Disruption of SLFN11 Deficiency-Induced CCL2 Signaling and Macrophage M2 Polarization Potentiates Anti-PD-1 Therapy Efficacy in Hepatocellular Carcinoma.

BACKGROUND & AIMS: The therapeutic effect of immune checkpoint inhibitors (ICIs) is poor in hepatocellular carcinoma (HCC) and varies greatly among individuals. Schlafen (SLFN) family members have important functions in immunity and oncology, but their roles in cancer immunobiology remain unclear. We aimed to investigate the role of the SLFN family in immune responses against HCC. METHODS: Transcriptome analysis was performed in human HCC tissues with or without response to ICIs. A humanized orthotopic HCC mouse model and a co-culture system were constructed, and cytometry by time-of-flight technology was used to explore the function and mechanism of SLFN11 in the immune context of HCC. RESULTS: SLFN11 was significantly up-regulated in tumors that responded to ICIs. Tumor-specific SLFN11 deficiency increased the infiltration of immunosuppressive macrophages and aggravated HCC progression. HCC cells with SLFN11 knockdown promoted macrophage migration and M2-like polarization in a C-C motif chemokine ligand 2-dependent manner, which in turn elevated their own PD-L1 expression by activating the nuclear factor-κB pathway. Mechanistically, SLFN11 suppressed the Notch pathway and C-C motif chemokine ligand 2 transcription by binding competitively with tripartite motif containing 21 to the RNA recognition motif 2 domain of RBM10, thereby inhibiting tripartite motif containing 21-mediated RBM10 degradation to stabilize RBM10 and promote NUMB exon 9 skipping. Pharmacologic antagonism of C-C motif chemokine receptor 2 potentiated the antitumor effect of anti-PD-1 in humanized mice bearing SLFN11 knockdown tumors. ICIs were more effective in patients with HCC with high serum SLFN11 levels. CONCLUSIONS: SLFN11 serves as a critical regulator of microenvironmental immune properties and an effective predictive biomarker of ICIs response in HCC. Blockade of C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 signaling sensitized SLFN11low HCC patients to ICI treatment.

Chemokine CCL21 determines immunotherapy response in hepatocellular carcinoma by affecting neutrophil polarization.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) is poor and great heterogeneity among individuals. Chemokines are highly correlated with tumor immune response. Here, we aimed to identify an effective chemokine for predicting the efficacy of immunotherapy in HCC. METHODS: Chemokine C-C motif ligand 21 (CCL21) was screened by transcriptomic analysis in tumor tissues from HCC patients with different responses to ICIs. The least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive nomogram. Neutrophils in vitro and HCC subcutaneous tumor model in vivo were applied to explore the role of CCL21 on the tumor microenvironment (TME) of HCC. RESULTS: Transcriptome analysis showed that CCL21 level was much higher in HCC patients with response to immunotherapy. The predictive nomogram was constructed and validated as a classifier. CCL21 could inhibit N2 neutrophil polarization by suppressing the activation of nuclear factor kappa B (NF-κB) pathway. In addition, CCL21 enhanced the therapeutic efficacy of ICIs. CONCLUSION: CCL21 may serve as a predictive biomarker for immunotherapy response in HCC patients. High levels of CCL21 in TME inhibit immunosuppressive polarization of neutrophils. CCL21 in combination with ICIs may offer a novel therapeutic strategy for HCC.

2†µm sub-GHz harmonic mode-locked soliton generation based on a Bi2S3 saturable absorber.

Saturable absorber (SA) based harmonic mode-locking (HML) techniques at 2 µm waveband are much less reported than those at 1.5 µm waveband, the maximum repetition rate of the harmonic pulse generated by such techniques at 2 µm waveband is also much lower than those generated at 1.5 µm waveband. In this paper, the 39th harmonic with the repetition rate of 908.6 MHz is realized in a Bi2S3-based thulium-doped fiber laser. The fundamental mode-locked pulse has a central wavelength of 1954.2 nm and a 3-dB bandwidth of 5.1 nm. The repetition rate is 23.27 MHz and the pulse width is 902 fs. The characteristics of the material and harmonic mode-locked pulse are investigated. To the best of our knowledge, this is the highest and the closest resonance frequency to GHz among the reported SA-based harmonic mode-locked fiber lasers operating at 2 µm waveband.

