TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway.

Liver cancer is the sixth most common cancer and the third leading cause of cancer-related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5-year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib-induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown-induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

Evaluation of a novel model incorporating serological indicators into the conventional TNM staging system for nasopharyngeal carcinoma.

BACKGROUND: Non-anatomical factors significantly affect treatment guidance and prognostic prediction in nasopharyngeal carcinoma (NPC) patients. Here, we developed a novel survival model by combining conventional TNM staging and serological indicators. METHODS: We retrospectively enrolled 10,914 eligible patients with nonmetastatic NPC over 2009-2017 and randomly divided them into training (n = 7672) and validation (n = 3242) cohorts. The new staging system was constructed based on T category, N category, and pretreatment serological markers by using recursive partitioning analysis (RPA). RESULTS: In multivariate Cox analysis, pretreatment cell-free Epstein-Barr virus (cfEBV) DNA levels of >2000 copies/mL [HROS (95 % CI) = 1.78 (1.57-2.02)], elevated lactate dehydrogenase (LDH) levels [HROS (95 % CI) = 1.64 (1.41-1.92)], and C-reactive protein-to-albumin ratio (CAR) of >0.04 [HROS (95 % CI) = 1.20 (1.07-1.34)] were associated with negative prognosis (all P < 0.05). Through RPA, we stratified patients into four risk groups: RPA I (n = 3209), RPA II (n = 2063), RPA III (n = 1263), and RPA IV (n = 1137), with 5-year overall survival (OS) rates of 93.2 %, 86.0 %, 80.6 %, and 71.9 % (all P < 0.001), respectively. Compared with the TNM staging system (eighth edition), RPA risk grouping demonstrated higher prognostic prediction efficacy in the training [area under the curve (AUC) = 0.661 vs. 0.631, P < 0.001] and validation (AUC = 0.687 vs. 0.654, P = 0.001) cohorts. Furthermore, our model could distinguish sensitive patients suitable for induction chemotherapy well. CONCLUSION: Our novel RPA staging model outperformed the current TNM staging system in prognostic prediction and clinical decision-making. We recommend incorporating cfEBV DNA, LDH, and CAR into the TNM staging system.

UBD participates in neutrophilic asthma by promoting the activation of IL-17 signaling.

Neutrophilic asthma is a persistent and severe inflammatory lung disease characterized by neutrophil activation and the mechanisms of which are not completely elucidated. Ubiquitin D (UBD) is a ubiquitin-like modifier participating in infections, immune responses, and tumorigenesis, while whether UBD involves in neutrophilic asthma needs further study. In this study, we initially found that UBD expression was significantly elevated and interleukin 17 (IL-17) signaling was enriched in the endobronchial biopsies of severe asthma along with neutrophils increasing by bioinformatics analysis. We further confirmed that UBD was upregulated in the lung tissues of neutrophilic asthma mouse model. UBD overexpression promoted IL-17 signaling activation. Knockdown of UBD suppressed the activation of IL-17 signaling. UBD interacted with TRAF2 and reduced the total and the K48-linked ubiquitination of TRAF2. However, IL-17 A stimulation increased both the total and the K48-linked ubiquitination of TRAF2. Together, these findings indicated that UBD was upregulated and played a critical role in IL-17 signaling which contributed to a better understanding of the complex mechanisms in neutrophilic asthma.

Leu promotes C2C12 cell differentiation by regulating the GSK3ß/ß-catenin signaling pathway through facilitating the interaction between SESN2 and RPN2.

BACKGROUND: Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment. RESULTS: Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3ß and increased nuclear ß-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3ß and decreased nuclear ß-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear ß-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells. CONCLUSION: Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3ß/ß-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.

Cold EMR vs. Hot EMR for the removal of sessile serrated polyps larger than 10 mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.

Structural insights into non-hotspot KRAS mutations and their potential as targets for effective cancer therapies.

