The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

IGF2BP3 aggravates lung adenocarcinoma progression by modulation of PI3K/AKT signaling pathway.

OBJECTIVES: The tumor-promoting function of IGF2BP3 has been reported in several cancers. The present study aimed to explore the function and molecular mechanisms of IGF2BP3 are elusive in lung adenocarcinoma (LUAD). METHODS: IGF2BP3 expression in LUAD and its prognostic value were estimated by bioinformatics. RT-qPCR was employed to detect the expression of IGF2BP3 and confirm the transfection efficiency following the knockdown or overexpression of IGF2BP3. Functional assays, including CCK-8, TUNEL, and Transwell assays, were used to determine the role of IGF2BP3 in tumor cell viability, apoptosis, migration and invasion. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to IGF2BP3 expression. The effects of IGF2BP3 on the PI3K/AKT pathway were detected by western blotting. RESULTS: In this study, we found that IGF2BP3 was overexpressed in LUAD, and patients with high IGF2BP3 levels had a lower probability of overall survival. Moreover, ectopic expression of IGF2BP3 enhanced cell viability and metastasis, and reduced apoptosis. Conversely, IGF2BP3 silencing reduced the viability, migration, and invasion while enhancing the apoptosis of LUAD cells. In addition, it was disclosed that overexpression of IGF2BP3 could activate PI3K/AKT signaling in LAUD, while silencing of IGF2BP3 deactivated this pathway. Moreover, 740Y-P (PI3K agonist) reversed the inhibitory effects on cell viability and metastasis, and the promotion effect on metastasis caused by IGF2BP3 silencing. CONCLUSION: Our findings demonstrated that IGF2BP3 contributed to the tumorigenesis of LUAD by activating the PI3K/AKT signaling.

Role of hemoglobin alpha and hemoglobin beta in non-small-cell lung cancer based on bioinformatics analysis.

The differentially expressed genes (DEGs) were identified and screened differentially in non-small-cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein-protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin-binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand-receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.

Persistent Abnormal Immunocytes Induced Systemic Bone Loss in Locally Irradiated Rats.

Chronic and systemic bone complications frequently occur in patients who undergo radiotherapy; however, the pathological mechanisms underlying these complications remain unclear. This study aimed to observe persistent and systemic changes in locally irradiated rats and to determine the systemic pathological changes that persistently affect bone metabolism. We examined the inflammatory and oxidative stress responses that occurred after local irradiation using enzyme immunoassays and biochemical analyses. Lymphocytes obtained from the blood, spleen, thymus, and bone marrow were evaluated using flow cytometry. The proliferation and apoptosis characteristics of co-cultured bone marrow-derived mesenchymal stem cells (BMSCs) were detected by MTT assay and PI/Annexin V-FITC staining, respectively, and the differentiation of BMSCs was measured according to alkaline phosphatase (ALP) staining, alizarin red staining, and Oil Red O staining and by evaluating the mRNA expression of ALP, osteocalcin (OCN), osteopontin (OPN), collagen I, Runx2, and PPARγ. Our results revealed that no significant or continuous differences were present in the inflammatory response or the oxidative stress response throughout the body after local irradiation. B lymphocyte levels increased continuously in the blood, spleen, and bone marrow after local irradiation. T lymphocyte levels were decreased at 2 weeks after local irradiation, and CD8+T lymphocyte levels were increased in the blood, thymus, and bone marrow at 12 weeks after local irradiation. The ratio of CD4+/CD8+T lymphocytes began to decrease during the early phase after local irradiation and became significantly decreased at 12 weeks after local irradiation. Normal BMSCs co-cultured with lymphocytes derived from irradiated rats exhibited decreased proliferation and increased apoptosis, and the ALP staining intensity, alizarin red staining intensity, and mRNA expression of related genes were all also decreased. Oil Red O staining intensity and mRNA expression of PPARγ were both increased. Lymphocyte levels contribute to chronic and systemic bone complications after radiotherapy by inhibiting the proliferation and osteoblastogenesis of BMSCs.

PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.

Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.

[CT imaging features of patients with different clinical types of COVID-19].

