed groups. To evaluate declarative and procedural memory performance, A-B and A-C interfering word pair and interfering finger tapping tasks were employed. RESULTS: Among 60 students, a significant decrease in the correct recall rate in the declarative task after having a nap was found only in the 30-min group (p = 0.005). After learning interference (A-C word pairs), the correct recall rate for the declarative task decreased significantly in all interference tests (ps < 0.001). In the procedural task, the speed of sequence A in the retests increased after having a nap in all three groups (ps < 0.048), with a significant decrease in accuracy only in the 30-min group (p = 0.042). After learning interference (sequence B) in the procedural task, the speed of sequence A increased in the 60-min group after 1 h (p = 0.049), and both the 60-min and 90-min groups showed increased speed after one night (ps < 0.022). No significant improvement in speed was found in the 30-min group (ps > 0.05), and this group showed the lowest accuracy for sequence A (ps < 0.16). CONCLUSION: A habitual nap time-in-bed of 60 or 90 min had better effects on declarative and procedural memory consolidation and better memory resistance against interference in procedural memory.

Insomnia and impacts on facial expression recognition accuracy, intensity and speed: A meta-analysis.

Facial expressions provide nonverbal cues that are important for delivering and interpreting human emotions. Previous studies have shown that the ability to interpret facial emotions correctly could be partially impaired in sleep-deprived people. People with insomnia might also suffer from sleep loss, so we assumed that facial expression recognition ability might also be impaired in people with insomnia. Despite a growing body of research exploring insomnia's potential impacts on facial expression recognition, conflicting results have been reported, and no systematic review of this research body has been conducted. In this study, after screening 1100 records identified through database searches, six articles examining insomnia and facial expression recognition ability were included in a quantitative synthesis. The main outcomes were classification accuracy (ACC), reaction time (RT), and intensity rating-the three most studied facial expression processing variables. Subgroup analysis was performed to identify altered perceptions according to the facial expressions of four emotions-happiness, sadness, fear, and anger-used to examine insomnia and emotion recognition. The pooled standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs) demonstrated that facial expression recognition among people with insomnia was less accurate (SMD = -0.30; 95% CI: -0.46, -0.14) and slower (SMD = 0.67; 95% CI: 0.18, -1.15) compared to good sleepers. The classification ACC of fearful expression was lower in the insomnia group (SMD = -0.66; 95% CI: -1.02, -0.30). This meta-analysis was registered using PROSPERO.

Self-Driven Prenucleation-Induced Perovskite Crystallization Enables Efficient Perovskite Solar Cells.

Perovskite film with high crystal quality is fundamental to achieving high-performance solar cells. A fast nucleation process is crucial to improving the crystallization quality. Here, we propose a self-driven prenucleation strategy to achieve fast nucleation. This is realized through rational solvent design. The key characteristics of different solvents are systematically evaluated. Among them, formamide, with ultra-high dielectric constant, low Gutman donor number, and a high boiling point, is selected as the co-solvent. These unique characteristics render formamide a double-face solvent that is a good solvent for formamidinium iodide (FAI) and CsI while a poor solvent for PbI2 . As a result, formamide induces the self-driven prenucleation of PbI2 -DMSO seeding crystals and accelerates the nucleation, improving the crystalline quality of perovskite film. The efficiency of the hole transport layer-free carbon-based perovskite solar cells is boosted beyond 19 % for the first time.

Correlation between Pancreatic Duct Variation and Related Diseases: An Effective Method Observing the Dual-Energy CT with Low-keV Monoenergetic Images.

PURPOSE: Pancreatic duct variation can affect the secretory function of the pancreas. We aimed to explore the pancreatic duct variation, observed using low-keV monoenergetic images [MEI (+)] of dual-energy CT (DECT), and its relationship with related diseases. We further sought to compare pancreatic duct imaging using low-keV MEI (+) of DECT and magnetic resonance cholangiopancreatography (MRCP). MATERIALS AND METHODS: The DECT and MRCP images of 854 patients were evaluated retrospectively. The 808 patients' pancreatic duct types were classified according to the anatomy and the opening of the pancreatic ducts, and the correlation with related diseases was analyzed. The DECT and MRCP images of 852 patients were graded according to the sharpness of the pancreatic ducts for evaluation. RESULTS: A higher prevalence of acute pancreatitis (AP), chronic pancreatitis (CP), and duodenal papillary carcinoma (DPC) was observed in the variant group. Of the 27 AP cases in the variant group, 9 patients (33.3%) were Type 3c. Additionally, Type 4a was significantly correlated with AP and CP (p < 0.05). Low-keV MEI (+) of DECT outperformed the MRCP images in the sharpness of the pancreatic ducts in 852 patients. CONCLUSIONS: Pancreatic duct variation is associated with AP, CP, and DPC. Low-keV MEI (+) DECT is an effective method to observe the pancreatic duct system.

Elevated serum levels of diamine oxidase, D-lactate and lipopolysaccharides are associated with metabolic-associated fatty liver disease.

