DIRMC: a database of immunotherapy-related molecular characteristics.

Cancer immunotherapy has brought about a revolutionary breakthrough in the field of cancer treatment. Immunotherapy has changed the treatment landscape for a variety of solid and hematologic malignancies. To assist researchers in efficiently uncovering valuable information related to cancer immunotherapy, we have presented a manually curated comprehensive database called DIRMC, which focuses on molecular features involved in cancer immunotherapy. All the content was collected manually from published literature, authoritative clinical trial data submitted by clinicians, some databases for drug target prediction such as DrugBank, and some experimentally confirmed high-throughput data sets for the characterization of immune-related molecular interactions in cancer, such as a curated database of T-cell receptor sequences with known antigen specificity (VDJdb), a pathology-associated TCR database (McPAS-TCR) et al. By constructing a fully connected functional network, ranging from cancer-related gene mutations to target genes to translated target proteins to protein regions or sites that may specifically affect protein function, we aim to comprehensively characterize molecular features related to cancer immunotherapy. We have developed the scoring criteria to assess the reliability of each MHC-peptide-T-cell receptor (TCR) interaction item to provide a reference for users. The database provides a user-friendly interface to browse and retrieve data by genes, target proteins, diseases and more. DIRMC also provides a download and submission page for researchers to access data of interest for further investigation or submit new interactions related to cancer immunotherapy targets. Furthermore, DIRMC provides a graphical interface to help users predict the binding affinity between their own peptide of interest and MHC or TCR. This database will provide researchers with a one-stop resource to understand cancer immunotherapy-related targets as well as data on MHC-peptide-TCR interactions. It aims to offer reliable molecular characteristics support for both the analysis of the current status of cancer immunotherapy and the development of new immunotherapy. DIRMC is available at http://www.dirmc.tech/. Database URL: http://www.dirmc.tech/.

The bi-directional relationships between diversified leisure activity participation and cognitive function in older adults in China: separating between-person effects from within-person effects.

OBJECTIVE: To examine the bi-directorial association between diversified leisure activity participation and cognitive function over a 7-year period. METHODS: Data analyzed was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a large-scale longitudinal national study. The baseline survey was conducted in 2011 with follow-up every three years. We traced a total of 2718 participants over a period of 7 years. We used adjusted random intercept cross-lagged panel models (RI-CLPMs) to examine the bi-directorial associations between diversified leisure activity participation and cognitive function. RESULTS: We observed bi-directorial associations between diversity of leisure activity and cognitive function across waves at the between-person and within-person levels. The adjusted random intercept cross-lagged panel models fitted the data appropriately, and the 3-year cross-lagged effects of prior diversified leisure activity participation on cognitive function (ß = 0.058, p < 0.01) and cognitive function on subsequent diversified leisure activity participation (ß = 0.047, p < 0.05) were significant. The results remained after adjusting the model for baseline sex, age, educational level, marital status and current residence, the number of chronic diseases, ADL, depressive symptoms, sleep quality, smoking, and drinking. CONCLUSION: This study suggests that a reciprocal causality relationship between diversified leisure activity participation and cognitive function, indicating a "positive circle" that further promotes cognition over time.

PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.

50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

The IFT80/Hedgehog Pathway Regulates the Osteogenic-adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated. OBJECTIVES: This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH. METHODS: Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression. RESULTS: RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation. CONCLUSION: There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.

Proteomic Analysis Reveals Trilaciclib-Induced Senescence.

Trilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukaemia (CML) cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilising CDK4/6 and downregulating cell cycle-related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the non-small cell lung carcinoma cell line (NSCLC), A549. These findings highlight trilaciclib's potential as a therapeutic option for haematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in CML treatment, as well as in NSCLC.

Synthesis and application of gelatin-based controlled-release antibacterial films containing oregano essential oil/ß-cyclodextrin microcapsules for chilling preservation of grass carp fillets.