OBJECTIVE: To investigate the CT findings of patients with different clinical types of coronavirus disease 2019 (COVID-19). METHODS: A total of 67 patients diagnosed as COVID-19 by nucleic acid testing were collected and divided into 4 groups according to the clinical stages based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6). The CT imaging characteristics were analyzed among patients with different clinical types. RESULTS: Among 67 patients, 3(4.5%) were mild, 35 (52.2%) were moderate, 22 (32.8%) were severe, and 7(10.4%) were critical ill. No significant abnormality in chest CT imaging in mild patients. The 35 cases of moderate type included 3 (8.6%) single lesions, the 22 cases of severe cases included 1 (4.5%) single lesion and the rest cases were with multiple lesions. CT images of moderate patients were mainly manifested by solid plaque shadow and halo sign (18/35, 51.4%); while fibrous strip shadow with ground glass shadow was more frequent in severe cases (7/22, 31.8%). Consolidation shadow as the main lesion was observed in 7 cases, and all of them were severe or critical ill patients. CONCLUSIONS: CT images of patients with different clinical types of COVID-19 have characteristic manifestations, and solid shadow may predict severe and critical illness.

[Dynamic changes of chest CT imaging in patients with COVID-19].

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation.

The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells.

Impact of intra-operative cholangiography and parenchymal resection to donor liver function in living donor liver transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) has been widely accepted over the past decade, and hepatic dysfunction often occurs in the donor in the early stage after liver donation. The present study aimed to evaluate the effect of intra-operative cholangiography (IOC) and parenchymal resection on liver function of donors in LDLT, and to assess the role of IOC in influencing the biliary complications and improving the overall outcome. METHODS: Data from 40 patients who had donated their right lobes for LDLT were analyzed. Total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) at different time points were compared, and the follow-up data and the biliary complications were also analyzed. RESULTS: The ALT and AST values were significantly increased after IOC (P<0.001) and parenchymal resection (P<0.001). However, the median values of TB, ALP and GGT were not significantly influenced by IOC (P>0.05) or parenchymal resection (P>0.05). The biochemical changes caused by IOC or parenchymal resection were not correlated with the degree of post-operative liver injury or the recovery of liver function. The liver functions of the donors after operation were stable, and none of the donors suffered from biliary stenosis or leakage during the follow-up. CONCLUSIONS: IOC and parenchymal resection may induce a transient increase in liver enzymes of donors in LDLT, but do not affect the recovery of liver function after operation. Moreover, the routine IOC is helpful to clarify the division line of the hepatic duct, thus reducing the biliary complication rate.

Preoperative Physical Dysfunction Characteristics and Influence Factors Among Elderly Patients with Early Lung Cancer: A Latent Class Analysis.

Objective: To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes. Methods: We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class. Results: The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into "Anxiety/depression emotion-poor sleep group" "Frailty of physical function group" "Pulmonary hypofunction-low activity tolerance group". The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P<0.05). The elderly lung cancer patients with chronic disease history and age ≥75 years were more likely to be classified as "frailty of physical function group". The elderly lung cancer patients with COPD and smoking history were more likely to be classified into "pulmonary hypofunction-low activity tolerance group". Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into "anxiety/depression emotion-poor sleep group". Conclusion: The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.

MicroRNA­373­3p inhibits the proliferation and invasion of non­small­cell lung cancer cells by targeting the GAB2/PI3K/AKT pathway.

MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.

Exploring the biological basis of CT imaging features in pancreatic neuroendocrine tumors: a two-center study.

Objective.Medical imaging offered a non-invasive window to visualize tumors, with radiomics transforming these images into quantitative data for tumor phenotyping. However, the intricate web linking imaging features, clinical endpoints, and tumor biology was mostly uncharted. This study aimed to unravel the connections between CT imaging features and clinical characteristics, including tumor histopathological grading, clinical stage, and endocrine symptoms, alongside immunohistochemical markers of tumor cell growth, such as the Ki-67 index and nuclear mitosis rate.Approach.We conducted a retrospective analysis of data from 137 patients with pancreatic neuroendocrine tumors who had undergone contrast-enhanced CT scans across two institutions. Our study focused on three clinical factors: pathological grade, clinical stage, and endocrine symptom status, in addition to two immunohistochemical markers: the Ki-67 index and the rate of nuclear mitosis. We computed both predefined (2D and 3D) and learning-based features (via sparse autoencoder, or SAE) from the scans. To unearth the relationships between imaging features, clinical factors, and immunohistochemical markers, we employed the Spearman rank correlation along with the Benjamini-Hochberg method. Furthermore, we developed and validated radiomics signatures to foresee these clinical factors.Main results.The 3D imaging features showed the strongest relationships with clinical factors and immunohistochemical markers. For the association with pathological grade, the mean absolute value of the correlation coefficient (CC) of 2D, SAE, and 3D features was 0.3318 ± 0.1196, 0.2149 ± 0.0361, and 0.4189 ± 0.0882, respectively. While for the association with Ki-67 index and rate of nuclear mitosis, the 3D features also showed higher correlations, with CC as 0.4053 ± 0.0786 and 0.4061 ± 0.0806. In addition, the 3D feature-based signatures showed optimal performance in clinical factor prediction.Significance.We found relationships between imaging features, clinical factors, and immunohistochemical markers. The 3D features showed higher relationships with clinical factors and immunohistochemical markers.

