Moiré-of-Moiré phases formed in twisted graphene/hexagonal boron nitride heterostructures under high pressure.

The atomistic behavior and mechanical properties of twisted graphene/h-BN (T-GBN) heterostructures under hydrostatic high-pressure is investigated using density functional theory with the Perdew-Burke-Ernzerhof functional. Systematic explorations of T-GBN heterostructures with different twist angles (9.43°, 13.17°, and 21.78° characterized by moiré patterns) reveal that stable phases, denoted as Moiré-BC2N (m-BC2N), are formed. Notably, the m-BC2N (21.78°) phase maintains perfect sp3 hybridization, even upon complete relaxation to zero pressure, and its mechanical stability is confirmed; comprehensive mechanical evaluations unveil the crystal anisotropic attributes, further highlighting its exceptionally high hardness. Specifically, m-BC2N (21.78°) demonstrates an impressive hardness of 74.7 GPa. Furthermore, electronic structure analysis of m-BC2N exhibits wide bandgaps (Eg), , comparable to diamond, while m-BC2N (9.43°) exhibits a lower bandgap, . This study sheds light on designing novel BCN ternary structures with outstanding mechanical properties under high pressures.

Graphene nanoribbon woven fabric against the impact of a cylindrical projectile.

Graphene nanoribbon woven fabrics (GNWFs) with excellent mechanical properties are promising for ballistic armor materials. The dynamic response of single-layer and bilayer GNWFs under nano-projectile impact at high-speed (4-5 km s-1) is investigated by molecular dynamics simulations. Results show that the woven structure is determined by the bandwidth and gap spacing, which influences the deformation/fracture and motion coupling effects of the crossed nanoribbons and the ballistic performance of GNWF. Owing to the perturbation of the van der Waals (vdW) interface between nanoribbons, the specific penetration energy of GNWFs reaches 16.02 MJ kg-1, which is much higher than that of single-layer graphene (10.80 MJ kg-1) and bilayer graphene (10.07 MJ kg-1). The peculiarities of woven structure minimize the damage of GNWFs, on the one hand, the reversibility of vdW interactions and the entanglement of nanoribbons provide GNWFs a certain self-healing ability. On the other hand, the porous nanostructure of twist-stacked bilayer GNWFs tends to be uniform and dense with the twist angle, which improves the impact resistance. This study provides more understanding of the ballistic properties of GNWFs and the design of nano-fabrics based on two-dimensional materials.

Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.

Translocation of 14-3-3 protein epsilon (14-3-3ε) was found to be involved in Triptolide (Tp)-induced inhibition of colorectal cancer (CRC) cell proliferation. However, the form of cell death induced by 14-3-3ε translocation and mechanisms underlying this effect remain unclear. This study employed label-free LC-MS/MS to identify 14-3-3ε-associated proteins in CRC cells treated with or without Tp. Our results confirmed that heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C) were exported out of the nucleus by 14-3-3ε and degraded by ubiquitination. The nucleo-cytoplasmic shuttling of 14-3-3ε carrying hnRNP C mediated Tp-induced proliferation inhibition, cell cycle arrest and autophagic processes. These findings have broad implications for our understanding of 14-3-3ε function, provide an explanation for the mechanism of nucleo-cytoplasmic shuttling of hnRNP C and provide new insights into the complex regulation of autophagy.

Comparison between unilateral curved and bilateral straight percutaneous vertebral augmentation in the treatment of osteoporotic vertebral compression fractures: A meta-analysis.