This work aimed to synthesize oregano essential oil/ß-cyclodextrin microcapsules (OEO/ß-CDs) and then prepare gelatin-based controlled-release antibacterial films with different OEO/ß-CDs contents (0%-2%) for chilling preservation of grass carp fillets. The results of FTIR, XRD, DSC and accelerated release ratio showed that OEO was successfully encapsulated in OEO/ß-CDs and its thermal stability was effectively improved. Moreover, at 2% of addition amount of OEO/ß-CDs, the tensile strength of the films increased from 14.43 MPa to 18.72 MPa. In addition, the films showed significant antibacterial activity against Pseudomonas (61.52%), Aeromonas (62.87%), and Shewanella putrefaciens (66.67%). Preservation experiments showed that the films effectively prevented the increase of TVB-N, and TBA value of the refrigerated fillets and significantly suppressed the growth of spoilage organisms, thus extending the shelf life by 2-3 days. Therefore, the synthesized film has promising potential as an active packaging material for the preservation of grass carp.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

[Corrigendum] Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via PPARγ pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 1D on p. 1134, the data panels showing the results for the 'Control' and '1 µmol/l GW9662' experiments (on the left hand side of the figure) were overlapping, such that these data had been derived from the same original source where they were intended to show the results from differently performed experiments. The authors were able to re­examine their original data, and realize that the data for the '1 µmol/l GW9662' panel had been selected incorrectly. The corrected version of Fig. 1, now featuring the correct data for the '1 µmol/l GW9662' experiment in Fig. 1D, is shown on the next page, The authors confirm their error did not grossly affect either the results of the conclusions reported in the paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 1131-1140, 2015; DOI: 10.3892/ijo.2015.2829].

The Usage of Mesh and Relevant Prognosis in Implant Breast Reconstruction Surgery: A Meta-analysis.

BACKGROUND: Although mesh-based implant breast reconstruction surgery is emerging as the primary surgical procedure for breast reconstruction, mesh use remains controversial in implant breast reconstruction surgery, especially in terms of how to select the ideal mesh. Our aim is to elaborate relevant prognosis in the mesh-based implant breast reconstruction surgery. METHODS: Relevant studies were identified from PubMed, Web of Science, EMBASE, and Cochrane library searches. Extracted data included study type, basic characteristics, mesh information, complications, etc. We analyzed the included cohort studies and randomized controlled trials that reported mesh-related implant breast reconstruction complications and breast quality scale scores. RESULTS: A total of 32 studies including 7475 subjects were included. The results showed that the overall complication rate was 2.07 times higher in the biological mesh group than in the synthetic mesh group (risk ratio [RR]: 2.07, 95% CI 1.14-3.78). The risk of seroma was 4.50 times higher in the biological mesh group than in the synthetic mesh group (RR: 4.50, 95% CI 2.27-8.95). In terms of comparing breast quality scale scores, the mesh group had scores that were 1.49 (95% CI 0.19-2.78) higher than the non-mesh group for "physical well-being" and 2.05 (95% CI 0.08-4.02) higher for "sexual well-being." CONCLUSIONS: Our study found that the risk of total complications was higher with biological mesh than with synthetic mesh in implant breast reconstruction surgery. Based on short-term cost, healthcare burden, and healthcare benefits, synthetic meshes are superior to biological meshes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Thermoresponsive Gels with Embedded Starch Microspheres for Optimized Antibacterial and Hemostatic Properties.

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

Tungsten Inert Gas Welding of 6061-T6 Aluminum Alloy Frame: Finite Element Simulation and Experiment.

In order to address the irregularity of the welding path in aluminum alloy frame joints, this study conducted a numerical simulation of free-path welding. It focuses on the application of the TIG (tungsten inert gas) welding process in aluminum alloy welding, specifically at the intersecting line nodes of welded bicycle frames. The welding simulation was performed on a 6061-T6 aluminum alloy frame. Using a custom heat source subroutine written in Fortran language and integrated into the ABAQUS environment, a detailed numerical simulation study was conducted. The distribution of key fields during the welding process, such as temperature, equivalent stress, and post-weld deformation, were carefully analyzed. Building upon this analysis, the thin-walled TIG welding process was optimized using the response surface method, resulting in the identification of the best welding parameters: a welding current of 240 A, a welding voltage of 20 V, and a welding speed of 11 mm/s. These optimal parameters were successfully implemented in actual welding production, yielding excellent welding results in terms of forming quality. Through experimentation, it was confirmed that the welded parts were completely formed under the optimized process parameters and met the required product standards. Consequently, this research provides valuable theoretical and technical guidance for aluminum alloy bicycle frame welding.