Restrictive Regulation of Ionic Liquid Quaternary Ammonium Salt in SBA-15 Pore Channel for Efficient Carbon Dioxide Conversion.

Herein, the synthesis of a new type of catalyst, SBA-M (Schiff complex of different metal types grafted on SBA-15) based on a quaternization reaction, is described. Various amounts of ionic liquid were grafted into the pore channels of SBA-15 using the post-grafting method, which allowed the ionic liquid to be grafted into the pore channels restrictively. Notably, over six cycles, SBA-Mn (0.2) has been shown to maintain its catalytic activity and stability. In addition, a reaction mechanism for the cycloaddition of CO2 with epoxides based on density-functional theory is proposed. The cycloaddition reaction of CO2 and epoxides is an efficient way of carbon fixation. It is demonstrated that the metal coordinated with the oxygen atom of the epoxides and that a halogen attacked the carbon of epoxides. Moreover, theoretical calculations and synthesis strategy provide a new approach for CO2 conversion.

Study of the Cycloaddition of CO2 with Styrene Oxide Over Six-Connected spn Topology MOFs (Zr, Hf) at Room Temperature.

A series of MOFs with a 6-connected spn topology were synthesized (MOF-808-(Zr, Hf), PCN-777-(Zr, Hf), MOF-818-(Zr, Hf)). Through the in situ DRIFTS of NH3 adsorption-desorption, we found that the activated catalyst mainly contains Lewis acid sites. The effects of different organic ligands on the Lewis acid of the Zr6 cluster were analyzed by XPS and NH3 -TPD, and the relative Lewis acidity of the same metal was obtained: PCN-777>MOF-808>MOF-818. In the Py-FTIR results, we confirmed that MOF-818 has a higher acid site density. In the activity test, MOFs with mesoporous structure showed better catalytic activity under normal temperature and pressure. Among them, MOF-818 can still maintain a high degree of crystallinity after catalysis. Finally, we use density functional theory to propose the mechanism of the cycloaddition reaction of carbon dioxide and styrene oxide. The results show that the metal is coordinated with styrene oxide and halogens attack the ß carbon of the epoxide.

Lack of association of microvessel density with prognosis of renal cell carcinoma: evidence from meta-analysis.

To investigate microvessel density (MVD) and its association with prognosis of renal cell carcinoma (RCC) by means of a meta-analysis. We obtained published studies and extracted appropriate data, then did a meta-analysis to estimate the predictive role of MVD by combining estimated effect-size from individual studies. Analyses for overall survival (OS) and cancer-specific survival (CSS) were performed, separately. Subgroup analysis stratified by biomarkers were also performed for studies using CD34, factor VIII-related antigen (F VIII) and others, respectively. A total of 20 studies were included for meta-analyses including nine (four for F VIII, three for CD34, and two for others) for OS and 11 (two for F VIII, seven for CD34 and two for others) for CSS. There was no significance of MVD predicting OS or CSS of RCC. The pooled HR for OS was 0.910 (95% CI 0.824-1.006; P = 0.065) and CSS was 0.977 (95% CI: 0.915-1.043; P = 0.487). We failed to observe significant association between MVD and prognosis of RCC. Additional studies are needed to provide more precise evidences to support our results.

Effect of Orthodontic Treatment on the Outcomes of Endodontically Treated Teeth: A Cone-Beam Computed Tomography Analysis.

INTRODUCTION: Often there is the need of moving endodontically treated teeth. Orthodontic movement may have no effect on the prognosis of teeth with root canal treatment (RCT). To verify this subject, we evaluated the effect of orthodontic movement on the prognosis of RCT teeth using cone-beam computed tomography (CBCT) and further explored the influence of orthodontic movement on the prognosis of RCT teeth with and without apical periodontitis (AP). METHODS: This retrospective study was conducted by evaluating 169 RCT teeth of 100 patients who had undergone fixed orthodontic treatment. AP was assessed and classified using the CBCT periapical index. Univariate analysis of RCT outcome was performed for the total RCT group, RCT without AP group and RCT with AP group. Multivariate logistic regression was performed for the total RCT group and RCT without AP group, respectively, but not for the RCT with AP group. Variables related to the prognosis of RCT were included, such as age, gender, tooth position, RCT quality, coronal restoration quality, periodontal condition, orthodontic traction distance, and orthodontic rotation angle. RESULTS: The orthodontic traction distance and rotation angle were not significantly correlated to the RCT outcomes, regardless of the presence of AP. Among the total RCT group, teeth with unqualified RCT (odds ratio = 3.42, P = .004) and inadequate coronal restoration (odds ratio = 4.40, P = .031) had a lower success rate. Of the 97 RCT teeth without AP, unqualified RCT was a risk factor for treatment failure (odds ratio = 3.55, P = .041). Of the 72 RCT teeth with AP, the univariate analysis showed that RCT quality were significantly related to the outcome (P = .042). CONCLUSIONS: Orthodontic movement had no effect on the prognosis of RCT teeth regardless of the presence of AP.