Kirsten rat sarcoma virus protein (KRAS) is a protein that plays a central role in signal transduction using extracellular signal regulated kinase (ERK) and mitogen activated protein kinase (MAPK) cellular signaling pathway. KRAS is a frequently mutated oncogene and plays a pivotal role in tumor initiation and progression. Hotspot mutations on codon 12, 13 and 61 in KRAS are well-known for their role in drug resistance and non-hotspot mutations also play a significant part in contributing to resistance mechanisms. The understanding of how these non-hotspot mutations might affect the signal transduction of KRAS and their contribution towards drug resistance is understudied. Here we provide structural insights into the interaction of non-hotspot KRAS mutants with GTP (the native ligand) using a molecular docking and molecular dynamics simulation approach. Extensive molecular docking and simulation studies suggest that non-hotspot mutations (E31D and E63K) show stable interaction with native ligand using all five trajectories, as evidenced by root mean square of distance (RMSD), root mean square of fluctuation (RMSF), radius of gyration (RoG), coulomb short-range energy and MMGBSA analysis. These results suggest that non-hotspot mutations do not undermine the oncogenic nature of KRAS. This observation is consistent with previous findings where overexpressing E31D and E63K mutations share phenotypic features with G12D and G13D transfected cells, including increased proliferative capacity, actin cytoskeleton organization, and migration rates. We further test whether FDA-approved KRAS inhibitors sotorasib and adagrasib successfully inhibit the E31D and E63K mutants. Results suggest that these two non-hotspot mutants can be inhibited by both drugs with following trend of structural stability (E31D > E63K > wild-KRAS > Q61H > G12C). Based on sharp coherence in trajectories between wild KRAS and non-hotspot mutants, it is suggested that these novel mutants do not contribute to drug resistance mechanism. Overall, we provide a comprehensive understanding of the impact of non-hotspot mutations on KRAS and their potential as targets for effective cancer therapies.Communicated by Ramaswamy H. Sarma.

Counteracting mental fatigue for athletes: a systematic review of the interventions.

The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.

Research on Time Series Monitoring of Surface Deformation in Tongliao Urban Area Based on SBAS-PS-DS-InSAR.

As urban economies flourish and populations become increasingly concentrated, urban surface deformation has emerged as a critical factor in city planning that cannot be overlooked. Surface deformation in urban areas can lead to deformations in structural supports of infrastructure such as road bases and bridges, thereby posing a serious threat to public safety and creating significant safety hazards. Consequently, research focusing on the monitoring of urban surface deformation holds paramount importance. Interferometric synthetic aperture radar (InSAR), as an important means of earth observation, has all-day, wide-range, high-precision, etc., characteristics and is widely used in the field of surface deformation monitoring. However, traditional solitary InSAR techniques are limited in their application scenarios and computational characteristics. Additionally, the manual selection of ground control points (GCPs) is fraught with errors and uncertainties. Permanent scatterers (PS) can maintain high interferometric coherence in man-made building areas, and distributed scatterers (DS) usually show moderate coherence in areas with short vegetation; the combination of DS and PS solves the problem of manually selecting GCPs during track re-flattening and regrading, which affects the monitoring results. In this paper, 45 Sentinel-1B data from 16 February 2019 to 14 December 2021 are used as the data source in the urban area of Horqin District, Tongliao City, Inner Mongolia Autonomous Region, for example. A four-threshold (coherence coefficient threshold, FaSHPS adaptive threshold, amplitude divergence index threshold, and deformation velocity interval) GCPs point screening method for PS-DS, as well as a Small Baseline Subset-Permanent Scatterers-Distributed Scatterers-Interferometric Synthetic Aperture Radar (SBAS-PS-DS-InSAR) method for selecting PS and DS points as ground control points for orbit refinement and re-flattening, are proposed. The surface deformation results obtained using the Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) and the SBAS-PS-DS-InSAR proposed in this paper were comparatively analysed and verified. The maximum cumulative line-of-sight settlements were -90.78 mm and -83.68 mm, and the maximum cumulative uplifts are 74.94 mm and 97.56 mm, respectively; the maximum annual average line-of-sight settlements are -35.38 mm/y and -30.38 mm/y, and the maximum annual average uplifts are 25.27 mm/y and 27.92 mm/y. The results were evaluated and analysed in terms of correlation, mean absolute error (MAE), and root mean square error (RMSE). The deformation results of the two InSAR methods were evaluated and analysed in terms of correlation, MAE, and RMSE. The errors show that the Pearson correlation coefficients between the vertical settlement results obtained using the SBAS-PS-DS-InSAR method and the GPS monitoring results were closer to 1. The maximum MAE and RMSE were 13.7625 mm and 14.8004 mm, respectively, which are within the acceptable range; this confirms that the monitoring results of the SBAS-PS-DS-InSAR method were better than those of the original SBAS-InSAR method. SBAS-InSAR method, which is valid and reliable. The results show that the surface deformation results obtained using the SBAS-InSAR, SBAS-PS-DS-InSAR, and GPS methods have basically the same settlement locations, extents, distributions, and temporal and spatial settlement patterns. The deformation results obtained using these two InSAR methods correlate well with the GPS monitoring results, and the MAE and RMSE are within acceptable limits. By comparing the deformation information obtained using multiple methods, the surface deformation in urban areas can be better monitored and analysed, and it can also provide scientific references for urban municipal planning and disaster warning.

