Bi-Pt Heterojunction Cascade Reaction Platform for Sono-Immunotherapy of Tumors via PANoptosis and Ferroptosis.

Sonodynamic therapy (SDT) represents a promising, noninvasive, and precise treatment modality for tumors, demonstrating significant potential in clinical applications. However, the efficiency of sonosensitizers in generating reactive oxygen species (ROS) is often limited by rapid electron-hole recombination. In this study, BiF3@BiOI is synthesized via a co-precipitation method, followed by in-situ reduction to decorate it with Pt nanoparticles, resulting in BiF3@BiOI@Pt-PVP (BBP) nanocomposite for enhancing SDT efficacy. The formation of the BiF3@BiOI heterojunction enhances charge separation ability. The decoration of Pt nanoparticles narrows the bandgap and alters the band positions and Fermi level of BBP, which can effectively mitigate the rapid recombination of electron-hole pairs and facilitate a cascade reaction of ROS, thereby improving ROS generation efficiency with ultrasound excitation. Additionally, bismuth ions in BBP and the generated holes consume glutathione, exacerbating cellular oxidative damage, and triggering PANoptosis and ferroptosis. Furthermore, Pt nanoparticles demonstrate peroxidase-like activity, catalyzing endogenous hydrogen peroxide to oxygen. These functions are helpful against tumors for alleviating hypoxic conditions, reshaping the microenvironment, modulating immune cell infiltration capacity, and enhancing the efficacy of immunotherapy. The dual strategy of forming heterojunctions and sensitization with noble metals effectively enhances the efficacy of sono-catalytic therapy-induced immune activation in tumor treatment.

Engineering the nanozyme hydrogel beads by polyvinyl alcohol/chitosan encapsulation with recyclable and sustainable catalytic activity for visual analysis of hydrogen peroxide.

BACKGROUND: Hydrogen peroxide (H2O2) plays a vital role in human health and have been regarded as a crucial analyte in metabolic processes, redox transformations, foods research and medical fields. Especially, the long-time and excessive digestion of H2O2 may even cause severe diseases. Although conventional instrumental methods and nanozymes-based colorimetric methods have been developed to accomplish the quantitative analysis of H2O2, the drawbacks of instrument dependence, cost-effectiveness, short lifespan, non-portable and unsustainable detection efficacies will limit their applications in different detection scenarios. RESULTS: Herein, to address these challenges, we have proposed a novel strategy for nanozyme (RuO2) hydrogel preparation by the solid support from cross-linked polyvinyl alcohol (PVA) and chitosan (CS) to both inherit the dominant peroxidase-like (POD) activity and protect the RuO2 from losing efficacies. Taking advantages from the hydrogel, the encapsulated RuO2 were further prepared as the regularly spherical beads (PCRO) to exhibit the sustainable, recyclable, and robust catalysis. Moreover, the intrinsic color interferences which originated from RuO2 can be avoided by the encapsulation strategy to promote the detection accuracy. Meanwhile, the high mechanical strength of PCRO shows the high stability, reproducibility, and cyclic catalysis to achieve the recyclable detection performance and long lifetime storage (40 days), which enables the sensitively detection of H2O2 with the detection limit as lower to 15 µM and the wide detection linear range from 0.025 to 1.0 mM. SIGNIFICANCE: On the basis of the unique properties, PCRO has been further adopted to construct a smartphone detection platform to realize the instrument-free and visual analysis of H2O2 in multi-types of milk and real water samples through capturing, processing, and analyzing the RGB values from the colorimetric photographs. Therefore, PCRO with the advanced detection efficacies holds the great potential in achieving the portable and on-site analysis of targets-of-interest.

A Low Mismatch Current Charge Pump Applied to Phase-Locked Loops.

This paper presents a charge pump circuit with a wide output range and low current mismatch applied to phase-locked loops. In this designed structure, T-shaped analog switches are adopted to suppress the non-ideal effects of clock feedthrough, switching time mismatch, and charge injection. A source follower and current splitting circuits are proposed to improve the matching accuracy of the charging and discharging currents and reduce the current mismatch rate. A rail-to-rail high-gain amplifier with a negative feedback connection is introduced to suppress the charge-sharing effect of the charge pump. A cascode current mirror with a high output impedance is used to provide the charge and discharge currents for the charge pump, which not only improves the current accuracy of the charge pump but also increases the output voltage range. The proposed charge pump is designed and simulated based on a 65 nm CMOS process. The results show that when the power supply voltage is 1.2 V, the output current of the charge pump is 100 µA, the output voltage is in the range of 0.2~1 V, and the maximum current mismatch rate and current variation rate are only 0.21% and 1.4%, respectively.

