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1.
Small ; : e2312124, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751072

RESUMO

Rechargeable metal batteries have received widespread attention due to their high energy density by using pure metal as the anode. However, there are still many fundamental problems that need to be solved before approaching practical applications. The critical ones are low charge/discharge current due to slow ion transport, short cycle lifetime due to poor anode/cathode stability, and unsatisfied battery safety. To tackle these problems, various strategies have been suggested. Among them, electrolyte additive is one of the most widely used strategies. Most of the additives currently studied are soluble, but their reliability is questionable, and they can easily affect the electrochemical process, causing unwanted battery performance decline. On the contrary, insoluble additives with excellent chemical stability, high mechanical strength, and dimensional tunability have attracted considerable research exploration recently. However, there is no timely review on insoluble additives in metal batteries yet. This review summarizes various functions of insoluble additives: ion transport modulation, metal anode protection, cathode amelioration, as well as battery safety enhancement. Future research directions and challenges for insoluble solid additives are also proposed. It is expected this review will stimulate inspiration and arouse extensive studies on further improvement in the overall performance of metal batteries.

2.
Biofactors ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696072

RESUMO

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.

3.
Cancer Lett ; 593: 216875, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643837

RESUMO

Mesenchymal glioma stem cells (MES GSCs) are a subpopulation of cells in glioblastoma (GBM) that contribute to a worse prognosis owing to their highly aggressive nature and resistance to radiation therapy. Here, OCT4 is characterized as a critical factor in sustaining the stemness phenotype of MES GSC. We find that OCT4 is expressed intensively in MES GSC and is intimately associated with poor prognosis, moreover, OCT4 depletion leads to diminished invasive capacity and impairment of the stem phenotype in MES GSC. Subsequently, we demonstrated that USP5 is a deubiquitinating enzyme which directly interacts with OCT4 and preserves OCT4 stability through its deubiquitination. USP5 was additionally proven to be aberrantly over-expressed in MES GSCs, and its depletion resulted in a noticeable diminution of OCT4 and consequently a reduced self-renewal and tumorigenic capacity of MES GSCs, which can be substantially restored by ectopic expression of OCT4. In addition, we detected the dominant molecule that regulates USP5 transcription, E2F1, with dual luciferase reporter gene analysis. In combination, targeting the E2F1-USP5-OCT4 axis is a potentially emerging strategy for the therapy of GBM.

5.
Clin Transl Oncol ; 26(6): 1467-1479, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38190034

RESUMO

PURPOSE: Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment. METHODS: This retrospective study collected data from 1994 breast cancer patients who underwent NAT. Relevant clinical and pathological characteristics were included, and pre- and post-treatment complete blood cell counts were evaluated to calculate four systemic immune-inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). The optimal cutoff values for these markers were determined using ROC curves, and patients were classified into high-value and low-value groups based on these cutoff values. Univariate and multivariate logistic regression analyses were conducted to analyze factors influencing pCR. The factors with independent predictive value were used to construct a nomogram. RESULTS: After NAT, 383 (19.2%) patients achieved pCR. The area under the ROC curve is generally larger for post-treatment markers compared to pre-treatment markers. Pre-treatment NLR and PLR, as well as post-treatment LMR and SII, were identified as independent predictive factors for pCR, along with Ki-67, clinical tumor stage, clinical lymph node stage, molecular subtype, and clinical response. Higher pre-NLR (OR = 1.320; 95% CI 1.016-1.716; P = 0.038), pre-PLR (OR = 1.474; 95% CI 1.058-2.052; P = 0.022), post-LMR (OR = 1.532; 95% CI 1.175-1.996; P = 0.002), and lower post-SII (OR = 0.596; 95% CI 0.429-0.827; P = 0.002) are associated with a higher likelihood of achieving pCR. The established nomogram had a good predictive performance with an area under the ROC curve of 0.754 (95% CI 0.674-0.835). CONCLUSION: Both pre- and post-treatment systemic immune-inflammatory markers have a significant predictive role in achieving pCR after NAT in breast cancer patients. Indeed, it is possible that post-treatment markers have stronger predictive ability compared to pre-treatment markers.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Neutrófilos , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Curva ROC , Biomarcadores Tumorais/sangue , Linfócitos , Idoso , Inflamação/sangue , Valor Preditivo dos Testes , Nomogramas , Plaquetas/patologia , Monócitos , Prognóstico
6.
Angew Chem Int Ed Engl ; 63(4): e202316904, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38059793