Repolarization of Immunosuppressive Macrophages by Targeting SLAMF7-Regulated CCL2 Signaling Sensitizes Hepatocellular Carcinoma to Immunotherapy.

Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various immune functions, we investigated the role of specific SLAM receptors in the immunobiology of HCC. Comparison of the transcriptomic landscapes of immunotherapy-responsive and nonresponsive patients with advanced HCC identified SLAMF7 upregulation in immunotherapy-responsive HCC, and patients with HCC who responded to immunotherapy also displayed higher serum levels of SLAMF7. Loss of Slamf7 in liver-specific knockout mice led to increased hepatocarcinogenesis and metastasis, elevated immunosuppressive macrophage infiltration, and upregulated PD-1 expression in CD8+ T cells. HCC cell-intrinsic SLAMF7 suppressed MAPK/ATF2-mediated CCL2 expression to regulate macrophage migration and polarization in vitro. Mechanistically, SLAMF7 associated with SH2 domain-containing adaptor protein B (SHB) through its cytoplasmic 304 tyrosine site to facilitate the recruitment of SHIP1 to SLAMF7 and inhibit the ubiquitination of TRAF6, thereby attenuating MAPK pathway activation and CCL2 transcription. Pharmacological antagonism of the CCL2/CCR2 axis potentiated the therapeutic effect of anti-PD-1 antibody in orthotopic HCC mouse models with low SLAMF7 expression. In conclusion, this study highlights SLAMF7 as a regulator of macrophage function and a potential predictive biomarker of immunotherapy response in HCC. Strategies targeting CCL2 signaling to induce macrophage repolarization in HCC with low SLAMF7 might enhance the efficacy of immunotherapy. SIGNIFICANCE: CCL2 upregulation caused by SLAMF7 deficiency in hepatocellular carcinoma cells induces immunosuppressive macrophage polarization and confers resistance to immune checkpoint blockade, providing potential biomarkers and targets to improve immunotherapy response in patients.

Arsenic distribution and adsorption behavior in the sediments of the Daliao River System in China.

This study investigated the arsenic (As) distribution and adsorption behavior in sediments of the Daliao River System (DRS). Results indicated that the total As was 2.6-83.1 mg kg(-1) in the sediments of the DRS. The pseudo-first order model and intra-particle diffusion model give a good fit of the experimental kinetics data for As, indicating that particle diffusion mechanism may not be the rate controlling step while this mechanism is involved. By comparing the zero equilibrium As concentration (EAsCo) with the actual As concentration in the overlying water of the DRS, all the sediments showed a trend of releasing As. Arsenic exhibited strong adsorption on sediment at pH 4.5-7. Arsenic retention by sediment was much enhanced by Ca2+ compared to Na+. More As was desorbed by phosphate at low and high pH extremes. The added or sorbed As was mainly transferred to the specifically sorbed fraction and amorphous Fe (Al) oxyhydroxides bound fraction, indicating Fe oxides are a major sorbent of As in sediment.

Geochemical baseline level and function and contamination of phosphorus in Liao River Watershed sediments of China.

The quantitative assessment of P contamination in sediments is a challenge due to sediment heterogeneity and the lacking of geochemical background or baseline levels. In this study, a procedure was proposed to determine the average P background level and P geochemical baseline level (GBL) and develop P geochemical baseline functions (GBF) for riverbed sediments of the Liao River Watershed (LRW). The LRW has two river systems - the Liao River System (LRS) and the Daliao River System (DRS). Eighty-eight samples were collected and analyzed for P, Al, Fe, Ca, organic matter, pH, and texture. The results show that Fe can be used as a better particle-size proxy to construct the GBF of P (P (mg/kg) = 39.98 + 166.19 × Fe (%), R(2) = 0.835, n = 66). The GBL of P was 675 mg/kg, while the average background level of P was 355 mg/kg. Noting that many large cities are located in the DRS watershed, most of the contaminated sites were located within the DRS and the riverbed sediments were more contaminated by P in the DRS watershed than in the LRS watershed. The geochemical background and baseline information of P are of great importance in managing P levels within the LRW.