Multi-modality radiomics model predicts axillary lymph node metastasis of breast cancer using MRI and mammography.

OBJECTIVES: We aimed to develop a multi-modality model to predict axillary lymph node (ALN) metastasis by combining clinical predictors with radiomic features from magnetic resonance imaging (MRI) and mammography (MMG) in breast cancer. This model might potentially eliminate unnecessary axillary surgery in cases without ALN metastasis, thereby minimizing surgery-related complications. METHODS: We retrospectively enrolled 485 breast cancer patients from two hospitals and extracted radiomics features from tumor and lymph node regions on MRI and MMG images. After feature selection, three random forest models were built using the retained features, respectively. Significant clinical factors were integrated with these radiomics models to construct a multi-modality model. The multi-modality model was compared to radiologists' diagnoses on axillary ultrasound and MRI. It was also used to assist radiologists in making a secondary diagnosis on MRI. RESULTS: The multi-modality model showed superior performance with AUCs of 0.964 in the training cohort, 0.916 in the internal validation cohort, and 0.892 in the external validation cohort. It surpassed single-modality models and radiologists' ALN diagnosis on MRI and axillary ultrasound in all validation cohorts. Additionally, the multi-modality model improved radiologists' MRI-based ALN diagnostic ability, increasing the average accuracy from 70.70 to 78.16% for radiologist A and from 75.42 to 81.38% for radiologist B. CONCLUSION: The multi-modality model can predict ALN metastasis of breast cancer accurately. Moreover, the artificial intelligence (AI) model also assisted the radiologists to improve their diagnostic ability on MRI. CLINICAL RELEVANCE STATEMENT: The multi-modality model based on both MRI and mammography images allows preoperative prediction of axillary lymph node metastasis in breast cancer patients. With the assistance of the model, the diagnostic efficacy of radiologists can be further improved. KEY POINTS: • We developed a novel multi-modality model that combines MRI and mammography radiomics with clinical factors to accurately predict axillary lymph node (ALN) metastasis, which has not been previously reported. • Our multi-modality model outperformed both the radiologists' ALN diagnosis based on MRI and axillary ultrasound, as well as single-modality radiomics models based on MRI or mammography. • The multi-modality model can serve as a potential decision support tool to improve the radiologists' ALN diagnosis on MRI.

Effects of active video games on physical activity among overweight and obese college students: a systematic review.

Background: The purpose of this study was to critically review the existing literature on the effects of active video games (AVGs) on physical activity in overweight and obese college students to determine whether AVGs can promote and achieve recommended levels of physical activity. The results should provide constructive input for future research. Methods: A total of five international databases including PubMed, SCOPUS, Web of Science, CINAHL Plus, and EBSCOhost were searched with keywords related to "active video games," "physical activity," and "obese college students" from July 2022. A systematic review was conducted using the PRISMA guidelines and randomised controlled trial (RCT) studies that met the inclusion criteria were included. Furthermore, the quality assessment of the studies was measured using the PEDro scale. Results: One thousand and twenty-three articles were retrieved, of which eight randomised controlled trial studies met the inclusion criteria. AVGs can reduce sedentary behaviour and positively affect physical activity, time spent on moderate-to-vigorous physical activity (MVPA), positive psychological factors, and game attendance rate. Combining AVGs with other assistive devices (such as mini-trampolines and stationary bikes) can enhance the effects of AVGs and provide greater physiological stimulation. Different types of AVGs and game modes can achieve different emotional responses, physiological stimulation, and physical activity levels. Conclusion: The research findings prove that AVGs can be a viable intervention to increase physical activity in overweight or obese college students, ultimately reaching the recommended physical activity level(PAL). Physical activity can be further increased by incorporating assistive devices or using features supported by self-determination theory (SDT). As a new modality, AVGs could be a potential alternative to traditional physical activity.Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier: CRD42022363993.