OBJECTIVES: The aim of this meta-analysis was to compare the efficacy and safety of unilateral curved and bilateral straight percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fractures (OVCFs). MATERIALS AND METHODS: We performed a comprehensive literature search from electronic databases including Springer, Web of Science, PubMed, Cochrane Library databases and ScienceDirect up to July 2022. Three randomized-controlled trials (RCTs) and one retrospective study which met the inclusion criteria were analyzed. RESULTS: There were significant differences in the operative time, injected bone cement volume, bone cement leakage rate and X-ray frequency between the bilateral straight PVA and unilateral curved PVA. No significant differences were found regarding postoperative Cobb angle, Visual Analog Scale or Oswestry Disability Index between the two groups. CONCLUSION: Compared to bilateral straight PVA, unilateral curved PVA may decrease operative time, injected bone cement volume, bone cement leakage rate, and X-ray frequency in the treatment of OVCFs. However, the Cobb angle, pain, and clinical scores are comparable. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required.

Comparison between peri-articular injection and intra-articular injection of tranexamic acid during total knee arthroplasty: A meta-analysis.

OBJECTIVES: In this meta-analysis, we aimed to compare the efficacy and safety of peri-articular injection (PAI) and intraarticular injection (IAI) of tranexamic acid (TXA) in total knee arthroplasty (TKA). PATIENTS AND METHODS: We performed a comprehensive literature search from electronic databases such as Springer, Web of Science, PubMed, Cochrane Library databases, and ScienceDirect up to October 2021. The language of identified articles was not restricted. The keywords used for the search strategy included: "tranexamic acid", "total knee arthroplasty", "peri-articular injection" and "intra-articular injection". RESULTS: Two randomized-controlled trials (RCTs) and four non-RCTs with a total of 491 patients met the inclusion criteria. Of the patients, 242 patients were in the PAI group and 249 patients were in the IAI group. No significant difference was observed between the two groups in hemoglobin drop, postoperative drainage volume, total blood loss, blood transfusion requirements, or units of blood transfused. There was no significant difference between the two groups regarding postoperative infection or deep venous thrombosis. CONCLUSION: The PAI of TXA is comparable to IAI of TXA in decreasing postoperative blood loss during TKA.

LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway.

Background: LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined. Methods: In this study, expression level data and clinical information were obtained via three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. In vitro and in vivo assays were used to explore the function of LMO1 in human glioma. Gene set enrichment analysis (GSEA), RNA-seq and western blot were used to explore the potential molecular mechanisms. A prognostic model was built for predicting the overall survival(OS) of human glioma patients. Results: High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. High levels of LMO1 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) and 1p/19q non-codeletion gliomas. Gene silencing of LMO1 significantly inhibited tumor growth, invasion and migration in vitro. In contrast, LMO1 over-expression promoted tumor growth, invasion and migration. Mechanically, LMO1 may positively regulate the level of NGFR mRNA and protein. NGFR mediated the regulation between LMO1 and NF-kB activation. Consistently, the nude mice study further confirmed that knockdown of LMO1 blocked tumor growth via NGFR-NF-kB axis. Finally, The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk. Conclusion: This study provides new insights and evidences that high level expression of LMO1 is significantly correlated with progression and prognosis in human gliomas. LMO1 played a critical role in tumorigenesis and progression. The present study first investigated the LMO1-NGFR-NF-kB axis regulate cell growth and invasion in human glioma cells, whereby targeting this pathway may be a therapeutic target for glioma.

Comparison between Zip-Type Skin Closure Device and Staple for Total Knee Arthroplasty: A Meta-Analysis.

PURPOSE: To compare the efficacy and safety of zip-type skin closure device (SCD) and staple in total knee arthroplasty (TKA). METHODS: Potential academic articles were identified from PubMed, Springer, ScienceDirect, and Cochrane Library from the inception of electronic databases to July 2020. The statistical analyses were performed with RevMan 5.1. RESULTS: One randomized controlled trial (RCT) and 5 non-RCTs met the inclusion criteria. Present meta-analysis reveals that SCD is associated with lower wound pain score, scar score, and readmission compared with a staple. No significant differences are identified in terms of wound total complications, dehiscence, blisters, and infection. CONCLUSIONS: Comparing with a staple, zip-type SCD is a less painful skin closure method with fewer medical cost undergoing TKA.

Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype.