RESUMO

Aqueous zinc ion batteries are gaining popularity due to their high energy density and environmental friendliness. However, random deposition of zinc ions on the anode and sluggish migration of zinc ions on the interface would lead to the growth of zinc dendrites and poor cycling performance. To address these challenges, we developed a fluorinated solid-state-electrolyte interface layer composed of Ca5 (PO4 )3 F/Zn3 (PO4 )2 via an in situ ion exchange strategy to guide zinc-ion oriented deposition and fast zinc ion migration on the anode during cycling. The introduction of Ca5 (PO4 )3 F (FAP) can increase the nucleation sites of zinc ions and guide the oriented deposition of zinc ions along the (002) crystal plane, while the in situ formation of Zn3 (PO4 )2 during cycling can accelerate the migration of zinc ions. Benefited from our design, the assembled Zn//V2 O5 ⋅ H2 O batteries based on FAP-protected Zn anode (FAP-Zn) achieve a higher capacity retention of 84 % (220 mAh g-1 ) than that of bare-Zn based batteries, which have a capacity retention of 23 % (97 mAh g-1 ) at 3.0 A g-1 after 800 cycles. This work provides a new solution for the rational design and development of the solid-state electrolyte interface layer to achieve high-performance zinc-ion batteries.

7.
Small ; 20(6): e2306262, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37775338

RESUMO

Low Coulombic efficiency, low-capacity retention, and short cycle life are the primary challenges faced by various metal-ion batteries due to the loss of corresponding active metal. Practically, these issues can be significantly ameliorated by compensating for the loss of active metals using pre-metallization techniques. Herein, the state-of-the-art development in various pr-emetallization techniques is summarized. First, the origin of pre-metallization is elaborated and the Coulombic efficiency of different battery materials is compared. Second, different pre-metallization strategies, including direct physical contact, chemical strategies, electrochemical method, overmetallized approach, and the use of electrode additives are summarized. Third, the impact of pre-metallization on batteries, along with its role in improving Coulombic efficiency is discussed. Fourth, the various characterization techniques required for mechanistic studies in this field are outlined, from laboratory-level experiments to large scientific device. Finally, the current challenges and future opportunities of pre-metallization technology in improving Coulombic efficiency and cycle stability for various metal-ion batteries are discussed. In particular, the positive influence of pre-metallization reagents is emphasized in the anode-free battery systems. It is envisioned that this review will inspire the development of high-performance energy storage systems via the effective pre-metallization technologies.

8.
Small ; 20(16): e2307027, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38018336

RESUMO

Fast charging lithium (Li)-ion batteries are intensively pursued for next-generation energy storage devices, whose electrochemical performance is largely determined by their constituent electrode materials. While nanosizing of electrode materials enhances high-rate capability in academic research, it presents practical limitations like volumetric packing density and high synthetic cost. As an alternative to nanosizing, microscale electrode materials cannot only effectively overcome the limitations of the nanosizing strategy but also satisfy the requirement of fast-charging batteries. Therefore, this review summarizes the new emerging microscale electrode materials for fast charging from the commercialization perspective. First, the fundamental theory of electronic/ionic motion in both individual active particles and the whole electrode is proposed. Then, based on these theories, the corresponding optimization strategies are summarized toward fast-charging microscale electrode materials. In addition, advanced functional design to tackle the mechanical degradation problems related to next generation high capacity alloy- and conversion-type electrode materials (Li, S, Si et al.) for achieving fast charging and stable cycling batteries. Finally, general conclusions and the future perspective on the potential research directions of microscale electrode materials are proposed. It is anticipated that this review will provide the basic guidelines for both fundamental research and practical applications of fast-charging batteries.

9.
Small ; 20(11): e2306939, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37929662

RESUMO

The performance of zinc-ion batteries is severely hindered by the uncontrolled growth of dendrites and the severe side reactions on the zinc anode interface. To address these challenges, a weak-water-coordination electrolyte is realized in a peptone-ZnSO4 -based electrolyte to simultaneously regulate the solvation structure and the interfacial environment. The peptone molecules have stronger interaction with Zn2+ ions than with water molecules, making them more prone to coordinate with Zn2+ ions and then reducing the active water in the solvated sheath. Meantime, the peptone molecules selectively adsorb on the Zn metal surface, and then are reduced to form a stable solid-electrolyte interface layer that can facilitate uniform and dense Zn deposition to inhabit the dendritic growth. Consequently, the Zn||Zn symmetric cell can exhibit exceptional cycling performance over 3200 h at 1.0 mA cm-2 /1.0 mAh cm-2 in the peptone-ZnSO4 -based electrolyte. Moreover, when coupled with a Na2 V6 O16 ·3H2 O cathode, the cell exhibits a long lifespan of 3000 cycles and maintains a high capacity retention rate of 84.3% at 5.0 A g-1 . This study presents an effective approach for enabling simultaneous regulation of the solvation structure and interfacial environment to design a highly reversible Zn anode.