Performance Prediction for Surgical Outcomes in Laparoscopic Partial Nephrectomy Using Nephrometry Scores: A Comparison of Zhongshan and Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location Systems.

Objective: The aim of this study is to compare the precision and applicability of the Zhongshan (ZS) score against the radius, exophytic/endophytic, nearness, anterior/posterior, and location (RENAL) score in forecasting perioperative outcomes during laparoscopic partial nephrectomy (LPN). Materials and Methods: We retrospectively analyzed data from 99 renal cancer patients who underwent LPN between January 2017 and August 2023. Patients were scored and categorized based on both the ZS and RENAL scores. The study then compared perioperative outcomes across these groups and further investigated the correlation between ZS and RENAL scores and overall complication rates. Results: LPN was successfully accomplished in 94 patients, whereas 5 patients necessitated conversion to open or radical surgery. The high-risk group, according to the ZS score, manifested more warm ischemic time (WIT) than the low-risk group (P = .007). Furthermore, the incidence of overall complications escalated with increase in the ZS score grade (P = .045). A higher RENAL score corresponded to a greater risk of conversion to open or radical treatment (P = .012). Correlation analyses revealed associations between both ZS and RENAL scores and overall complications. The RENAL score also correlated with changes in blood creatinine values, while the ZS score was associated with WIT (all P < .05). In the univariate analysis, both ZS and RENAL scores were substantial factors for the occurrence of total complications (P = .029 and P = .027, respectively), but they were not statistically significant in the multivariate analysis. The receiver operating characteristic curves suggested that both individual and combined ZS and RENAL scores held predictive potential for the onset of overall complications (area under the curve = 0.652, 0.660, and 0.676, respectively). Conclusions: Compared with the RENAL score, the ZS score provides a more comprehensive assessment of tumor complexity in patients undergoing LPN. Integrating these two scores could potentially improve the accuracy of predicting surgical risks.

Analysis of the contributing role of drug transport across biological barriers in the development and treatment of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) represents a major unmet medical need that currently has no preventive and/or curative treatment. This is, among others, driven by a poor understanding of the contributive role of drug transport across biological barriers to target-site exposure. METHODS: Here, we systematically investigated the transport of 11 small-molecule drugs, both, associated and not with CIPN development, at conventional (dorsal root ganglia, sciatic nerve) and non-conventional (brain, spinal cord, skeletal muscle) CIPN sites. We developed a Combinatory Mapping Approach for CIPN, CMA-CIPN, combining in vivo and in vitro elements. RESULTS: Using CMA-CIPN, we determined the unbound tissue-to-plasma concentration ratio (Kp,uu) and the unbound intracellular-to-extracellular concentration ratio (Kp,uu,cell), to quantitatively assess the extent of unbound drug transport across endothelial interfaces and parenchymal cellular barriers of investigated CIPN-sites, respectively, in a rat model. The analysis revealed that unique pharmacokinetic characteristics underly time-dependent accumulation of the CIPN-positive drugs paclitaxel and vincristine at conventional (dorsal root ganglia and sciatic nerve) and non-conventional (skeletal muscle) CIPN sites. Investigated CIPN-positive drugs displayed intracellular accumulation contrary to CIPN-negative drugs nilotinib and methotrexate, which lacked this feature in all investigated tissues. CONCLUSIONS: Hence, high unbound drug intracellular and extracellular exposure at target sites, driven by an interplay of drug transport across the endothelial and parenchymal cellular barriers, is a predisposing factor to CIPN development for CIPN-positive drugs. Critical drug-specific features of unbound drug disposition at various CIPN- sites provide invaluable insights into understanding the pharmacological/toxicological effects at the target-sites which will inform new strategies for monitoring and treatment of CIPN.

