Dual Oxygen-Supply Immunosuppression-Inhibiting Nanomedicine to Avoid the Intratumoral Recruitment of Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft.

Nanofiber-reinforced chitosan/gelatine hydrogel with photothermal, antioxidant and conductive capabilities promotes healing of infected wounds.

The wound healing process was often accompanied by bacterial infection and inflammation. The combination of electrically conductive nanomaterials and wound dressings could accelerate cell proliferation through endogenous electrical signaling, effectively promoting wound healing. In this study, polypyrrole was modified with dopamine hydrochloride by an in situ polymerization to form dopamine-polypyrrole (DA-Ppy) conductive nanofibers which successfully enhanced the water dispersibility and biocompatibility of polypyrrole. The DA-Ppy nanofibers were dispersed in an aqueous solution for >48 h and still maintained good stability. In addition, the DA-Ppy nanofibers showed good photothermal properties, and the temperature could reach 59.7 °C by 1.5 W/cm2 near-infrared light irradiation (NIR) for 10 min. DA-Ppy conductive nanofibres could be well dispersed in 3,4-dihydroxyphenylpropionic acid modified chitosan-carboxymethylated ß-cyclodextrin modified gelatin (CG) hydrogel due to the presence of DA, which endowed CG/DA-Ppy hydrogel with good adhesion properties, and the hydrogel adhered to the pigskin would not be dislodged by washing with running water. Under NIR, the CG/DA-Ppy hydrogel showed significant antimicrobial properties. Moreover, the CG/DA-Ppy hydrogel had excellent biocompatibility. In addition, CG/DA-Ppy hydrogel was effective in scavenging ROS, inducing macrophage polarization towards the M2 phenotype, and modulating the level of wound inflammation in vitro. Finally, it was confirmed in rat-infected wounds that the tissue regeneration effect and collagen deposition in the CG/DA-Ppy + NIR group were significantly better than the other groups in the repair of infected wounds, indicating better repair of infected wounds. The results suggested that the photothermal, antioxidant DA-Ppy conductive nanofiber had great potential for application in infected wound healing.

A novel tetrahedral framework nucleic acid-derived chemodynamic therapy agent for effective glioblastoma treatment.

Chemodynamic therapy (CDT) has garnered significant attention for treating diverse malignant tumours due to its minimally invasive nature, reduced damage to healthy tissues, and potential mitigation of side effects. However, its application in glioblastoma (GBM) is hindered by the diminished capacity of CDT agents to traverse the blood-brain barrier (BBB), inadequate tumour targeting efficiency, and restricted availability of H2O2 within the tumour microenvironment (TME). To address these challenges, we devised a novel CDT agent (Fe@tFNAs-ANG-3AT) based on a tetrahedral framework nucleic acids (tFNAs). Fe@tFNAs-ANG-3AT was constructed by anchoring iron ions (Fe3+) onto the dual appendages-modified tFNAs. Specifically, one appendage, Angiopep-2 (ANG, a penetrating peptide), facilitates Fe@tFNAs-ANG-3AT penetration across the BBB and selective targeting of tumour cells. Simultaneously, the second appendage, 3-Amino-1,2,4-triazole (3AT, a H2O2 enzyme inhibitor), augments the H2O2 levels required for effective CDT treatment. Upon tumour cell internalization, the loaded Fe3+ in Fe@tFNAs-ANG-3AT is reduced to Fe2+ by the overexpressed glutathione (GSH) in the TME, catalysing the generation of cytotoxic hydroxyl radicals (·OH) and inducing tumour cell death via elevated oxidative stress levels within tumour cells. It is anticipated that Fe@tFNAs-ANG-3AT holds promise as a transformative treatment strategy for GBM.

Computational biomechanics for a standing human body: Modal analysis and simulation.