10.
Opt Express ; 31(20): 32813-32823, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859075

RESUMO

Optical frequency combs with more than 10 W have paved the way for extreme ultraviolet combs generation by interaction with inert gases, leading to extreme nonlinear spectroscopy and the ultraviolet nuclear clock. Recently, the demand for an ultra-long-distance time and frequency space transfer via optical dual-comb proposes a new challenge for high power frequency comb in respect of power scaling and optical frequency stability. Here we present a frequency comb based on fiber chirped pulse amplification (CPA), which can offer more than 20 W output power. We further characterize the amplifier branch noise contribution by comparing two methods of locking to an optical reference and measure the out-of-loop frequency instability by heterodyning two identical high-power combs. Thanks to the low noise CPA, reasonable locking method, and optical path-controlled amplifiers, the out-of-loop beat note between two combs demonstrates the unprecedented frequency stability of 4.35 × 10-17 at 1s and 6.54 × 10-19 at 1000 s.

11.
Nano Lett ; 23(17): 8326-8330, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37611221

RESUMO

Bacterially induced sepsis requires rapid bacterial detection and identification. Hours count for critically ill septic patients, while current culture-based detection requires at least 10 h up to several days. Here, we apply a microfluidic device equipped with a bacterially activated, macrophage-membrane-coating on nanowired-Si adsorbent surfaces for rapid, bacterial detection and Gram-identification in bacterially contaminated blood. Perfusion of suspensions of Gram-negative or Gram-positive bacteria through a microfluidic device equipped with membrane-coated adsorbent surfaces detected low (<10 CFU/mL) bacterial levels. Subsequent, in situ fluorescence-staining yielded Gram-identification for guiding antibiotic selection. In mixed Escherichia coli and Staphylococcus aureus suspensions, Gram-negative and Gram-positive bacteria were detected in the same ratios as those fixed in suspension. Results were validated with a 100% correct score by blinded evaluation (two observers) of 15 human blood samples, spiked with widely different bacterial strains or combinations of strains, demonstrating the potential of the platform for rapid (1.5 h in total) diagnosis of bacterial sepsis.


Assuntos
Bactérias , Sepse , Humanos , Suspensões , Dispositivos Lab-On-A-Chip , Escherichia coli , Macrófagos , Sepse/diagnóstico
12.
Mater Horiz ; 10(9): 3680-3693, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37365987

RESUMO

Aqueous zinc-ion batteries (ZIBs) are promising candidates for next-generation energy storage systems due to their intrinsic safety, environmental friendliness, and low cost. However, the uncontrollable Zn dendrite growth during cycling is still a critical challenge for the long-term operation of ZIBs, especially under harsh lean-Zn conditions. Herein, we report nitrogen and sulfur-codoped carbon quantum dots (N,S-CDs) as zincophilic electrolyte additives to regulate the Zn deposition behaviors. The N,S-CDs with abundant electronegative groups can attract Zn2+ ions and co-deposit with Zn2+ ions on the anode surface, inducing a parallel orientation of the (002) crystal plane. The deposition of Zn preferentially along the (002) crystal direction fundamentally avoids the formation of Zn dendrites. Moreover, the co-depositing/stripping feature of N,S-CDs under an electric field force ensures the reproducible and long-lasting modulation of the Zn anode stability. Benefiting from these two unique modulation mechanisms, stable cyclability of the thin Zn anodes (10 and 20 µm) at a high depth of discharge (DOD) of 67% and high Zn||Na2V6O16·3H2O (NVO, 11.52 mg cm-2) full-cell energy density (144.98 W h Kg-1) at a record-low negative/positive (N/P) capacity ratio of 1.05 are achieved using the N,S-CDs as an additive in ZnSO4 electrolyte. Our findings not only offer a feasible solution for developing actual high-energy density ZIBs but also provide in-depth insights into the working mechanism of CDs in regulating Zn deposition behaviors.