Contamination and ecological risk assessment of toxic trace elements in the Xi River, an urban river of Shenyang city, China.

The objectives of this study were to assess the enrichment, contamination, and ecological risk posed by toxic trace elements in the sediments of the Xi River in the industrialized city of Shenyang, China. Surface sediment and sediment core were collected; analyzed for toxic trace elements; and assessed with an index of geoaccumulation (Igeo), enrichment factor (EF) value, potential ecological risk factor (Er), ecological risk index (RI), and probable effect concentration quotient (PECQ). Elemental concentrations (milligram per kilogram) were 8.5-637.9 for As, 6.5-103.9 for Cd, 12.2-21.9 for Co, 90.6-516.0 for Cr, 258.1-1,791.5 for Cu, 2.6-19.0 for Hg, 70.5-174.5 for Ni, 126.9-1,405.8 for Pb, 3.7-260.0 for Sb, 38.4-100.4 for V, and 503-4,929 for Zn. The Igeo, EF, Er, and PECQ indices showed that the contamination of Cd and Hg was more serious than that of As, Cr, Cu, Ni, Pb, Sb, and Zn, whereas the presence of Co and V might be primarily from natural sources. The Igeo index for Cr and Ni might underestimate the degree of contamination, potentially as a result of high concentrations of these elements in the shale. The RI index was higher than 600, indicating a notably high ecological risk of sediment for the river. The average PECQ for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn ranged from 1.4 to 4.1 for surface sediment and from 5.2 to 9.6 in the sediment cores, indicating a high potential for an adverse biological effect. It was concluded that the sediment in the Xi River was severely contaminated and should be remediated as a hazardous material.

Analysis of the mixed teaching of college physical education based on the health big data and blockchain technology.

In the era of health big data, with the continuous development of information technology, students' physical health management also relies more on various information technologies. Blockchain, as an emerging technology in recent years, has the characteristics of high efficiency and intelligence. College physical education is an important part of college students' health big data. Unlike cultural classes, physical education with its rich movements and activities, leaves teachers no time to monitor students' real classroom performance. Therefore, we propose a human pose estimation method based on cross-attention-based Transformer multi-scale representation learning to monitor students' class concentration. Firstly, the feature maps with different resolution are obtained by deep convolutional network and these feature maps are transformed into multi-scale visual markers. Secondly, we propose a cross-attention module with the multi-scales. The module reduces the redundancy of key point markers and the number of cross fusion operations through multiple interactions between feature markers with different resolutions and the strategy of moving key points for key point markers. Finally, the cross-attention fusion module extracts feature information of different scales from feature tags to form key tags. We can confirm the performance of the cross-attention module and the fusion module by the experimental results conducting on MSCOCO datasets, which can effectively promote the Transformer encoder to learn the association relationship between key points. Compared with the completive TokenPose method, our method can reduce the computational cost by 11.8% without reducing the performance.

Correction: Highly photoluminescent nitrogen-rich carbon dots from melamine and citric acid for the selective detection of iron(iii) ion.

[This corrects the article DOI: 10.1039/C5RA26521E.].

Association between odontogenic conditions and maxillary sinus abnormalities: a retrospective cone-beam computed-tomographic study.

BACKGROUND: In this study, we investigated the correlation between odontogenic conditions and the presence of maxillary sinus (MS) abnormalities using cone-beam computed tomography (CBCT) imaging. METHODS: The study unit was defined as the ipsilateral MS, maxillary alveolar bone, and posterior teeth. The study included 1,140 study units from 570 patients visualized with CBCT. MS abnormalities, MS septal walls, the anatomical relationship between the MS and the teeth, and missing teeth were recorded. Adjacent odontogenic infections, including periapical lesions, periodontal bone loss, and combined periodontal-endodontic lesions, were documented, and the shortest distance between the infection and the MS floor was measured. The possible correlations between odontogenic conditions and MS abnormalities were analyzed. Whether the anatomical relationship between the MS and the teeth was related to age or sex was analyzed. The chi-squared test, Fisher's exact test, Mann-Whitney U test, Kruskal-Wallis H test, and logistic regression were used for the statistical analyses. RESULTS: MS abnormalities were detected in 57.54% of patients and 42.89% of MSs. Male sex (OR =1.653; P<0.001) and a MS adjacent to teeth with periapical lesions (OR =5.771; P<0.001), periodontal bone loss (OR =2.778; P<0.001), or combined periodontal-endodontic lesions (OR =13.818; P<0.001) increased the probability of MS abnormalities. In MSs with a single infected tooth, male sex (OR =2.413; P=0.045), infected molar (OR =3.431; P=0.008), and a smaller distance between the infection and the MS floor (OR =0.871; P=0.021) increased the probability of MS abnormality. The maxillary root apices of older subjects tended to be farther from the MS (P<0.001). CONCLUSIONS: Adjacent odontogenic infection increased the probability of MS abnormalities. The likelihood of MS abnormality was related to the distance between the infection and the MS, not to the type of infection.