Pulmonary sarcomatoid carcinoma: a case report.

Sarcomatoid carcinoma (SC) is a rare primary malignant tumor in which both carcinomatous and sarcomatous elements occur. It can occur in many different organs and anatomical locations, such as the skin, thyroid gland, bone, urinary tract, breast, pancreas, liver and other areas. Of them, pulmonary sarcomatoid carcinoma (PSC) is a rare malignant cancer composed of sarcoma and sarcoma-like tumors with spindle or giant cell features. Here a case of a 75-year-old Chinese man with a six-month history of cough and hemoptysis is reported. Chest X-ray showed a tumor shadow in the left lung field. Chest computed tomography (CT) scan showed a lobulated mass in his left hilum and even the left pulmonary artery. Pleomorphic interstitial cells were found by bronchoscopic brushing. To establish a definitive diagnosis for PSC, a left pneumonectomy was performed. The pathological stage was IIB (pT2N1M0) based on the tumor node metastasis (TNM) staging system. The tumor's pathology, histology, immunohistochemistry and treatment methods are discussed.

A novel investigation into an E2F transcription factor-related prognostic model with seven signatures for colon cancer patients.

The pathogenesis of colon cancer, a common gastrointestinal tumour, involves complicated factors, especially a series of cell cycle-related genes. E2F transcription factors during the cell cycle play an essential role in the occurrence of colon cancer. It is meaningful to establish an efficient prognostic model of colon cancer targeting cellular E2F-associated genes. This has not been reported previously. The authors first aimed to explore the links of E2F genes with the clinical outcomes of colon cancer patients by integrating data from the TCGA-COAD (n = 521), GSE17536 (n = 177) and GSE39582 (n = 585) cohorts. The Cox regression and Lasso modelling approach to identify a novel colon cancer prognostic model involving several hub genes (CDKN2A, GSPT1, PNN, POLD3, PPP1R8, PTTG1 and RFC1) were utilised. Moreover, an E2F-related nomogram that efficiently predicted the survival rates of colon cancer patients was created. Additionally, the authors first identified two E2F tumour clusters, which showed distinct prognostic features. Interestingly, the potential links of E2F-based classification and 'protein secretion' issues of multiorgans and tumour infiltration of 'T-cell regulatory (Tregs)' and 'CD56dim natural killer cell' were detected. The authors' findings are of potential clinical significance for the prognosis assessment and mechanistic exploration of colon cancer.

CT radiomics for noninvasively predicting NQO1 expression levels in hepatocellular carcinoma.