13.
Cancers (Basel) ; 15(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37173997

RESUMO

(1) Background: The aim of this study was to explore the predictive ability of lymphocyte subsets for the prognosis of gastric cancer patients who underwent surgery and the prognostic value of CD19 (+) B cell combined with the Prognostic Nutritional Index (PNI). (2) Methods: This study involved 291 patients with gastric cancer who underwent surgery at our institution between January 2016 and December 2017. All patients had complete clinical data and peripheral lymphocyte subsets. Differences in clinical and pathological characteristics were examined using the Chi-square test or independent sample t-tests. The difference in survival was evaluated using Kaplan-Meier survival curves and the Log-rank test. Cox's regression analysis was performed to identify independent prognostic indicators, and nomograms were used to predict survival probabilities. (3) Results: Patients were categorized into three groups based on their CD19 (+) B cell and PNI levels, with 56 cases in group one, 190 cases in group two, and 45 cases in group three. Patients in group one had a shorter progression-free survival (PFS) (HR = 0.444, p < 0.001) and overall survival (OS) (HR = 0.435, p < 0.001). CD19 (+) B cell-PNI had the highest area under the curve (AUC) compared with other indicators, and it was also identified as an independent prognostic factor. Moreover, CD3 (+) T cell, CD3 (+) CD8 (+) T cell, and CD3 (+) CD16 (+) CD56 (+) NK T cell were all negatively correlated with the prognosis, while CD19 (+) B cell was positively associated with the prognosis. The C-index and 95% confidence interval (CI) of nomograms for PFS and OS were 0.772 (0.752-0.833) and 0.773 (0.752-0.835), respectively. (4) Conclusions: Lymphocyte subsets including CD3 (+) T cell, CD3 (+) CD8 (+) T cell, CD3 (+) CD16 (+) CD56 (+) NK T cell, and CD19 (+) B cell were related to the clinical outcomes of patients with gastric cancer who underwent surgery. Additionally, PNI combined with CD19 (+) B cell had higher prognostic value and could be used to identify patients with a high risk of metastasis and recurrence after surgery.

14.
Small ; 19(23): e2207093, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36890773

RESUMO

Lithium metal batteries (LMBs) are promising for next-generation high-energy-density batteries owing to the highest specific capacity and the lowest potential of Li metal anode. However, the LMBs are normally confronted with drastic capacity fading under extremely cold conditions mainly due to the freezing issue and sluggish Li+ desolvation process in commercial ethylene carbonate (EC)-based electrolyte at ultra-low temperature (e.g., below -30 °C). To overcome the above challenges, an anti-freezing carboxylic ester of methyl propionate (MP)-based electrolyte with weak Li+ coordination and low-freezing temperature (below -60 °C) is designed, and the corresponding LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode exhibits a higher discharge capacity of 84.2 mAh g-1 and energy density of 195.0 Wh kg-1 cathode than that of the cathode (1.6 mAh g-1 and 3.9 Wh kg-1 cathode ) working in commercial EC-based electrolytes for NCM811‖ Li cell at -60 °C. Molecular dynamics simulation, Raman spectra, and nuclear magnetic resonance characterizations reveal that rich mobile Li+ and the unique solvation structure with weak Li+ coordination are achieved in MP-based electrolyte, which collectively facilitate the Li+ transference process at low temperature. This work provides fundamental insights into low-temperature electrolytes by regulating solvation structure, and offers the basic guidelines for the design of low-temperature electrolytes for LMBs.

15.
Front Plant Sci ; 14: 1069593, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755697

RESUMO

Freshwater ecosystems are threatened by eutrophication, which causes persistent and harmful algal blooms. Filter-feeding bivalve mollusks and submerged macrophytes (SMs) alleviate the eutrophication effects by inhibiting phytoplankton biomass blooms. However, very little is known about whether and how the combined manipulation of filter-feeding bivalves and SMs control eutrophication and influence phytoplankton assemblages. Here, we performed a nutrient-enriched freshwater mesocosm experiment to assess the combined effects of the filter-feeding bivalve Cristaria plicata, a cockscomb pearl mussel, and the macrophyte Hydrilla verticillate on the biomass and composition of phytoplankton assemblages. We found that addition of C. plicata and H. verticillate decreased the water nutrient concentrations and suppressed overall phytoplankton biomass. Further, distinct differences in taxa between restoration and control treatments were observed and noticeably competitive exclusion of cyanobacteria in the restoration treatments occurred. An antagonistic interaction between filter-feeding bivalves and SMs was only detected for total cyanobacteria biomass demonstrating that a larger magnitude of SM restoration may override the effect of filter-feeding bivalves. Our results suggest that manipulation, through the addition of bivalves as grazers, associated with the restoration of SMs, is an efficient approach for reducing cyanobacterial blooms and alleviating eutrophication.