Recreational gymnastics exercise of moderate intensity enhances executive function in Chinese preschoolers: A randomized controlled trial.

The current study aimed to investigate the impact of recreational gymnastics on executive function in Chinese preschoolers, with a focus on gymnastics potential to enhance core components of executive function. A total of 63 preschool children who received full-time education were randomly assigned to either an intervention group (N = 31, mean age = 66.27 months, SD = 3.12 months) or a control group (N = 32, mean age = 66.79 months, SD = 3.34 months). The intervention group engaged in recreational gymnastics for 60 min, three times a week for 12 weeks. Meanwhile, the control group continued with their typical outdoor activities at kindergarten and did not participate in any organized sports. The intervention program was primarily conducted through group play and was facilitated by teachers who underwent standardized training. Various simple and complex tasks were utilized to evaluate delay gratification (Snack delay and Wrapped gift), inhibitory control (Stop signal task and Circle drawing task), working memory (Letter memory task and Keep track task), and cognitive flexibility (Go/No-Go task and Dots task). The analysis of covariance revealed that the children who participated in the intervention outperformed the control group on most simple and complex executive function tasks. Specifically, these children demonstrated an enhanced ability to regulate persistent responses, process and update information, and manage high cognitive conflict. The findings of this investigation lend support to the hypothesis that moderate-intensity recreational gymnastics is an efficacious means of enhancing executive function in early childhood. Future research should employ a larger sample size, incorporate a long-term follow-up design, and utilize a multi-method approach to further substantiate the impact of moderate-intensity gymnastics on the executive function of young children, as well as to investigate its underlying mechanism and generalizability.

Deubiquitinase PSMD14 promotes tumorigenicity of glioblastoma by deubiquitinating and stabilizing ß-catenin.

The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a member of the JAB1/MPN/Mov34 metalloenzyme (JAMM) family, has been shown to function as an oncogene in various human cancers. However, the function of PSMD14 in glioma and the underlying mechanism remain unclear. In this study, our findings reveal a dramatic upregulation of PSMD14 in GBMs, which is associated with poor survival outcomes. Knocking down PSMD14 is associated with decreased proliferation and invasion of GBM cells in vitro and inhibited tumor growth in a xenograft mouse model. Mechanistically, PSMD14 directly interacts with ß-catenin, leading to a decrease in the K48-linked ubiquitination of ß-catenin and subsequent ß-catenin stabilization. Increased ß-catenin expression significantly reverses the inhibitory effects of PSMD14 knockdown on the migration, invasion, and tumor growth of GBM cells. Moreover, we observed a significant correlation between PSMD14 and ß-catenin expression in human GBM samples. In summary, our results reveal that PSMD14 is a crucial deubiquitinase that is responsible for stabilizing the ß-catenin protein, highlighting its potential for use as a therapeutic target for GBM.

Cuproptosis: Advances in Stimulus-Responsive Nanomaterials for Cancer Therapy.

Cuproptosis, a recently identified non-apoptotic programmed cell death modality, attracts considerable attention in the realm of cancer therapeutics owing to its unique cellular demise mechanisms. Since its initial report in 2022, strategies inducing or amplifying cuproptosis for cancer treatment emerge. The engineering of nano-systems to elicit cuproptosis effectively circumvents constraints associated with conventional small-molecule pharmaceutical interventions, presenting novel prospects for oncological therapy. Stimulus-responsive nanomaterials, leveraging their distinctive spatiotemporal control attributes, are investigated for their role in modulating the induction or augmentation of cuproptosis. In this comprehensive review, the physiological characteristics of cuproptosis, encompassing facets such as copper overload and depletion, coupled with regulatory factors intrinsic to cuproptosis, are expounded upon. Subsequently, design methodologies for stimulus-responsive induction or enhancement of cuproptosis, employing stimuli such as light, ultrasound, X-ray, and the tumor microenvironment, are systematically delineated. This review encompasses intricacies in nanomaterial design, insights into the therapeutic processes, and the associated advantages. Finally, challenges inherent in stimulus-responsive induction/enhancement of cuproptosis are deliberated upon and prospective insights into the future trajectory of copper-mediated cancer therapy are provided.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

High-Z elements dominated bismuth-based heterojunction nano-semiconductor for radiotherapy-enhanced sonodynamic breast cancer therapy.