METnet: A novel deep learning model predicting MET dysregulation in non-small-cell lung cancer on computed tomography images.

BACKGROUND: Mesenchymal epithelial transformation (MET) is a key molecular target for diagnosis and treatment of non-small cell lung cancer (NSCLC). The corresponding molecularly targeted therapeutics have been approved by Food and Drug Administration (FDA), achieving promising results. However, current detection of MET dysregulation requires biopsy and gene sequencing, which is invasive, time-consuming and difficult to obtain tumor samples. METHODS: To address the above problems, we developed a noninvasive and convenient deep learning (DL) model based on Computed tomography (CT) imaging data for prediction of MET dysregulation. We introduced the unsupervised algorithm RK-net for automated image processing and utilized the MedSAM large model to achieve automated tissue segmentation. Based on the processed CT images, we developed a DL model (METnet). The model based on the grouped convolutional block. We evaluated the performance of the model over the internal test dataset using the area under the receiver operating characteristic curve (AUROC) and accuracy. We conducted subgroup analysis on the basis of clinical data of the lung cancer patients and compared the performance of the model in different subgroups. RESULTS: The model demonstrated a good discriminative ability over the internal test dataset. The accuracy of METnet was 0.746 with an AUC value of 0.793 (95% CI 0.714-0.871). The subgroup analysis revealed that the model exhibited similar performance across different subgroups. CONCLUSIONS: METnet realizes prediction of MET dysregulation in NSCLC, holding promise for guiding precise tumor diagnosis and treatment at the molecular level.

Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment.

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.

Secreted Clusterin Inhibits Tumorigenesis by Modulating Tumor Cell and Macrophage in Human Meningioma.

BACKGROUND: Meningioma is the most common primary intracranial tumor with high frequency of postoperative recurrence, yet the biology of meningioma malignancy process is still obscure. METHODS: To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at animal model and cellular level. RESULTS: Comprehensive analysis and validation in mice and clinical cohorts indicated Clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type I interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type I interferon pathway. The expression of CLU was upregulated by histone deacetylase inhibition. Meanwhile, both intra- and extra-cellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoted tumor killing and phagocytosis. CONCLUSIONS: CLU might be a key brake of meningioma malignance by synchronous modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.

Prognostic significance of LINC01132 in lung cancer and its regulatory role in tumor progression.

BACKGROUND: The application of long non-coding RNAs (lncRNAs) in cancer has been the focus of research in recent years. This study aimed to discuss the expression and functional mechanism of lncRNA LINC01132 (LINC01132) in lung cancer and explore its prognostic significance in tumors. METHODS: The expression of LINC01132 in lung cancer patients was verified using GSE98929 screening and real-time quantitative polymerase chain reaction (RT-qPCR) detection. The prognostic potential of LINC01132 was evaluated by performing the chi-square analysis of clinical indicators, Kaplan-Meier analysis, and Cox proportional hazard model. Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assay were used to characterize the biological functions of the lung cancer cells. The targeting relationship between LINC01132 and microRNA-125a-3p (miR-125a-3p), miR-125a-3p and SMAD2 was predicted by bioinformatics and verified by luciferase activity assay. RESULTS: LINC01132 was upregulated in lung cancer tissues and cells, which was an independent risk factor for survival and prognostic outcomes of lung cancer patients. Silencing LINC01132 suppressed the proliferation and migration of lung cancer cells and accelerated cell death. The target of LINC01132 was miR-125a-3p, and miR-125a-3p inhibitor could eliminate the inhibitory effect of LINC01132 knockdown on the cells. Additionally, SMAD2 is a downstream target of miR-125a-3p, and knockdown of SMAD2 reversed the effects of miR-125a-3p inhibitor on cell migration and invasion. CONCLUSION: LINC01132 may regulate the progression of lung cancer by targeting the miR-125a-3p /SMAD2 axis and serve as a prognostic biomarker for lung cancer.

Differentiation Potential of Hypodifferentiated Subsets of Nephrogenic Rests and Its Relationship to Prognosis in Wilms Tumor.

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.