Cytoskeletal Protein 4.1R in Health and Diseases.

The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin-actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts.

SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1.

Abnormal activation of the oncogene YAP in the Hippo pathway is a major feature in liver cancer and inactivation of MST1/2 has been shown to be responsible for the overactivation of YAP that led to tumorigenesis. However, mechanisms underlying MST1/2 dysregulation remain poorly understood. RNA-seq analysis and genome (KEGG) pathway enrichment analysis were used to identify genes and pathways that were regulated by SIRT7. qRT-PCR, ChIP, and luciferase assay were used to investigate transcriptional regulation. Mass spectrometry, co-immunoprecipitation and immunoprecipitation were used to exam protein-protein interaction and post-transcriptional modification. A xenograft mouse model was used to confirm the effect of SIRT7 and SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation in vivo. We found that SIRT7 suppresses MST1 by both transcriptional regulation and post-transcriptional modification, which in turn promotes YAP nuclear localization and transcriptional activation in liver cancer. Mechanistically, we revealed that SIRT7 suppresses MST1 transcription by binding to the MST1 promoter and inducing H3K18 deacetylation in its promoter region. In addition, SIRT7 directly binds to and deacetylates MST1, which primes acetylation-dependent MST1 ubiquitination and protein degradation. In clinical samples, we confirmed a negative correlation between SIRT7 and MST1 protein levels, and high SIRT7 expression correlated with elevated YAP expression and nuclear localization. In addition, SIRT7 specific inhibitor 2800Z sufficiently inhibited HCC growth by disrupting the SIRT7/MST1/YAP axis. Our data thus revealed the previously undescribed function of SIRT7 in regulating the Hippo pathway in HCC and further proved that targeting SIRT7 might provide novel therapeutic options for the treatment of liver cancer.

Ferritinophagy-mediated ferroptosis facilitates methotrexate-induced hepatotoxicity by high-mobility group box 1 (HMGB1).

BACKGROUND AND AIM: Hepatotoxicity is a well-defined reaction to methotrexate (MTX), a drug commonly used for the treatment of rheumatoid arthritis and various tumours. We sought to elucidate the mechanism underlying MTX-induced hepatotoxicity and establish a potentially effective intervention strategy. METHODS: We administered MTX to liver cells and mice and assessed hepatotoxicity by cell viability assay and hepatic pathological changes. We determined ferroptosis and ferritinophagy by detecting ferroptosis-related markers and autophagic degradation of ferritin heavy chain 1 (FTH1). RESULTS: We have shown that hepatocytes treated with MTX undergo ferroptosis, and this process can be attenuated by ferroptosis inhibitors. Interestingly, NCOA4-mediated ferritinophagy was found to be involved in MTX-induced ferroptosis, which was demonstrated by the relief of ferroptosis through the inhibition of autophagy or knockdown of Ncoa4. Furthermore, MTX treatment resulted in the elevation of high-mobility group box 1 (HMGB1) expression. The depletion of Hmgb1 in hepatocytes considerably alleviated MTX-induced hepatotoxicity by limiting autophagy and the subsequent autophagy-dependent ferroptosis. It is noteworthy that glycyrrhizic acid (GA), a precise inhibitor of HMGB1, effectively suppressed autophagy, ferroptosis and hepatotoxicity caused by MTX. CONCLUSION: Our study shows the significant roles of autophagy-dependent ferroptosis and HMGB1 in MTX-induced hepatotoxicity. It emphasizes that the inhibition of ferritinophagy and HMGB1 may have potential as a therapeutic approach for preventing and treating MTX-induced liver injury.

Associating Peritoneal Metastasis With T2-Weighted MRI Images in Epithelial Ovarian Cancer Using Deep Learning and Radiomics: A Multicenter Study.