We develop computational mechanical modeling and methods for the analysis and simulation of the motions of a human body. This type of work is crucial in many aspects of human life, ranging from comfort in riding, the motion of aged persons, sports performance and injuries, and many ergonomic issues. A prevailing approach for human motion studies is through lumped parameter models containing discrete masses for the parts of the human body with empirically determined spring, mass, damping coefficients. Such models have been effective to some extent; however, a much more faithful modeling method is to model the human body as it is, namely, as a continuum. We present this approach, and for comparison, we choose two digital CAD models of mannequins for a standing human body, one from the versatile software package LS-DYNA and another from open resources with some of our own adaptations. Our basic view in this paper is to regard human motion as a perturbation and vibration from an equilibrium position which is upright standing. A linear elastodynamic model is chosen for modal analysis, but a full nonlinear viscoelastoplastic extension is possible for full-body simulation. The motion and vibration of these two mannequin models is analyzed by modal analysis, where the normal vibration modes are determined. LS-DYNA is used as the supercomputing and simulation platform. Four sets of low-frequency modes are tabulated, discussed, visualized, and compared. Higher frequency modes are also selectively displayed. We have found that these modes of motion and vibration form intrinsic basic modes of biomechanical motion of the human body. This view is supported by our finding of the upright walking motion as a low-frequency mode in modal analysis. Such a "walking mode" shows the in-phase and out-of-phase movements between the legs and arms on the left and right sides of a human body, implying that this walking motion is spontaneous, likely not requiring any directives from the brain. Dynamic motions of CAD mannequins are also simulated by drop tests for comparisons and the validity of the models is discussed through Fourier frequency analysis. All computed modes of motion are collected in several sets of video animations for ease of visualization. Samples of LS-DYNA computer codes are also included for possible use by other researchers.

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence.

Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in a translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that the dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.

Causal Relationship between Mitochondrial-Associated Proteins and Sepsis in ICU Patients: A Mendelian Randomization Study.

BACKGROUND: The alarming mortality rate of sepsis in ICUs has garnered significant attention. The precise etiology remains elusive. Mitochondria, often referred to as the cellular powerhouses, have been postulated to have a dysfunctional role, correlating with the onset and progression of sepsis. However, the exact causal relationship remains to be defined. METHOD: Employing the Mendelian randomization approach, this study systematically analyzed data from the IEUOpenGWAS and UKbiobank databases concerning mitochondrial function-related proteins and their association with sepsis, aiming to delineate the causal relationship between the two. RESULTS: The findings underscored a statistically significant association of GrpE1 with sepsis, registering a P value of 0.005 and an OR of 0.499 (95% CI: 0.307-0.810). Likewise, HTRA2, ISCU, and CUP3 each manifested significant associations with sepsis, yielding OR values of 0.585, 0.637, and 0.634, respectively. These results suggest potential implications of the aforementioned proteins in the pathogenesis of sepsis. CONCLUSION: The present study furnishes novel evidence elucidating the roles of GrpE1, HTRA2, ISCU, and CUP3 in the pathophysiology of sepsis. Such insights pave the way for a deeper understanding of the pathological mechanisms underpinning sepsis and hint at promising therapeutic strategies for the future.

Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 µM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

Causal associations of gut microbiota and metabolites on sepsis: a two-sample Mendelian randomization study.

Background: Sepsis stands as a dire medical condition, arising when the body's immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora's known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span. Methods: Leveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium. Results: In this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029). Conclusion: This research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis' pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis' diagnosis, therapeutic interventions, and prognostic assessments.

HybriSeq: Probe-based Device-free Single-cell RNA Profiling.

We have developed the HybriSeq method for single-cell RNA profiling, which utilizes in situ hybridization of multiple probes for targeted transcripts, followed by split-pool barcoding and sequencing analysis of the probes. We have shown that HybriSeq can achieve high sensitivity for RNA detection with multiple probes and profile RNA accessibility. The utility of HybriSeq is demonstrated in characterizing cell-to-cell heterogeneities of a panel of 95 cell-cycle-related genes and the probe-probe heterogeneity within a single transcript.

Assessing pharmacogenomic literacy in China through validation of the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy.