Using noninvasive radiomics to predict pathological biomarkers is an innovative work worthy of exploration. This retrospective cohort study aimed to analyze the correlation between NAD(P)H quinone oxidoreductase 1 (NQO1) expression levels and the prognosis of patients with hepatocellular carcinoma (HCC) and to construct radiomic models to predict the expression levels of NQO1 prior to surgery. Data of patients with HCC from The Cancer Genome Atlas (TCGA) and the corresponding arterial phase-enhanced CT images from The Cancer Imaging Archive were obtained for prognosis analysis, radiomic feature extraction, and model development. In total, 286 patients with HCC from TCGA were included. According to the cut-off value calculated using R, patients were divided into high-expression (n = 143) and low-expression groups (n = 143). Kaplan-Meier survival analysis showed that higher NQO1 expression levels were significantly associated with worse prognosis in patients with HCC (p = 0.017). Further multivariate analysis confirmed that high NQO1 expression was an independent risk factor for poor prognosis (HR = 1.761, 95% CI: 1.136-2.73, p = 0.011). Based on the arterial phase-enhanced CT images, six radiomic features were extracted, and a new bi-regional radiomics model was established, which could noninvasively predict higher NQO1 expression with good performance. The area under the curve (AUC) was 0.9079 (95% CI 0.8127-1.0000). The accuracy, sensitivity, and specificity were 0.86, 0.88, and 0.84, respectively, with a threshold value of 0.404. The data verification of our center showed that this model has good predictive efficiency, with an AUC of 0.8791 (95% CI 0.6979-1.0000). In conclusion, there existed a significant correlation between the CT image features and the expression level of NQO1, which could indirectly reflect the prognosis of patients with HCC. The predictive model based on arterial phase CT imaging features has good stability and diagnostic efficiency and is a potential means of identifying the expression level of NQO1 in HCC tissues before surgery.

Characterization and the cholesterol-lowering effect of dietary fiber from fermented black rice (Oryza sativa L.).

Black rice was fermented with Neurospora crassa, after which the dietary fiber (DF) extracted from it was characterized and evaluated for its cholesterol-lowering effect in mice. The findings demonstrated that fermentation increased the level of soluble DF from 17.27% ± 0.12 to 29.69% ± 0.26 and increased the adsorption capacity of DF for water, oil, cholesterol, glucose and sodium cholate. The fermented DF had a more loose and porous structure than that extracted from unfermented rice. Additionally, feeding with DF from the fermented black rice significantly reduced body weight, lowered total cholesterol levels and improved the lipid profile in mice gavaged with a high dose (5 g per kg bw) or a low dose (2.5 g per kg·bw). ELISA showed that the hepatic expression of typical proteins and enzymes that are involved in cholesterol metabolism was regulated by the fermented rice DF, leading to reduced cholesterol production and increased cholesterol clearance. The fermented DF also modified the gut microbiota composition (e.g. Firmicutes reduced and Akkermansia increased), which promoted the production of short-chain fatty acids. In conclusion, fermentation can modify the structure and function of DF in black rice and the fermented dietary fiber has excellent cholesterol lowering effects possibly by cholesterol adsorption, cholesterol metabolism modulation, and intestinal microflora regulation.

Deciphering the role of extrachromosomal circular DNA in adipose stem cells from old and young donors.

BACKGROUND: The functional impairment of adipose stem cells (ASCs) during aging limits their clinical transformation. Studies have shown that extrachromosomal circular DNAs (eccDNAs) are associated with tumor progression and cell aging, but the roles of eccDNAs in ASCs remain unknown. METHOD: We conducted Circle sequencing (Circle-seq) to identify eccDNAs in ASCs isolated from young and old donors. The differentially expressed eccDNAs were calculated, annotated and validated via polymerase chain reaction. RESULTS: Thousands of eccDNAs were identified and comprehensively characterized. Most of them were GC-rich, < 1000 base pairs in size, and were enriched on chromosome 19 and 17 with a high density of Alu elements and genes, 2 kb upstream/downstream of genes and satellites. In total, 3025 eccDNAs were differentially expressed among the two ASC groups. Conjoint analysis of the Circle-seq results and previous RNA-seq results revealed that 73 eccDNAs and 55 genes exhibited the same differential expression between the two groups. KEGG and GO analyses revealed that genes encoding differentially expressed eccDNAs were enriched for cell adhesion, cellular senescence and TGF-ß receptor signaling pathway. We also found that aged ASCs exhibited loss of eccDNAs, including CAMK2G (chr10: 75577899-75578176), TRABD2B (chr1: 48305638-48307008) and TRABD2B (chr1: 48305425-48307091). CONCLUSION: In this study, we elucidated the first eccDNA profile relating to ASCs and demonstrated that three eccDNAs are lost in aged ASCs, which may be potential biomarkers of stem cell aging and valuable targets for stem cell rejuvenation.

Application of multi-modality MRI-based radiomics in the pre-treatment prediction of RPS6K expression in hepatocellular carcinoma.