BACKGROUND: The preoperative diagnosis of peritoneal metastasis (PM) in epithelial ovarian cancer (EOC) is challenging and can impact clinical decision-making. PURPOSE: To investigate the performance of T2 -weighted (T2W) MRI-based deep learning (DL) and radiomics methods for PM evaluation in EOC patients. STUDY TYPE: Retrospective. POPULATION: Four hundred seventy-nine patients from five centers, including one training set (N = 297 [mean, 54.87 years]), one internal validation set (N = 75 [mean, 56.67 years]), and two external validation sets (N = 53 [mean, 55.58 years] and N = 54 [mean, 58.22 years]). FIELD STRENGTH/SEQUENCE: 1.5 or 3 T/fat-suppression T2W fast or turbo spin-echo sequence. ASSESSMENT: ResNet-50 was used as the architecture of DL. The largest orthogonal slices of the tumor area, radiomics features, and clinical characteristics were used to construct the DL, radiomics, and clinical models, respectively. The three models were combined using decision-level fusion to create an ensemble model. Diagnostic performances of radiologists and radiology residents with and without model assistance were evaluated. STATISTICAL TESTS: Receiver operating characteristic analysis was used to assess the performances of models. The McNemar test was used to compare sensitivity and specificity. A two-tailed P < 0.05 was considered significant. RESULTS: The ensemble model had the best AUCs, outperforming the DL model (0.844 vs. 0.743, internal validation set; 0.859 vs. 0.737, external validation set I) and clinical model (0.872 vs. 0.730, external validation set II). After model assistance, all readers had significantly improved sensitivity, especially for those with less experience (junior radiologist1, from 0.639 to 0.820; junior radiologist2, from 0.689 to 0.803; resident1, from 0.623 to 0.803; resident2, from 0.541 to 0.738). One resident also had significantly improved specificity (from 0.633 to 0.789). DATA CONCLUSIONS: T2W MRI-based DL and radiomics approaches have the potential to preoperatively predict PM in EOC patients and assist in clinical decision-making. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

A tumor microenvironment-associated circRNA predictor for tumor relapse and chemotherapy vulnerability in nasopharyngeal carcinoma.

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

Primary choledocholithiasis occurrence and recurrence is synergetcally modulated by the bile microbiome and metabolome alternations.

AIMS: Primary choledocholithiasis is a common digestive disease with high morbidity and relapse. However, the compositions and functions of the bile microbial ecosystem and the pathogenesis of microfloral regulation of host metabolism resulting in stone formation are poorly understood. MAIN METHODS: Biliary samples collected from patients with acute cholangitis induced by benign biliary stricture (nonlithiasis group, n = 17) and primary choledocholithiasis (lithiasis group, n = 33) were subjected to multiomics analyses. Furthermore, clinicopathological features collected over a 24-month follow-up period were examined to evaluate the predictive value of candidate microbes. KEY FINDINGS: Five alpha diversity indices of the bile microbiome were significantly decreased in the lithiasis group. Furthermore, we identified 49 differential bile flora between the two groups, and the relative abundances of 6 bacteria, Actinobacteria, Actinobacteriota, Staphylococcales, Micrococcales, Altererythrobacter and Carnobacteriaceae, were associated with primary choledocholithiasis relapse conditions. Multiomics analyses showed that specific changes in disease-related bacterial taxa were closely related to metabolite variation (low-molecular weight carboxylic acids, sterol liquid and acylcarnitine), which might reflect disease prognosis. According to microbiomic and metabolomic pathway analyses, we revealed that bacterial infections, microbiota-derived amino acid metabolites and secondary bile acid-related pathways were significantly enriched in the stone-formation group, suggesting a novel host-microbial metabolic mechanism of primary choledocholithiasis. SIGNIFICANCE: Our study first indicates bile host-microbial dysbiosis modulates the abnormal accumulation of metabolites might further disrupt calcium homeostasis and generate insoluble saponification. Additionally, we determined the predictive value of Actinomycetes phylum reduction for recurrence in primary common bile duct stone patients.

A Second-Order Method for Removing Mixed Noise from Remote Sensing Images.