Pharmacogenomics (PGx) implementation into clinical care is rapidly increasing in China. However, the extent to which the public understands PGx testing and important knowledge domains requiring patient education or counseling remains unclear. To address this, we created and validated the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL-CTM ). The MAPL-C was developed by translating the English MAPL to Chinese following cross-cultural translation guidelines. An online survey validated the MAPL-C and assessed Chinese individuals' PGx literacy. Validation analyses were performed and associations of PGx literacy with participants' characteristics were quantified. Of 959 high-quality responses, the majority of respondents were Han Chinese (96.3%), men (54.5%), aged 18-29 years (70.9%), residing in China (97.3%), and had received college or higher education (95.0%). Out of 15 starting items developed to query specific predefined knowledge domains, two uninformative items were excluded, resulting in a 13-item MAPL-C. Chinese participants' MAPL-C performance was best explained by a three-factor model, encompassing PGx concepts and function, testing limitations, and privacy. Higher MAPL-C performance was associated with younger age, higher education, and previous genetic testing experience. Correct response rates for questions related to testing limitations were lower than those in other domains. The creation and validation of the MAPL-C fills a gap in determining PGx knowledge among Chinese speakers, quantifying PGx literacy within a Chinese cohort, and identifying response patterns and knowledge gaps. The MAPL-C can be useful in clinical practice to guide patient counseling, assess PGx education interventions, and quantify PGx knowledge in relation to outcomes in research studies involving Chinese participants.

Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure.

Acute liver failure (ALF) is characterized by rapid liver cell destruction. It is a multi-etiological and fulminant complication with a clinical mortality of over 80%. Therapy using mesenchymal stem cells (MSCs) or MSCs-derived exosomes can alleviate acute liver injury, which has been demonstrated in animal experiments and clinical application. However, similar to other stem cells, different cell sources, poor stability, cell senescence and other factors limit the clinical application of MSCs. To achieve mass production and quality control on stem cells and their exosomes, transfecting umbilical cord mesenchymal stem cell (UCMSC) with lentivirus overexpressing human telomerase reverse transcriptase (hTERT) gene, the hTERT-UCMSC was constructed as an immortalized MSC cell line. Compared with the primary UCMSC (P3) and immortalized cell line hTERT-UCMSC at early passage (P10), the hTERT-UCMSC retained the key morphological and physiological characteristics of UCMSC at the 35th passage (P35), and showed no signs of carcinogenicity and toxic effect in mice. There was no difference in either exosome production or characteristics of exosomes among cultures from P3 primary cells, P10 and P35 immortalized hTERT-UCMSCs. Inoculation of either hTERT-UCMSC (P35) or its exosomes improved the survival rate and liver function of ALF mice induced by thioacetamide (TAA). Our findings suggest that this immortalized cell line can maintain its characteristics in long-term culture. Inoculation of hTERT-UCMSC and its exosomes could potentially be used in clinics for the treatment of liver failure in the future.

Thalamic network under wakefulness after sleep onset and its coupling with daytime fatigue in insomnia disorder: An EEG-fMRI study.

BACKGROUND: Fatigue is the most common daytime impairment of insomnia disorder (ID). Thalamus is acknowledged as the key brain region closely associated with fatigue. However, the thalamus-based neurobiological mechanisms of fatigue in patients with ID remain unknown. METHODS: Forty-two ID patients and twenty-eight well-matched healthy controls (HCs) underwent simultaneous electroencephalography--functional magnetic resonance imaging. We calculated the functional connectivity (FC) between the thalamic seed and each voxel across the whole brain in two conditions of wakefulness--after sleep onset (WASO) and before sleep onset. A linear mixed effect model was used to determine the condition effect of the thalamic FC. The correlation between daytime fatigue and the thalamic connectivity was explored. RESULTS: After sleep onset, the connectivity with the bilateral thalamus was increased in the cerebellar and cortical regions. Compared with HCs, ID patients showed significantly lower FC between left thalamus and left cerebellum under the WASO condition. Furthermore, thalamic connectivity with cerebellum under the WASO condition was negatively correlated with Fatigue Severity Scale scores in the pooled sample. CONCLUSIONS: These findings contribute to an emerging framework that reveals the link between insomnia-related daytime fatigue and the altered thalamic network after sleep onset, further highlighting the possibility that this neural pathway is a therapeutic target for meaningfully mitigating fatigue.

Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton's jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2-related factor 2 signaling. CONCLUSION: These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

Increased connectivity of the anterior cingulate cortex is associated with the tendency to awakening during N2 sleep in patients with insomnia disorder.

STUDY OBJECTIVES: To investigate the relationship between sleep transition dynamics and stage-specific functional connectivity (FC) of the anterior cingulate cortex (ACC) in patients with insomnia disorder (ID). METHODS: Simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data from 37 patients with ID and 30 well-matched healthy controls (HCs) were recorded during wakefulness and different sleep stages and subsequently analyzed. A Markov chain model was used to estimate the transition probability between each stage. The FC between the ACC (set as the seed) and voxels across the whole brain was calculated. A linear mixed effect model was used to determine the group-by-stage interaction of the seed-based connectivity. The correlation between the sleep-stage transition probability and the ACC-based connectivity was explored. RESULTS: Patients with ID exhibited a higher likelihood of transitioning from N2 to wakefulness than HCs. A significant group-by-stage interaction of connectivity with the bilateral ACC was observed in the cerebellar, subcortical, and cortical regions. Moreover, a significant positive correlation was found in patients with ID between the transition probability from N2 to wakefulness and the FC of the ACC with the anterior cerebellum in N2 (r = 0.48). CONCLUSIONS: This exploratory analysis indicates that enhanced FC between the ACC and cerebellum represents a potential neural pathway underlying the greater likelihood of patients with ID waking during N2 sleep. These findings contribute to an emerging framework that reveals the link between sleep maintenance difficulty and ACC function, further highlighting the possibility that N2 sleep is a therapeutic target for meaningfully reducing sleep disruption.

State-dependent and region-specific alterations of cerebellar connectivity across stable human wakefulness and NREM sleep states.

Sleep regulation and functioning may rely on systematic coordination throughout the whole brain, including the cerebellum. However, whether and how interactions between the cerebellum and other brain regions vary across sleep stages remain poorly understood. Here, using simultaneous EEG-fMRI recordings captured from 73 participants during wakefulness and non-rapid eye movement (NREM) sleep, we constructed cerebellar connectivity among intrinsic functional networks with intra-cerebellar, neocortical and subcortical regions. We uncovered that cerebellar connectivity exhibited sleep-dependent alterations: slight differences between wakefulness and N1/N2 sleep and greater changes in N3 sleep than other states. Region-specific cerebellar connectivity changes between N2 sleep and N3 sleep were also revealed: general breakdown of intra-cerebellar connectivity, enhancement of limbic-cerebellar connectivity and alterations of cerebellar connectivity with spatially specific neocortices. Further correlation analysis showed that functional connectivity between the cerebellar Control II network and regions (including the insula, hippocampus, and amygdala) correlated with delta power during N3 and beta power during N2 sleep. These findings systematically reveal altered cerebellar connectivity among intrinsic networks from wakefulness to deep sleep and highlight the potential role of the cerebellum in sleep regulation and functioning.

Sleep discrepancy is associated with alterations in the salience network in patients with insomnia disorder: An EEG-fMRI study.

