Early detection and stratification of colorectal cancer using plasma cell-free DNA fragmentomic profiling.

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.

Identification and validation of cuproptosis and disulfidptosis related genes in colorectal cancer.

Colorectal cancer, the third most prevalent malignant cancer, is associated with poor prognosis. Recent studies have investigated the mechanisms underlying cuproptosis and disulfidptosis in colorectal cancer. However, whether genes linked to these processes impact the prognosis of colorectal cancer patients through analogous mechanisms remains unclear. In this study, we developed a model of cuproptosis and disulfidptosis in colorectal cancer and concurrently explored the role of the pivotal model gene HSPA8 in colorectal cancer cell lines. Our results revealed a positive correlation between cuproptosis and disulfidptosis, both of which are emerging as protective factors for the prognosis of CRC patients. Consequently, a prognostic model encompassing HSPA8, PDCL3, CBX3, ATP6V1G1, TAF1D, RPL4, and RPL14 was constructed. Notably, the key gene in our model, HSPA8, exhibited heightened expression and was validated as a protective prognostic factor in colorectal cancer, exerting inhibitory effects on colorectal cancer cell proliferation. This study offers novel insights into the interplay between cuproptosis and disulfidptosis. The application of the prognostic model holds promise for more effectively predicting the overall survival of colorectal cancer patients.

Circ_MAPK9 promotes STAT3 and LDHA expression by silencing miR-642b-3p and affects the progression of hepatocellular carcinoma.

BACKGROUND: Aberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC). METHODS: Circ_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation. RESULTS: The expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression. CONCLUSIONS: Circ_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.

[Multiresolution discrete optimization registration method of ultrasound and magnetic resonance images based on key points].

The registration of preoperative magnetic resonance (MR) images and intraoperative ultrasound (US) images is very important in the planning of brain tumor surgery and during surgery. Considering that the two-modality images have different intensity range and resolution, and the US images are degraded by lots of speckle noises, a self-similarity context (SSC) descriptor based on local neighborhood information was adopted to define the similarity measure. The ultrasound images were considered as the reference, the corners were extracted as the key points using three-dimensional differential operators, and the dense displacement sampling discrete optimization algorithm was adopted for registration. The whole registration process was divided into two stages including the affine registration and the elastic registration. In the affine registration stage, the image was decomposed using multi-resolution scheme, and in the elastic registration stage, the displacement vectors of key points were regularized using the minimum convolution and mean field reasoning strategies. The registration experiment was performed on the preoperative MR images and intraoperative US images of 22 patients. The overall error after affine registration was (1.57 ± 0.30) mm, and the average computation time of each pair of images was only 1.36 s; while the overall error after elastic registration was further reduced to (1.40 ± 0.28) mm, and the average registration time was 1.53 s. The experimental results show that the proposed method has prominent registration accuracy and high computational efficiency.

Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma.

OBJECTIVE: This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function. METHODS: Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection. RESULTS: Forty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis. CONCLUSION: The established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy.

Polystyrene microplastics aggravate acute pancreatitis in mice.

Microplastics (MPs) with a diameter of < 5 mm are emerging as a new type of environmental pollutants. With the discovery of MPs in human tissues, the health risks of MPs have attracted considerable attention in recent years. In this study, we aimed to investigate the impact of MPs on acute pancreatitis (AP). We exposed male mice to 100 and 1000 µg/L polystyrene MPs for 28 days, then intraperitoneally injected mice with cerulein to develop acute pancreatitis (AP). The results demonstrated that MPs dose-dependently exacerbated pancreatic injuries and inflammation in AP. High-dose MPs significantly increased intestinal barrier disruption in AP mice, which may be partly responsible for the aggravation of AP. Moreover, through tandem mass tag (TMT)- based proteomics of pancreatic tissues, we screened 101 differentially expressed proteins (DEPs) between AP mice and high-dose MPs-treated AP mice. Gene Ontology and KEGG Pathway analysis revealed that the DEPs were mainly implicated in the molecular events including cytoskeleton organization, acute inflammatory response, arginine metabolism, etc. These mechanisms may also contribute to the aggravating AP effects of MPs. Collectively, our data provide new evidence for the harmful potential of MPs.

[Success rate of one-stop procedure for atrial fibrillation ablation and its impact on cardiac function: a propensity-matched study].

OBJECTIVE: To investigate the effect of the combination of atrial fibrillation (AF) ablation and left atrial appendage closure (LAAC) on cardiac function and the success rate of AF ablation. METHODS: We retrospectively analyzed the data of 56 patients with AF undergoing a one-stop procedure for AF ablation and LAAC in our hospital between May, 2015 and May, 2019. Propensity score matching (PSM) at the ratio of 1:1 was used to select 56 control patients undergoing AF ablation at high risk of stroke, for matching with the hybrid procedure group. The perioperative complications, thromboembolic events, recurrence of atrial arrhythmia and cardiac function were compared between the groups. RESULTS: The two groups of patients were comparable for age, gender, BMI, duration and type of AF, concomitant diseases, CHA2DS2-VASc and HAS-BLED scores (P > 0.05). The incidence of complications did not differ significantly between the hybrid procedure group and AF ablation group (17.9% vs 12.5%, P=0.430). Compared with the control patients with AF ablation alone, the patients undergoing the hybrid procedure had a lowered incidence of thromboembolic events, but the difference was not statistically significant (1.8%vs 3.6%, P=1.000). The hybrid procedure did not improve the success rate of AF ablation (OR: 1.338, 95%CI: 0.451-3.973, P= 0.600) but significantly improved the cardiac function parameters including NT-pro BNP (945.3±1401.6 pg/mL vs 1520.7±2089.1 pg/mL, P=0.010), LVEF[(60.8±7.0)% vs (58.6±7.8)%, P=0.044], and left atrial diameter (43.9±7.5 mm vs 45.6±6.3 mm, P=0.076); but the improvement of cardiac function was more obvious in the control patients undergoing AF ablation alone (P < 0.039). CONCLUSIONS: The combination of AF ablation and LAAC is safe but does not improve the success rate of AF ablation. The one-stop procedure can improve cardiac function of the patients, but AF ablation alone can achieve better improvement of cardiac function.

Theory of Robot Mind: False Belief Attribution to Social Robots in Children With and Without Autism.

This study aims to probe how children with and without autism spectrum disorders (ASD) attribute false belief to a social robot and predict its action accordingly. Twenty 5- to 7-year-old children with ASD and 20 age- and IQ-matched typically developing (TD) children participated in two false belief tasks adapted for robot settings (change-of-location task and the unexpected-contents task). The results showed that most TD children are capable of attributing false belief to the social robot, that is, they could infer higher level mental states in robots, which extends our understanding in TD children's perception and cognition on social robots. Conversely, children with ASD still show difficulty in interpreting robots' mental states compared to their TD peers, which would greatly interfere with their interactions and communications with social robots and might impact on efficiency of robot-based intervention and education approaches. This group difference in attributing false belief to social robots could not be explained by the different perception and categorization of the robot. Our study implies that although children with ASD appear to be highly attracted by social robots, they still have difficulty in understanding mental states when socially interacting with robots, which should be taken into consideration when designing the robot-based intervention approach targeting to improve social behaviors of ASD.