Remote sensing image denoising is of great significance for the subsequent use and research of images. Gaussian noise and salt-and-pepper noise are prevalent noises in images. Contemporary denoising algorithms often exhibit limitations when addressing such mixed noise scenarios, manifesting in suboptimal denoising outcomes and the potential blurring of image edges subsequent to the denoising process. To address the above problems, a second-order removal method for mixed noise in remote sensing images was proposed. In the first stage of the method, dilated convolution was introduced into the DnCNN (denoising convolutional neural network) network framework to increase the receptive field of the network, so that more feature information could be extracted from remote sensing images. Meanwhile, a DropoutLayer was introduced after the deep convolution layer to build the noise reduction model to prevent the network from overfitting and to simplify the training difficulty, and then the model was used to perform the preliminary noise reduction on the images. To further improve the image quality of the preliminary denoising results, effectively remove the salt-and-pepper noise in the mixed noise, and preserve more image edge details and texture features, the proposed method employed a second stage on the basis of adaptive median filtering. In this second stage, the median value in the original filter window median was replaced by the nearest neighbor pixel weighted median, so that the preliminary noise reduction result was subjected to secondary processing, and the final denoising result of the mixed noise of the remote sensing image was obtained. In order to verify the feasibility and effectiveness of the algorithm, the remote sensing image denoising experiments and denoised image edge detection experiments were carried out in this paper. When the experimental results are analyzed through subjective visual assessment, images denoised using the proposed method exhibit clearer and more natural details, and they effectively retain edge and texture features. In terms of objective evaluation, the performance of different denoising algorithms is compared using metrics such as mean square error (MSE), peak signal-to-noise ratio (PSNR), and mean structural similarity index (MSSIM). The experimental outcomes indicate that the proposed method for denoising mixed noise in remote sensing images outperforms traditional denoising techniques, achieving a clearer image restoration effect.

Effects of nitrogen inputs and mowing on the abundance and species richness of herbivorous insects in a meadow steppe.

To reveal the effects of nitrogen (N) inputs and mowing on the abundance and richness of insect community in meadow steppe, we investigated the abundance and diversity of herbivorous insects under four treatments in Inner Mongolia meadow steppe in August 2022, including control, N addition, mowing, and combined N addition and mowing. At a long-term control experimental platform, we collected insects using the vacuum sampling method. The results showed that N addition significantly increased the abundance of herbivorous insects, and mowing significantly decreased the abundance of herbivorous insects. Nitrogen addition significantly increased insect abundance in unmown condition but not in the mown condition. The responses of insect abundance at the community level to N addition were mainly driven by the dominant groups, Cicadellidae and Lygaeidae, which was affected by the abundance of Gramineae species. In contrast, their responses to mowing were the opposite. Both N addition and mowing did not affect the diversity of herbivorous insects. Our results indicated that the responses of herbivorous insect abundance to N inputs and mowing were directly regulated by food resources. With increasing food resource availability, the abundance but not the diversity of herbivorous insects increased, with stronger responses of dominant groups than subordinate ones.

[Microbial Community Composition and Diversity in Metal Sulfide Mine Water Systems].

To understand the characteristics of heavy metal pollution and physicochemical properties caused by mining activities in mine water systems and the response of the microbial community to habitats with different contamination levels, this study selected different types of water (mining area wastewater, spoil heap area wastewater, dressing area wastewater, mine seepage water, and pond water) as the variables related to the mining activities in the water system of the Shizishan mining area in Tongling, Anhui Province. The pollution characteristics and physicochemical properties were compared, and the relationship between environmental factors and the microbial communities were analyzed. The results showed that the content of heavy metals, the physicochemical properties, and the structure and diversity of the microbial community of different types of water were significantly different in different mine areas, among which the most seriously polluted areas were the mining area, the spoil heap area, and the dressing area. There were significant differences in microbial community structure among different functional types of wastewaters, and the diversity and abundance of the microbial community in DW with the heaviest heavy metal pollution were weaker than those in the other four regions. PcoA analysis showed that samples of similar water types had similar clustering. Spearman correlation heat map analysis and canonical correlation analysis (CCA) indicated that heavy metal pollution, pH, electrical conductivity (EC), SO2-4, and chemical oxygen demand (COD) had the greatest effect on the microbial communities in the mine water systems. Moreover, this study found that Proteobacteria, Euryarchaeota, and Bacteroidetes dominated in mine water systems, and their potential use could be explored in the future. Our results provide a better understanding of the different types of water pollution characteristics in mine water systems and the key factors that determine the microbial community structure.