In this study, we aim to develop and validate a radiomics model for pretreatment prediction of RPS6K expression in hepatocellular carcinoma (HCC) patients, thus helping clinical decision-making of mTOR-inhibitor (mTORi) therapy. We retrospectively enrolled 147 HCC patients, who underwent curative hepatic resection at First Affiliated Hospital Zhejiang University School of Medicine. RPS6K expression was determined with immunohistochemistry staining. Patients were randomly split into training or validation cohorts on a 7:3 ratio. Radiomics features were extracted from T2-weighted and diffusion-weighted images. Machine learning algorithms including multiple logistic regression (MLR), supporting vector machine (SVM), random forest (RF), and artificial neural network (ANN) were applied to construct the predictive model. A nomogram was further built to visualize the possibility of RPS6K expression. The area under the receiver operating characteristic (AUC) was used to evaluate the performance of diagnostic models. 174 radiomics features were confirmed correlated with RPS6K expression. Amongst all built models, the ANN-based hybrid model exhibited best predictive ability with AUC of 0.887 and 0.826 in training and validation cohorts. ALB was identified as the key clinical index, and the nomogram displayed further improved ability with AUC of 0.917 and 0.845. In this study, we proved MRI-based radiomics model and nomogram can accurately predict RPS6K expression non-invasively, thus providing help for clinical decision making for mTORi therapy.

Small Is Beautiful: Compressing Deep Neural Networks for Partial Domain Adaptation.

Domain adaptation is a promising way to ease the costly data labeling process in the era of deep learning (DL). A practical situation is partial domain adaptation (PDA), where the label space of the target domain is a subset of that in the source domain. Although existing methods yield appealing performance in PDA tasks, it is highly presumable that computation overhead exists in deep PDA models since the target is only a subtask of the original problem. In this work, PDA and model compression are seamlessly integrated into a unified training process. The cross-domain distribution divergence is reduced by minimizing a soft-weighted maximum mean discrepancy (SWMMD), which is differentiable and functions as regularization during network training. We use gradient statistics to compress the overparameterized model to identify and prune redundant channels based on the corresponding scaling factors in batch normalization (BN) layers. The experimental results demonstrate that our method can achieve comparable classification performance to state-of-the-art methods on various PDA tasks, with a significant reduction in model size and computation overhead.

Stratified treatment of localized cervical esophageal squamous cell carcinoma induced by neoadjuvant immunotherapy plus chemotherapy (SCENIC).

Background: Definitive chemoradiation is the preferred treatment for cervical esophageal carcinoma (CEC), per the National Comprehensive Cancer Network (NCCN) guidelines. However, in treatment failures, salvage surgery poses significant technical challenges. If non-responders could be identified, prior to chemoradiation, these patients may benefit from primary esophagectomy. Programmed cell death protein 1 (PD-1) inhibitor is widely used and recognized as an effective treatment method in various cancers including esophageal cancer. Therefore, we propose to screen for treatment response to neoadjuvant immunotherapy plus chemotherapy to select patients who are radiosensitive and potential candidates for laryngeal preservation. While non-responders are likely to be insensitive to chemoradiation would be offered radical esophagectomy. Methods: A total of 36 patients with histopathologically-confirmed locally advanced CEC have been enrolled in our study. All participants will receive 2 cycles of induction therapy, which was tislelizumab combined with paclitaxel and carboplatin. Patients will be classified into 3 groups according to their response to induction therapy: a remarkable response (RR) group, limited partial response (LPR) group, and poor response (POR) group. Stratified patients will receive the following follow-up treatments: those in the RR group will receive dCRT, and those in the LPR and POR groups will undergo radical surgery. Then, participants in the RR group will be administrated with tislelizumab alone for 1 year. The choice of postoperative treatment for patients in the LPR and POR groups will depend on the patient's condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint of the study is the 2-year event-free survival (EFS). The secondary endpoints are disease-free survival (DFS), regression-free survival (RFS), objective response rate (ORR), and 5-year overall survival (OS). At the same time, we will assess the patient's quality of life (QoL). Conclusions: Screening CEC patients after immune-induction therapy combined with chemotherapy using different treatment strategies might lead to improvements in their QoL and OS time. No relevant double-endpoint studies have been reported until now. Our study is the first multicenter, prospective, exploratory study to seek the optimal treatment for locally advanced CEC patients. The results may offer high-level evidence for future CEC treatment. Trial Registration: Chictr.Org identifier: ChiCTR2200057732.