BACKGROUND: Studies have suggested an association between metabolic-associated fatty liver disease (MAFLD) and intestinal barrier function. The present study aims to investigate the association between MAFLD and intestinal barrier impairment in humans and identify potential risk factors for MAFLD. METHODS: A total of 491 patients were retrospectively enrolled in this study. The serum levels of diamine oxidase, D-lactate and lipopolysaccharide were measured to evaluate intestinal barrier integrity in patients with and without MAFLD. Binary logistic regression and correlational analyses were conducted to verify the association between MAFLD and serum levels of intestinal barrier biomarkers. RESULTS: We enrolled 294 patients with MAFLD and 197 patients without MAFLD in this study. Patients with MAFLD had higher serum levels of diamine oxidase, D-lactate and lipopolysaccharide (P < 0.001) than those without MAFLD. Multivariate logistic regression analyses showed that BMI [odds ratio (OR) 1.324; P < 0.001], triglycerides (OR 2.649; P = 0.002), nonesterified fatty acids (OR 1.002; P = 0.011), diamine oxidase (OR 1.149; P = 0.011) and D-lactate (OR 1.221; P < 0.001) were independent risk factors for MAFLD. Additionally, serum levels of diamine oxidase and D-lactate increase as liver steatosis became more severe. MAFLD patients with ≥2 metabolic abnormalities had higher serum levels of lipopolysaccharide (P = 0.034). CONCLUSIONS: MAFLD is associated with intestinal barrier impairment. Diamine oxidase and D-lactate are potential predictors of MAFLD, and their serum levels are related to liver steatosis. Intestinal barrier impairment is related to metabolic disorders in patients with MAFLD.

Phenanthroline-based microporous organic materials for removal of Cu(II) from aqueous solution and reutilization of spent adsorbent as catalysts.

Microporous organic polymers (MOPs) possessing large specific surface area with high stability are suitable adsorbent to remove contaminants from water, such as organic pollutant and heavy metal contaminants. Herein, a phenanthroline-based microporous organic polymer (Phen-MOP) has been synthesized through the coupling between benzene and 1,10-phenanthroline. The adsorption kinetics and thermodynamics were investigated. This Phen-MOP exhibited good adsorption efficiency for removal of Cu(II) from water with high structural stability and reusability. The maximum removal efficiency could reach to 98.47% at a Cu(II) concentration of 20 mg/L, pH = 7, 25 °C. It was found by investigating the adsorption isotherms that the maximum adsorption capacity Qm was 128.53 mg/g. Interestingly, after the adsorption of Cu(II), the resulting Phen-MOP-Cu can serve as an efficient heterogeneous catalyst for the Ullmann-type reaction. The structure and composition of the Phen-MOP-Cu were characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). The results indicated that this catalyst possessed immense specific surface area, large pore volume and high stability. The catalyst was easily recyclable and did not significantly lose catalytic activity after being reused six times.

Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma.

Background: Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential stemness-associated biomarker in hepatocellular carcinoma (HCC). Methods: The data of HCC patients from The Cancer Genome Atlas (TCGA) were collected and divided based on the mRNA expression-based stemness index (mRNAsi) in this study. Weighted gene coexpression network analysis (WGCNA) and the protein-protein interaction (PPI) network were performed, and the genes were screened through the Cytoscape software. Then, we constructed a prognostic expression signature using the multivariable Cox analysis and verified using the GEO and ICGC databases. Even more importantly, we used the three-dimensional (3D) fibrin gel to enrich the tumor-repopulating cells (TRCs) to validate the expression of the signature in CSCs by quantitative RT-PCR. Results: mRNAsi was significantly elevated in tumor and high-mRNAsi score was associated with poor overall survival in HCC. The positive stemness-associated (blue) module with 737 genes were screened based on WGCNA, and Budding uninhibited by benzimidazoles 1 (BUB1) was identified as the hub gene highly related to stemness in HCC. Then, the prognostic value and stemness characteristics were well validated in the ICGC and GSE14520 cohorts. Further analysis showed the expression of BUB1 was elevated in TRCs. Conclusion: BUB1, as a potential stemness-associated biomarker, could serve as a therapeutic CSCs-target and predicted the clinical outcomes of patients with HCC.

Structural Model of Napping Motivation Among Chinese College Students Based on Self-Rating: Evidence from an Exploratory Factor Analysis.

Purpose: Previous epidemiological and psychological studies have assessed the effects of napping on individual performance and health. However, these studies did not distinguish between spontaneous and passive napping due to sleep disorders. Therefore, this study aimed to explore the potential motivation for napping among Chinese college students and to assess the relationship between different nap motivations and sleep. Patients and Methods: This cross-sectional study was conducted at a university in Shanghai in March 2021 using convenience sampling. A total of 564 Chinese college students with self-reported napping habits participated in this study. Exploratory factor analysis (EFA) was employed to analyze 34 self-rated motivations for napping to derive a potential structural model of napping motivation. Correlation and multiple linear regression analyses were performed to determine the influence of nap motivation on sleep behavior. Results: Chinese college students mainly take naps to reduce fatigue, usually in the form of frequent and long naps (6.25 ± 1.24 days; 64.62 ± 23.70 min). A structural model of nap motivation named the I-DREAM model was proposed, consisting of six factors: restorative, induced, mindful, appetitive, dysregulative, and exercise naps. There were also sex differences in nap motivation, as women preferred restorative naps and appetitive naps, while men preferred exercise naps (p < 0.01, p < 0.05). Furthermore, there was a significant correlation between nap motivation on nap duration, frequency and nighttime sleep quality (R2 = 2.70-18.9%). Conclusion: The proposed I-DREAM model implies that there are population differences in napping motivation. Different motivations also have different relationships with napping patterns and nighttime sleep. In understanding the relationship between naps and health status, nap motivation may be an extremely important influencing factor.