Ultrasound and X-rays possess remarkable tissue penetration capabilities, making them promising candidates for cancer therapy. Sonodynamic therapy, which utilizes ultrasound excitation, offers a safer alternative to radiotherapy and can be combined with X-rays to mitigate the adverse effects on normal tissues. In this study, we developed a bismuth-based heterostructure semiconductor (BFIP) to enhance the efficacy of radiotherapy and sonodynamic therapy in treating breast cancer. The semiconductor is fabricated through a two-step process involving the synthesis of porous spherical bismuth fluoride and partially reduced to bismuth oxyiodide. Then, followed by surface modification with amphiphilic polyethylene glycol, BFIP is fabricated. Incorporating heavy atoms in the BFIP enhances radiosensitivity. The BFIP exhibits superior carrier separation efficiency compared to bismuth fluoride, generating a substantial quantity of reactive oxygen species upon ultrasound stimulation. Moreover, the BFIP effectively depletes glutathione through coordination and hole-mediated oxidation pathways, disrupting the tumor microenvironment and inducing oxidative stress. Encouraging results are acquired in both in vitro cell and in vivo tumor models. Our study provides a de-risking strategy by utilizing ultrasound as a partial substitute for X-rays in treating deep-seated tumors, offering a viable research direction for constructing a unified nanoplatform.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

A ratiometric radio-photoluminescence dosimeter based on a radical excimer for X-ray detection.

A novel radio-photoluminescence material featuring fluorochromic responses toward UV or X-ray irradiation has been obtained. Such a unique monomer- to excimer-based luminescence transition allows for dosimetry of ionizing radiation in a ratiometric manner. Rather than quenching the luminescence, the radiation-induced radical species of Th-105 boost the excimer emission, rendering it as a rare material possessing radical-excimers.

Single-cell sequencing analysis of peripheral blood in patients with moyamoya disease.

BACKGROUND: At present, the etiology of moyamoya disease is not clear, and it is necessary to explore the mechanism of its occurrence and development. Although some bulk sequencing data have previously revealed transcriptomic changes in Moyamoya disease, single-cell sequencing data has been lacking. METHODS: Two DSA(Digital Subtraction Angiography)-diagnosed patients with moyamoya disease were recruited between January 2021 and December 2021. Their peripheral blood samples were single-cell sequenced. CellRanger(10 x Genomics, version 3.0.1) was used to process the raw data, demultiplex cellular barcodes, map reads to the transcriptome, and dowm-sample reads(as required to generate normalized aggregate data across samples). There were 4 normal control samples, including two normal samples GSM5160432 and GSM5160434 of GSE168732, and two normal samples of GSE155698, namely GSM4710726 and GSM4710727. Weighted co-expression network analysis was used to explore the gene sets associated with moyamoya disease. GO analysis and KEGG analysis were used to explore gene enrichment pathways. Pseudo-time series analysis and cell interaction analysis were used to explore cell differentiation and cell interaction. RESULTS: For the first time, we present a peripheral blood single cell sequencing landscape of Moyamoya disease, revealing cellular heterogeneity and gene expression heterogeneity. In addition, by combining with WGCNA analysis in public database and taking intersection, the key genes in moyamoya disease were obtained. namely PTP4A1, SPINT2, CSTB, PLA2G16, GPX1, HN1, LGALS3BP, IFI6, NDRG1, GOLGA2, LGALS3. Moreover, pseudo-time series analysis and cell interaction analysis revealed the differentiation of immune cells and the relationship between immune cells in Moyamoya disease. CONCLUSIONS: Our study can provide information for the diagnosis and treatment of moyamoya disease.

Liquid-liquid phase separation-related gene in gliomas: FABP5 is a potential prognostic marker.