BACKGROUND: The glioblastoma (GBM) mesenchymal (MES) phenotype, induced by NF-κB activation, is characterized by aggressive tumor progression and poor clinical outcomes. Our previous analysis indicated that MES GBM has a unique alternative splicing (AS) pattern; however, the underlying mechanism remains obscure. We aimed to reveal how splicing regulation contributes to MES phenotype promotion in GBM. METHODS: We screened novel candidate splicing factors that participate in NF-κB activation and MES phenotype promotion in GBM. In vitro and in vivo assays were used to explore the function of RSRP1 in MES GBM. RESULTS: Here, we identified that arginine/serine-rich protein 1 (RSRP1) promotes the MES phenotype by facilitating GBM cell invasion and apoptosis resistance. Proteomic, transcriptomic, and functional analyses confirmed that RSRP1 regulates AS in MES GBM through mediating spliceosome assembly. One RSRP1-regulated AS event resulted in skipping PARP6 exon 18 to form truncated, oncogenic PARP6-s. This isoform was unable to effectively suppress NF-κB. Cotreatment of cultured GBM cells and GBM tumor-bearing mice with spliceosome and NF-κB inhibitors exerted a synergistic effect on MES GBM growth. CONCLUSION: We identified a novel mechanism through which RSRP1-dependent splicing promotes the GBM MES phenotype. Targeting AS via RSRP1-related spliceosomal factors might constitute a promising treatment for GBM.

Preparation of carbon nanofibrous mats encapsulating zero-valent Fe nanoparticles as Fe reservoir for removal of organic pollutants.

Zero-valent iron nanoparticles (ZVI NPs) display promising potential in the removal of organic pollutants and heavy metal ions for environmental remediation. However, it is crucial to prevent the oxidation of ZVI NP and control the release of Fe ions under storage and working conditions. In this study, ZVI NPs are encapsulated in single-axial and co-axial carbon nanofibers by electrospinning polyacrylonitrile (PAN)/Fe3+ nanofibrous mats with different structures and then annealing the PAN nanofibrous mats in reduction atmosphere. SEM images show that the diameter of the carbon nanofibers is affected by the structure of the nanofibers and the ZVI NPs content after the annealing treatment. The formation of ZVI NPs is confirmed through XPS spectra and HRTEM characterization. The catalytic degradation of organic pollutants by ZVI NPs encapsulated in the carbon nanofibrous mats is evaluated using methylene blue (MB). The results show that the degradation rate of MB is significantly improved when the ZVI NP content encapsulated in the nanofibers increased. MB is completely degraded by the nanofibrous mats with either the single-axial structure or the co-axial structure, but at a higher degradation rate by the single-axial structure than that by the co-axial structure. These results provide alternatives to utilize the carbon nanofibrous mats encapsulating ZVI NPs as Fe reservoir for the removal of organic pollutants in an emergent or long-term situation for environmental remediation.

Preparation of Poly(ether-ether-ketone)/Nanohydroxyapatite Composites with Improved Mechanical Performance and Biointerfacial Affinity.

Poly(ether-ether-ketone) (PEEK) displays promising potential in hard tissue repair and orthopedic surgery due to its adaptable mechanical performance, good chemical resistance, and bioinertness. However, the low biointerfacial affinity of pure PEEK implants and the decrease of mechanical strength after processing greatly limit their clinical applications. In this work, the influences on mechanical performance and biointerfacial affinity of the PEEK/nanohydroxyapatite (nHA) composites are systematically investigated. Results show that the mechanical performance of PEEK/nHA composites was improved by adjusting the nHA content. The maximum values of the tensile, compressive, bending, and impact strength of the composites were increased by approximately 16.2, 25, 54, and 21%, respectively, when compared with that of pure PEEK. Studies in vitro show that PEEK/nHA composites display good cytocompatibility and promote the biomimic formation of HA, adhesion, and proliferation of L929 cells on the surface. Studies in vivo demonstrate that, compared to the pure PEEK, PEEK/nHA composites exhibit higher biointerfacial affinity, including the adhesion and encapsulation of muscle tissues on the surface of the implants and the suppression of inflammatory reaction around the implants. Our findings could pave the way for extensive applications of PEEK/nHA composites in hard tissue repair, particularly orthopedic surgery.

