HiTE: a fast and accurate dynamic boundary adjustment approach for full-length transposable element detection and annotation.

Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods for TE annotation using genome assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, the currently available gold-standard TE databases are not comprehensive, even for extensively studied species, highlighting the critical need for an automated TE detection method to supplement existing repositories. In this study, we introduce HiTE, a fast and accurate dynamic boundary adjustment approach designed to detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, the state-of-the-art tool, across various species. Furthermore, HiTE has identified numerous novel transposons with well-defined structures containing protein-coding domains, some of which are directly inserted within crucial genes, leading to direct alterations in gene expression. A Nextflow version of HiTE is also available, with enhanced parallelism, reproducibility, and portability.

Non-alcoholic fatty liver disease: pathogenesis and models.

Non-alcoholic fatty liver disease (NAFLD) is a complex disease characterized by a massive accumulation of lipids in the liver, with a continuous progression of simple steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is associated with obesity, insulin resistance, and metabolic syndrome; it is a severe public health risk and is currently the most common liver disease of the world. In addition to the fatty infiltration of the liver in non-alcoholic fatty liver disease patients, the field of liver transplantation faces similar obstacles. NAFLD and NASH primarily involve lipotoxicity, inflammation, oxidative stress, and insulin resistance. However, the precise mechanisms and treatments remain unclear. Therapeutic approaches encompass exercise, weight control, as well as treatments targeting antioxidants and anti-inflammatory pathways. The role of animal models in research has become crucial as a key tool to explore the molecular mechanisms and potential treatments for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Here, we summarized the current understanding of the pathogenesis of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis and discussed animal models commonly used in recent years.

A First-Principles Study of Mechanical and Electronic Properties of Cr0.5-xAl0.5TMxN Hard Coatings (TM = Ti, V, Y, Zr, Hf, and Ta).

The structural, mechanical, and electronic properties of cubic Cr0.5-xAl0.5TMxN, doped with TM (transition metal) elements (TM = Ti, V, Y, Zr, Hf, and Ta) at low concentrations (x = 0.03 and 0.06), was investigated by first-principles calculations. The results of the structural properties calculations reveal that the addition of Ti, Y, Hf, Zr, and Ta expand the volume, while V has the opposite effect. All doped compounds are thermodynamically stable, and Cr0.5-xAl0.5TMxN with TM = Ti is energetically more favorable than other doped compounds. At the same doping concentration, Cr0.5-xAl0.5VxN possesses the highest stiffness, hardness, and resistance to external forces due to its greatest mechanical properties, and Cr0.5-xAl0.5TaxN possesses the highest elastic anisotropy and the lowest Young's modulus. Substituting Cr atoms with TM atoms in a stepwise manner results in a decrease in the bulk modulus, shear modulus, Young's modulus, and theoretical hardness of Cr0.5-xAl0.5TMxN, while increasing its toughness. Based on the calculation results of the total and partial density of states of Cr0.5Al0.5N and Cr0.47Al0.5TM0.03N, all compounds exhibit metallic behavior as indicated by the finite density of states at the Fermi level. The contribution of Ti-3d, V-3d, and Ta-3d orbitals at Fermi level is significantly higher than that of other TM atoms, resulting in a more pronounced metallic character for Cr0.47Al0.5Ti0.03N, Cr0.47Al0.5V0.03N, and Cr0.47Al0.5Ta0.03N.

Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study.

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

Radiomics based on T2-weighted and diffusion-weighted MR imaging for preoperative prediction of tumor deposits in rectal cancer.

AIM: Preoperative diagnosis of tumor deposits (TDs) in patients with rectal cancer remains a challenge. This study aims to develop and validate a radiomics nomogram based on the combination of T2-weighted (T2WI) and diffusion-weighted MR imaging (DWI) for the preoperative identification of TDs in rectal cancer. MATERIALS AND METHODS: A total of 199 patients with rectal cancer who underwent T2WI and DWI were retrospectively enrolled and divided into a training set (n â€‹= â€‹159) and a validation set (n â€‹= â€‹40). The total incidence of TDs was 37.2 â€‹% (74/199). Radiomics features were extracted from T2WI and apparent diffusion coefficient (ADC) images. A radiomics nomogram combining Rad-score (T2WI â€‹+ â€‹ADC) and clinical factors was subsequently constructed. The area under the receiver operating characteristic curve (AUC) was then calculated to evaluate the models. The nomogram is also compared to three machine learning model constructed based on no-Rad scores. RESULTS: The Rad-score (T2WI â€‹+ â€‹ADC) achieved an AUC of 0.831 in the training and 0.859 in the validation set. The radiomics nomogram (the combined model), incorporating the Rad-score (T2WI â€‹+ â€‹ADC), MRI-reported lymph node status (mLN-status), and CA19-9, showed good discrimination of TDs with an AUC of 0.854 for the training and 0.923 for the validation set, which was superior to Random Forests, Support Vector Machines, and Deep Learning models. The combined model for predicting TDs outperformed the other three machine learning models showed an accuracy of 82.5 â€‹% in the validation set, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 66.7 â€‹%, 92.0 â€‹%, 83.3 â€‹%, and 82.1 â€‹%, respectively. CONCLUSION: The radiomics nomogram based on Rad-score (T2WI â€‹+ â€‹ADC) and clinical factors provides a promising and effective method for the preoperative prediction of TDs in patients with rectal cancer.

CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases. VAMP8 expression was significantly increased after knockdown of CENPN by transcriptome sequencing. We found in cell experiments that CENPN inhibited macroautophagy/autophagy and VAMP8 expression and significantly increased PTX resistance. Overexpression of CENPN reduced the inhibitory effects of PTX on survival, cell proliferation, cell cycle progression and apoptosis resistance in NPC cells by inhibiting autophagy. In turn, knockdown of CENPN can affect the phenotype of NPC cells by increasing autophagy to achieve PTX sensitization. Sequential knockdown of CENPN and VAMP8 reversed the PTX-sensitizing effect of CENPN knockdown alone. Experiments in nude mice confirmed that knockdown of CENPN can increase VAMP8 expression, enhance autophagy and increase the sensitivity of NPC cells to PTX. Mechanistic studies showed that CENPN inhibited the translocation of p-CREB into the nucleus of NPC cells, resulting in the decreased binding of p-CREB to the VAMP8 promoter, thereby inhibiting the transcription of VAMP8. These results demonstrate that CENPN may be a marker for predicting chemotherapeutic efficacy and a potential target for inducing chemosensitization to agents such as PTX.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; CENPN: centromere protein N; CQ: chloroquine; CREB: cAMP responsive element binding protein; ChIP: chromatin immunoprecipitation assay; IC50: half-maximal inhibitory concentration; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPC: nasopharyngeal carcinoma; NPG: nasopharyngitis; oeCENPN: overexpressed CENPN; PTX: paclitaxel; RAPA: rapamycin; RNA-seq: transcriptome sequencing; shCENPN: small hairpin RNA expression vector targeting the human CENPN gene; shCENPN-shVAMP8: sequential knockdown targeting the human CENPN gene and VAMP8 gene; shVAMP8: small hairpin RNA expression vector targeting the human VAMP8 gene; TEM: transmission electron microscopy; TIR: tumor inhibitory rate; VAMP8: vesicle associated membrane protein 8.

A Novel Nomogram to Predict Resectable Gastric Cancer Based on Preoperative Circulating Tumor Cell.

INTRODUCTION: Circulating tumor cells (CTCs) have been suggested to have an important prognostic role in gastrointestinal tumors. We developed a preoperative CTC-based nomogram to predict the prognosis of patients with resectable gastric cancer after surgery and established a risk stratification system based on the nomogram. METHODS: From January 2012 to June 2017, we screened 258 patients with gastric cancer treated with surgery from one center as the training cohort and 133 patients with gastric cancer treated with surgery from another as the validation cohort, screened prognostic factors for the training cohort using univariate and multivariate Cox risk proportional models, created predictive overall survival (OS) and a recurrence-free survival (RFS) nomogram, and plotted the receiver operating characteristic curve and calibration curve for this nomogram in the training and validation cohorts. Risk score stratification was performed according to the nomogram, and OS curves were plotted for the low, medium, and high-risk groups using the Kaplan-Meier method. RESULTS: The CTC positivity rate was 78.5% in all patients. CTC, TNM stage, and Ki-67 were the prognostic factors affecting OS and RFS after gastric cancer surgery. The nomogram consisted of these 3 variables. In the training group, the area under the curve of the nomogram for OS at 1, 3, and 5 years was 0.918, 0.829, and 0.813, respectively, and the area under the curve for RFS was 0.900, 0884, and 0.839, respectively. There was a statistically significant difference in OS among the low, medium, and high-risk groups according to the risk stratification system constructed from nomogram scores ( P < 0.001). DISCUSSION: Two nomograms based on preoperative CTC were established to predict OS and RFS after resectable gastric cancer. The 2 nomograms had good discrimination and calibration and significant stratification ability of the risk stratification system established according to them.

Gut microbial structural variation associates with immune checkpoint inhibitor response.

The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.

Photochemical reductive deamination of alpha-amino aryl alkyl ketones.

Photochemical reductive deamination of alpha-amino aryl alkyl ketones under photosensitizer-free conditions is presented. This protocol features high efficiency and selectivity. A plausible reaction pathway is proposed based on ultraviolet-visible absorption investigation, control experiments and deuterium-labelling studies. Mechanistic study reveals that the alpha-hydrogen atom of the ketone product originated from water.

Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.

OBJECTIVE: Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS: Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm3, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques. RESULTS: The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm3 and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm3 and 0.04 ± 0.01 g. CONCLUSION: Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.