BACKGROUND: The glioma is the most malignant human brain tumor. Early glioma detection and treatment are still difficult. New biomarkers are desperately required to aid in the evaluation of diagnosis and prognosis. METHODS: The single cell sequencing dataset scRNA-6148 for glioblastoma was obtained from the Chinese Glioma Genome Atlas database. Data were gathered for the transcriptome sequencing project. Genes involved in liquid-liquid phase separation (LLPS) were taken out of the DrLLPS database. To find the modules connected to LLPS, the weighted co-expression network was analyzed. Differential expression analysis was used to identify the differentially expressed genes (DEGs) in gliomas. Pseudo-time series analysis, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were used to investigate the role of important genes in the immunological microenvironment. We examined the function of key glioma genes using polymerase chain reaction (PCR) testing, CCK-8 assays, clone generation assays, transwell assays and wound healing assays. RESULTS: FABP5 was identified as a key gene in glioblastoma by multiomics research. Pseudo-time series analysis showed that FABP5 was highly linked with the differentiation of many different types of cells. GSEA revealed that FABP5 was strongly linked to several hallmark pathways in glioblastoma. We looked at immune cell infiltration and discovered a significant link between FABP5, macrophages and T cell follicular helpers. The PCR experiment results demonstrated that FABP5 expression was elevated in glioma samples. Cell experiments showed that FABP5 knockdown dramatically decreased the viability, proliferation, invasion and migration of the LN229 and U87 glioma cell lines. CONCLUSIONS: Our study provides a new biomarker, FABP5, for glioma diagnosis and treatment.

Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study.

Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m2) on Days 1 and 8 and oxaliplatin (85 mg/m2) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825).Trial registration Clinical trials: NCT03951597.

Loss of 5-hydroxymethylcytosine induces chemotherapy resistance in hepatocellular carcinoma via the 5-hmC/PCAF/AKT axis.

Multidrug resistance is a major challenge in treating advanced hepatocellular carcinoma (HCC). Although recent studies have reported that the multidrug resistance phenotype is associated with abnormal DNA methylation in cancer cells, the epigenetic mechanism underlying multidrug resistance remains unknown. Here, we reported that the level of 5-hydroxymethylcytosine (5-hmC) in human HCC tissues was significantly lower than that in adjacent liver tissues, and reduced 5-hmC significantly correlated with malignant phenotypes, including poor differentiation and microvascular invasion; additionally, loss of 5-hmC was related to chemotherapy resistance in post-transplantation HCC patients. Further, the 5-hmC level was regulated by ten-eleven translocation 2 (TET2), and the reduction of TET2 in HCC contributes to chemotherapy resistance through histone acetyltransferase P300/CBP-associated factor (PCAF) inhibition and AKT signaling hyperactivation. In conclusion, loss of 5-hmC induces chemotherapy resistance through PCAF/AKT axis and is a promising chemosensitivity prediction biomarker and therapeutic target for HCC patients.

The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

Intratumor microbiome features reveal antitumor potentials of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with a high prevalence in China. This study aimed to characterize the ICC tissues' bacterial metagenomics signature and explore its antitumor potential for cancer. In this study, 16S rRNA sequencing was carried out on 99 tissues to characterize the features of intratumoral microbiota, followed by single-cell RNA sequencing (scRNA-seq) and multilevel validation. The presence of microbial DNA in tissues was determined using staining, fluorescence in situ hybridization (FISH), and transmission electron microscopy (TEM). A Gram-positive aerobic bacterium, identified as Staphylococcus capitis, was cultured from fresh tissues. Meanwhile, scRNA-seq showed that intratumoral bacteria could be present in multiple cell types. Using 16S rRNA sequencing, we identified a total of 2,320,287 high-quality reads corresponding to 4,594 OTU (operational taxonomic units) sequences. The most abundant bacterial orders include Burkholderiales, Pseudomonadales, Xanthomonadales, Bacillales and Clostridiales. Alpha and Beta diversity analysis revealed specific features in different tissues. In addition, the content of Paraburkholderia fungorum was significantly higher in the paracancerous tissues and negatively correlated with CA199 (Carbohydrate antigen199) levels. The results of in vitro and in vivo experiments suggest that P. fungorum possesses an antitumor activity against tumors. Metabolomics and transcriptomics showed that P. fungorum could inhibit tumor growth through alanine, aspartate and glutamate metabolism. We determined the characteristic profile of the intratumoral microbiota and the antitumor effect of P. fungorum in ICC.

USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1.

Recent studies suggest that Forkhead box D1 (FOXD1) plays an indispensable role in maintaining the mesenchymal (MES) properties of glioblastoma (GBM) stem cells (GSCs). Thus, understanding the mechanisms that control FOXD1 protein expression is critical for guiding GBM treatment, particularly in patients with therapy-resistant MES subtypes. In this study, we identify the ubiquitin-specific peptidase 21 (USP21) as a critical FOXD1 deubiquitinase in MES GSCs. We find that USP21 directly interacts with and stabilizes FOXD1 by reverting its proteolytic ubiquitination. Silencing of USP21 enhances polyubiquitination of FOXD1, promotes its proteasomal degradation, and ultimately attenuates MES identity in GSCs, while these effects could be largely restored by reintroduction of FOXD1. Remarkably, we show that disulfiram, a repurposed drug that could block the enzymatic activities of USP21, suppresses GSC tumorigenicity in MES GSC-derived GBM xenograft model. Additionally, we demonstrate that USP21 is overexpressed and positively correlated with FOXD1 protein levels in GBM tissues, and its expression is inversely correlated with patient survival. Collectively, our work reveals that USP21 maintains MES identity by antagonizing FOXD1 ubiquitination and degradation, suggesting that USP21 is a potential therapeutic target for the MES subtype of GBM.

Study of the Fluidized Separation Process of Irregular Coarse-Grained Pulverized Coal Agglomerates Based on Modified Computational Fluid Dynamics-Population Balance Method.

In this work, the agglomeration, fragmentation, and separation process of coarse-grained pulverized coal agglomerates (CGPCA) obtained from a power plant were achieved using gas-solid fluidized bed sorting and analyzed through a combination of numerical simulations and actual experiments with CGPCA. To study the polydispersity and irregularity of CGPCA, the CGPCA surface fractal dimension was calculated using fractal dimension combined with scanning electron microscopy. The two-section fractal dimension of the particle size distribution was obtained by fitting the logarithmic particle size distribution of CGPCA. On the basis of the obtained data, the polydisperse particle drag force model, the agglomeration kernel function, and the breakage kernel function were modified. Thus, an irregular polydisperse gas-solid two-phase Eulerian-Eulerian model was constructed to simulate the sorting process of CGPCA in the fluidized bed. The results of the numerical simulation investigation were compared with the experimental results and showed that the simulation data, which considered the two section fractal dimension, was in better agreement with the experimental results. The cumulative logarithmic distribution of CGPCA's size was segmented and fitted. The values of the two section fractals of the agglomerates were determined as D = 1.014 and D = 2.401, respectively. Analysis revealed that the optimal separation efficiency working condition in the simulation process, providing the highest separation efficiency of 54.7%, was generated at air velocity of 1.21 m/s.

Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker.

Background: Glioma, the most frequent malignant tumor of the neurological system, has a poor prognosis and treatment problems. Glioma's tumor microenvironment is also little known. Methods: We downloaded glioma data from the TCGA database. The patients in the TCGA database were split into two groups, one for training and the other for validation. The ubiquitination genes were then evaluated in glioma using COX and Lasso regression to create a ubiquitination-related signature. We assessed the signature's predictive usefulness and role in the immune microenvironment after it was generated. Finally, in vitro experiment were utilized to check the expression and function of the signature's key gene, USP4. Results: This signature can be used to categorize glioma patients. Glioma patients can be separated into high-risk and low-risk groups in both the training and validation cohorts, with the high-risk group having a significantly worse prognosis (P<0.05). Following further investigation of the immune microenvironment, it was discovered that this risk grouping could serve as a guide for glioma immunotherapy. The activity, invasion and migration capacity, and colony formation ability of U87-MG and LN229 cell lines were drastically reduced after the important gene USP4 in signature was knocked down in cell tests. Overexpression of USP4 in the A172 cell line, on the other hand, greatly improved clonogenesis, activity, invasion and migration. Conclusions: Our research established a foundation for understanding the role of ubiquitination genes in gliomas and identified USP4 as a possible glioma biomarker.