Efficacy of hemoporfin-PDT on port-wine stains: A retrospective analysis of 2952 cases.

OBJECTIVE: To conduct a retrospective analysis of Hemoporfin photodynamic therapy (HMME-PDT) in the treatment of port-wine stains (PWS). METHOD: A retrospective analysis was conducted based on the clinical data from March 2017 to December 2022, so as to summarize the demographic characteristics, clinical efficacy and adverse reactions. The effectiveness of HMME-PDT was examined with respect to treatment times, age, gender, subtype, and location of PWS lesions. RESULT: The age of the 2952 cases ranged from 8 months to 56 years old (median, 2.8 years), with 1419 males (48.07 %), and 1533 females (51.93 %). There were 669 cases of pink type (22.66 %), 2184 cases of purplish red type (73.98 %), and 99 cases of nodular thickening type (3.35 %). The prevalence location was face (88.04 %), neck (14.94 %), limbs and trunk. 1602 cases (54.27 %) had never received treatment, 661 cases (22.39 %) had been treated by pulse dye laser (PDL), 229 cases (7.76 %) had previously been treated by PDT, 296 cases (10.03 %) had received both the modalities. The 2952 cases completed totally 7996 HMME-PDT times. Cure rate and effective rate increased continuously with the number of treatments. The pink type has the highest cure rate and effective rate, followed by the purplish red type and the last was the nodular thickening type. The therapeutic effects are considerably influenced by age, subtype, and treatment site (P < 0.05). However, there was no significant difference in the effectiveness of HMME-PDT between both genders. The local adverse reactions after the first treatment included edema (97.73 %), itching (82.62 %), purpura-like change (79.51 %), crusts (24.59 %), infection (4.07 %), scars (1.08 %), hyperpigmentation (0.61 %), and depigmentation (0.41 %). Nausea and vomiting occurred in 2 juveniles and 1 young adult (5, 6 and 22 years old respectively) immediately after treatment, and did not interfere with the administration of the treatment. Patients aged 21-30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia compared to those aged 15 or younger. There was no distinct systemic adverse reaction, such as allergic responses, cardiovascular effects, neurological symptoms, hematological abnormalities, respiratory symptoms, or musculoskeletal issues. CONCLUSION: HMME-PDT is preferred in treating PWS, with relatively high effective rate and cure rate, mild local reactions and no distinct systemic adverse reaction.

Intratumoral PPT1-positive macrophages determine immunosuppressive contexture and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy with limited treatment options and poor prognosis. Macrophages are enriched in the HCC microenvironment and have a significant impact on disease progression and therapy efficacy. We aim to identify critical macrophages subsets involved in HCC development. METHODS: Macrophage-specific marker genes were identified through single-cell RNA sequencing analyses. The clinical significance of macrophages with palmitoyl-protein thioesterase 1 (PPT1) positive was investigated in 169 patients with HCC from Zhongshan Hospital using immunohistochemistry and immunofluorescence. The immune microenvironment of HCC and the functional phenotype of PPT1+ macrophages were explored using cytometry by time-of-flight (CyTOF) and RNA sequencing. RESULTS: Single-cell RNA sequencing analyses revealed that PPT1 was predominantly expressed in macrophages in HCC. Intratumoral PPT1+ macrophages abundance was associated with inferior survival durations of patients and an independent risk factor of prognosis for HCC. High throughput analyses of immune infiltrates showed that PPT1+ macrophage-enriched HCCs were characterized by high infiltration of CD8+ T cells with increased programmed death-1 (PD-1) expression. PPT1+ macrophages exhibited higher galectin-9, CD172a, and CCR2 levels but lower CD80 and CCR7 levels than PPT1- macrophages. Pharmacological inhibition of PPT1 by DC661 suppressed mitogen-activated protein kinase (MAPK) pathway activity but activated nuclear factor kappa B (NF-κB) pathway in macrophages. In addition, DC661 enhanced the therapeutic efficacy of anti-PD-1 antibody in the HCC mouse model. CONCLUSIONS: PPT1 is mainly expressed in macrophages in HCC and promotes immunosuppressive transformation of macrophages and tumor microenvironment. PPT1+ macrophage infiltration is associated with poor prognosis of patients with HCC. Targeting PPT1 may potentiate the efficacy of immunotherapy for HCC.