16.
Food Chem ; 403: 134424, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358074

RESUMO

In this study, surimi products rich in lipids were prepared by using myofibril protein (MP) emulsion gel as carriers. The MP emulsion gel (MP concentration, c = 1.5%, oil fraction, ø = 0.68) was prepared by one-step homogenization. The emulsion gel maintained a high elastic modulus (G') after heating and freezing treatment. Confocal laser scanning microscopy revealed that the structure of the emulsion gel was a hybrid network consisting of polymers of cross-linked MP and aggregated protein-stabilized emulsion (W/O/W multiple structures) droplets. The double emulsification of the emulsion gel and MP stabilized the oil droplets in the surimi product, preventing water and oil from leaching out. The microstructure also showed smaller gaps between MPs with increased porosity, while oil droplets were stably embedded in the surimi gel matrix. Moreover, adding MP emulsion gel significantly reduced the surimi gel strength compared to adding oil directly (p < 0.05).


Assuntos
Tilápia , Animais , Emulsões/química , Géis/química , Miofibrilas/química , Proteínas/análise , Lipídeos/química
17.
Nanoscale Horiz ; 8(1): 29-54, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36268641

RESUMO

Rechargeable aqueous zinc-ion batteries (AZIBs) have attracted significant attention in large-scale energy storage systems due to their unique merits, such as intrinsic safety, low cost, and relatively high theoretical energy density. However, the dilemma of the uncontrollable Zn dendrites, severe hydrogen evolution reaction (HER), and side reactions that occur on the Zn anodes have hindered their commercialization. Herein, a state-of-the-art review of the rational design of highly reversible Zn anodes for high-performance AZIBs is provided. Firstly, the fundamental understanding of Zn deposition, with regard to the nucleation, electro-crystallization, and growth of the Zn nucleus is systematically clarified. Subsequently, a comprehensive survey of the critical factors influencing Zn plating together with the current main challenges is presented. Accordingly, the rational strategies emphasizing structural design, interface engineering, and electrolyte optimization have been summarized and analyzed in detail. Finally, future perspectives on the remaining challenges are recommended, and this review is expected to shed light on the future development of stable Zn anodes toward high-performance AZIBs.

18.
ChemSusChem ; 15(24): e202201464, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36254787

RESUMO

Lithium-ion batteries (LIBs) are momentous energy storage devices, which have been rapidly developed due to their high energy density, long lifetime, and low self-discharge rate. However, the frequent occurrence of fire accidents in laptops, electric vehicles, and mobile phones caused by thermal runaway of the inside batteries constantly reminds us of the urgency in pursuing high-safety LIBs with high performance. To this end, this Review surveyed the state-of-the-art developments of high-temperature-resistant separators for highly safe LIBs with excellent electrochemical performance. Firstly, the basic properties of separators (e. g., thickness, porosity, pore size, wettability, mechanical strength, and thermal stability) in constructing commercialized LIBs were introduced. Secondly, the working mechanisms of advanced separators with different melting points acting in the thermal runaway stage were discussed in terms of improving battery safety. Thirdly, rational design strategies for constructing high-temperature-resistant separators for LIBs with high safety were summarized and discussed, including graft modification, blend modification, and multilayer composite modification strategies. Finally, the current obstacles and future research directions in the field of high-temperature-resistant separators were highlighted. These design ideas are expected to be applied to other types of high-temperature-resistant energy storage systems working under extreme conditions.

19.
Cell Death Dis ; 13(8): 712, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974001

RESUMO

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.


Assuntos
Neoplasias Encefálicas , Fatores de Transcrição Forkhead , Glioblastoma , Células-Tronco Mesenquimais , Ubiquitina Tiolesterase , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Glioblastoma/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
20.
Front Immunol ; 13: 915709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774799

RESUMO

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.


Assuntos
Glioma , Análise de Célula Única , Proteases Específicas de Ubiquitina , Biomarcadores/análise , Perfilação da Expressão Gênica , Glioma/enzimologia , Glioma/genética , Humanos , Microambiente Tumoral/genética , Proteases Específicas de Ubiquitina/genética , Ubiquitinação
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