Planning Ability and Alertness After Nap Deprivation: Beneficial Effects of Acute Moderate-Intensity Aerobic Exercise Greater Than Sitting Naps.

Nap deprivation is regarded as a sleep loss for habitual nappers. The beneficial effects of napping and moderate-intensity aerobic exercise on the reduction in planning ability following nighttime sleep deprivation have been proven. However, it is still unknown whether it can improve the performance decline caused by daytime nap deprivation in habitual nappers. Seventy-four healthy adults who had a long-term habit of taking naps were assigned to three interventions after receiving nap deprivation: (1) Control group (no intervention); (2) Nap group (15-min sitting naps); (3) Exercise group (15-min aerobic exercise), in which subjective alertness, mood, fatigue, and task performance in objective alertness (Psychomotor Vigilance Task, PVT) and planning ability (the Tower of London Task) were measured. Results showed that nap deprivation negatively influenced some performance on the psychomotor vigilance (i.e., response times and 10% slowest response time) and planning ability (i.e., planning time). And acute moderate-intensity aerobic exercise improved psychomotor alertness (i.e., response times) and planning ability (i.e., execution accuracy, execution time), a 15-min sitting naps only alleviated subjective fatigue, whereas some performance (i.e., response times) deteriorated when no intervention was used. These findings suggested that acute moderate-intensity aerobic exercise has a better restorative effect on the reduced planning ability and objective alertness due to nap deprivation compared to sitting naps.

Education and subjective well-being in Chinese rural population: A multi-group structural equation model.

PURPOSES: This study aimed to explore the effect of education on subjective well-being (SWB) of Chinese rural dwellers who just shook off poverty in 2019 and to investigate the mediating role of social support and moderating role of age on the association. METHODS: Social support rating scale (SSRS) and General Well-Being Schedule (GWBS) were administrated among 1094 Chinese rural dwellers from Anqing, Anhui Province, China. Structural equation modeling (SEM) and multi-group SEM were performed to examine the mediating role of social support and moderating role of age in the link between education and SWB, respectively. RESULTS: The findings indicated that social support fully mediated the relationship between education and SWB in rural residents. Age moderated the indirect relationship between education and SWB (first stage moderation model) such that the effect of education on social support would be strengthened with aging process. CONCLUSIONS: The results add to our understanding of the protective role of education in SWB among Chinese rural dwellers, and shed new light on the potential mechanisms underlying the association between education and SWB with respect to the mediating role of social support and moderating role of age.

DNMT3A facilitates colorectal cancer progression via regulating DAB2IP mediated MEK/ERK activation.

The inactivation of tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) by epigenetic and post-transcriptional modification has been reported in multiple human malignancies. DNA methyltransferase 3A (DNMT3A) is involved in de novo establishment of DNA methylation and plays a vital role in tumorigenesis. However, whether DNMT3A can regulate colorectal cancer (CRC) progression via modulation of DAB2IP remains unclear. In this study, we revealed that DNMT3A was significantly increased in CRC, predicting a poor overall survival. Functionally, ectopic expression of DNMT3A in CRC cells enhanced cell proliferation, whereas DNMT3A knockdown had the opposite effect by inducing cell cycle arrest. Mechanistically, methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) proved that the expression of DAB2IP was epigenetically suppressed by DNMT3A-mediated promoter methylation in CRC cells. Using dual-luciferase reporter assay and ChIP-PCR assay, we further confirmed that DNMT3A restrained the transcriptional activity of DAB2IP promoter through directly binging to it. In addition, DNMT3A could activate the MEK/ERK signaling pathway via efficiently downregulating DAB2IP. Inhibition of the MEK/ERK cascade abrogated the oncogenic effects of DNMT3A on CRC cells. In conclusion, our study demonstrates that DNMT3A facilitates CRC progression by regulating DAB2IP mediated MEK/ERK activation, providing promising targets for CRC treatment.

DOC-2/DAB2 interactive protein destabilizes c-Myc to impair the growth and self-renewal of colon tumor-repopulating cells.

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) suppressed c-Myc expression to inhibit TRC expansion and self-renewal. Particularly, DAB2IP disrupted c-Myc stability through glycogen synthase kinase 3ß/protein phosphatase 2A-B56α-mediated phosphorylation and dephosphorylation cascade on c-Myc protein, leading to its eventual degradation through the ubiquitin-proteasome pathway. The expression of DAB2IP was negatively correlated with c-Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self-renewal.