Functions of Key Enzymes of Glycolytic Metabolism in Tumor Microenvironment.

The tumor microenvironment (TME) plays a crucial role in tumor initiation, growth and metastasis. Metabolic enzymes involved in tumor glycolytic reprogramming, including hexokinase, pyruvate kinase, and lactate dehydrogenase, not only play key roles in tumorigenesis and maintaining tumor cell survival, but also take part in the modulation of the TME. Many studies have been devoted to the role of key glycolytic enzymes in the TME over the past decades. We summarize the studies on the role of glycolytic enzymes in the TME of these years and found that glycolytic enzymes remodel the TME primarily through regulating immune escape, angiogenesis, and affecting stromal cells and exosomes. Notably, abnormal tumor vascular system, peritumoral stromal cells, and tumor immunosuppressive microenvironment are important contributors to the failure of antitumor therapy. Therefore, we discuss the mechanisms of regulation by key glycolytic enzymes that may contribute to a promising biomarker for therapeutic intervention. We argue that targeting key glycolytic enzymes in combination with antiprogrammed cell death ligand 1 or antivascular endothelial growth factor could emerge as the more integrated and comprehensive antitumor treatment strategy.

Whole-exome sequencing reveals the metastatic potential of hepatocellular carcinoma from the perspective of tumor and circulating tumor DNA.

BACKGROUND: Relapse of hepatocellular carcinoma (HCC) due to vascular invasion is common, but the genomic mechanisms remain unclear, and molecular determinants of high-risk relapse cases are lacking. We aimed to reveal the evolutionary trajectory of microvascular invasion (MVI) and develop a predictive signature for relapse in HCC. METHODS: Whole-exome sequencing was performed on tumor and peritumor tissues, portal vein tumor thrombus (PVTT), and circulating tumor DNA (ctDNA) to compare the genomic profiles between 5 HCC patients with MVI and 5 patients without MVI. We conducted an integrated analysis of exome and transcriptome to develop and validate a prognostic signature in two public cohorts and one cohort from Zhongshan Hospital, Fudan University. RESULTS: Shared genomic landscapes and identical clonal origins among tumor, PVTT, and ctDNA were observed in MVI ( +) HCC, suggesting that genomic changes favoring metastasis occur at the primary tumor stage and are inherited in metastatic lesions and ctDNA. There was no clonal relatedness between the primary tumor and ctDNA in MVI ( - ) HCC. HCC had dynamic mutation alterations during MVI and exhibited genetic heterogeneity between primary and metastatic tumors, which can be comprehensively reflected by ctDNA. A relapse-related gene signature named RGSHCC was developed based on the significantly mutated genes associated with MVI and shown to be a robust classifier of HCC relapse. CONCLUSIONS: We characterized the genomic alterations during HCC vascular invasion and revealed a previously undescribed evolution pattern of ctDNA in HCC. A novel multiomics-based signature was developed to identify high-risk relapse populations.

[Corrigendum] miR­647 and miR­1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the scratch­wound assays shown in Fig. 3A on p. 8195, the data shown for the '0 h/NC' and '0 h/miR­1914 antagomir' data panels appeared to be strikingly similar, such that they may have been derived from the same original source. The authors have consulted their original data, and realize that the '0 h/miR­1914 antagomir' data panel was inadvertently selected incorrectly for Fig. 3A. The corrected version of Fig. 3, now showing the correct data for the '0 h/miR­1914 antagomir' data panel in Fig. 3A, is shown on the next page. Note that the errors in Fig. 3 did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16, 8189­8199, 2017; DOI: 10.3892/mmr.2017.7675].