BACKGROUND: Positron emission tomography - computed tomography (PET-CT) research has shown that sleep discrepancy recorded by self-report and polysomnography (PSG) may be related to the altered metabolic rate of the anterior insula (aINS) during non-rapid eye movement (NREM) sleep in patients with insomnia disorder. We aim to explore the functional connectivity of aINS across wake and NREM sleep in the patients and to reveal the association between aINS connectivity and sleep discrepancy. METHODS: Patients with insomnia disorder (n = 33) and healthy controls (n = 31) underwent simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) during nighttime sleep, and aINS-based connectivity was calculated across wake and NREM sleep. A linear mixed-effects model was used to assess the main effect of group and group-by-stage (wake, NREM stages 1-3) interaction effect on aINS connectivity. Similar mixed models were used to assess the potential correlation between aINS connectivity and the sleep misperception index (MI). RESULTS: A significant group-by-stage interaction effect on aINS-based connectivity was observed in the bilateral frontal gyrus, right inferior temporal gyrus, bilateral middle occipital gyrus and right postcentral gyrus (p < 0.05, corrected). There was also a significant group-by-MI interaction effect on aINS connectivity with the putamen and thalamus during wakefulness (p < 0.05 corrected); MI was significantly associated with aINS-putamen/thalamus connectivity in the control group, whereas the association was weak or even nonsignificant in the patient group. There was no significant main effect of group. CONCLUSION: The waking activity of a neural pathway containing the aINS, putamen, and thalamus may underlie sleep perception, potentially providing important perspectives to reveal complex mechanisms of sleep discrepancy between self-report and PSG.

Application of 3D Hepatic Plate-Like Liver Model for Statin-Induced Hepatotoxicity Evaluation.

Background: Drug-induced liver injury is one of the main reasons of withdrawals of drugs in postmarketing stages. However, an experimental model(s) which can accurately recapitulates liver functions and reflects the level of drug hepatotoxicity is lack. In this study, we assessed drug hepatotoxicity using a novel three-dimensional hepatic plate-like hydrogel fiber (3D-P) co-culture system. Methods: During the 28-days culture period, the liver-specific functions, hepatocyte polarity, sensitivity of drug-induced toxicity of 3D-P co-culture system were evaluated with 2D co-culture, collagen sandwich co-culture, 3D hybrid hydrogel fiber co-culture and human primary hepatocytes as controls. High-content imaging and analysis (HCA) methods were used to explore the hepatotoxicity mechanism of five statins. Results: The 3D-P co-culture system showed enhancing liver-specific functions, cytochrome P450 enzymes (CYPs) metabolic activity and bile excretion, which were considered to result from improved hepatocyte polarity. Three of the statins may cause acute or chronic hepatotoxicity by via different mechanisms, such as cholestatic liver injury. Conclusion: Our 3D-P co-culture system is characterized by its biomimetic hepatic plate-like structure, long-term stable liver specificity, and prominent bile secretion function, making it applicable for acute/chronic drug hepatotoxicity assessments.

Development and validation of an MRI-based nomogram for the preoperative prediction of tumor mutational burden in lower-grade gliomas.

Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors. In this study, we aimed to determine the value of magnetic resonance (MR)-based preoperative nomogram in predicting TMB status in lower-grade glioma (LGG) patients. Methods: Overall survival (OS) data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by using the Kaplan-Meier method and time-dependent receiver operating characteristic (tdROC) analysis. The magnetic resonance imaging (MRI) data of 168 subjects obtained from The Cancer Imaging Archive (TCIA) were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analyses. Finally, we performed tenfold cross validation. TMB values were retrieved from the supplementary information of a previously published article. Results: The high TMB subtype was associated with the shortest median OS (high vs. low: 50.9 vs. 95.6 months, P<0.05). The tdROC for the high-TMB tumors was 74% (95% CI: 61-86%) for survival at 12 months, and 71% (95% CI: 60-82%) for survival at 24 months. Multivariate logistic regression analysis confirmed that three risk factors [extranodular growth: odds ratio (OR): 8.367, 95% CI: 3.153-22.199, P<0.01; length-width ratio ≥ median: OR: 1.947, 95% CI: 1.025-3.697, P<0.05; frontal lobe: OR: 0.455, 95% CI: 0.229-0.903, P<0.05] were significant independent predictors of high-TMB tumors. The nomogram showed good calibration and discrimination. This model had an area under the curve (AUC) of 0.736 (95% CI: 0.655-0.817). Decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. The average accuracy of the tenfold cross validation was 71.6% for high-TMB tumors. Conclusions: Our results indicated that a distinct OS disadvantage was associated with the high TMB group. In addition, extranodular growth, nonfrontal lobe tumors and length-width ratio ≥ median can be conveniently used to facilitate the prediction of high-TMB tumors.