Mechanically robust enzymatically degradable shape memory polyurethane urea with a rapid recovery response induced by NIR.

Biodegradable shape memory polymers have great potential for use in minimally invasive surgical procedures. Herein, a series of shape memory polyurethanes (SMPUs) containing a chymotrypsin-inspired chain extender with adjustable mechanical properties and excellent shape memory effect (SME) was prepared successfully. The chemical structure, mechanical properties, SME and in vitro degradation of the PUs were systematically characterized by proton nuclear magnetic resonance spectroscopy, tensile testing, dynamic mechanical analysis under controlled force mode, and scanning electronic microscopy. By increasing the molecular weight of poly(ε-caprolactone) (PCL) and hard segment content, a PCL4000-based SMPU with a modulus value of 115 MPa was obtained, which is three times that of a PCL2000-based sample. Further, the modulus of the PCL4000-based SMPU was increased by 50% while that of the PCL2000-based SMPU was significantly reduced when temperature increased from 23 °C to 37 °C. In addition, the PCL4000-based SMPU exhibited excellent SME with the shape fixity ratio and recovery ratio almost reaching 100%. Gold nanorods were further incorporated into the PU matrix, endowing the materials with a fast near-infrared (NIR) response in 23 s for shape recovery (NIR wavelength of 808 nm, 1.5 W). Combined with enzymatic degradability, these PU/gold-nanorod composites exhibit great potential to be used in biodegradable shape memory expanding stents.

Enhanced Hydrolytic Resistance of Fluorinated Silicon-Containing Polyether Urethanes.

The hydrolysis of a newly synthesized polyether urethane (PEU) that uses polydimethylsiloxane (PDMS) as a second macrodiol and fluorinated diol (FDO) as another chain extender has been studied via immersion in buffer solutions at 70 °C. The hydrolysis process was monitored using scanning electron microscopy (SEM), gel permeation chromatography (GPC), and tensile testing. After aging for 32 weeks, no surface defect was observed on the fluorinated silicon-containing PEUs (FSPEU). Meanwhile, the addition of FDO did not alter the other issues of bulk hydrolysis, such as the changes in molecular weight and mechanical strength. Moreover, microphase separation of FSPEU was suppressed during temperature-accelerated hydrolysis, whereas aging induced a more noticeable phase of morphological change in silicon-modified PEUs (SPEU) due to the hindrance effect of the fluorinated side chains. The formation of hydrolysis-prone allophanate is also reduced in the presence of FDO. FSPEU with enhanced antihydrolysis performance can potentially be applied to biostable medical devices.

The Effect of Negative Pressure Therapy on Closed Wound After the Orthopedic Surgery of Lower Limb: A Meta-Analysis.

Background. Negative-pressure wound therapy is applied increasingly to manage closed wounds. However, no consensus has been reached with regard to surgical site infection and wound complication. Aim. To evaluate the effect of negative pressure therapy on closed wounds after orthopedic surgeries. Methods. PubMed, EMBASE, Cochrane Library, and MEDLINE databases were searched from 1966 to January 2019; the references in the identified studies were also searched. Results. Ten studies on arthroplasty and 3 studies on fractures were included. Significantly few infections appeared in the negative pressure group (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.18-0.46, P < .001; I2 = 0%, P = .80). There was no significant difference for other complications (OR = 0.54, 95% CI = 0.21-1.39, P = .20; I2 = 81%, P < .001). Few patients needed reoperation in the negative pressure group (OR = 0.28, 95% CI = 0.14-0.53, P < .001; I2 = 0%, P = .82). Conclusion. Negative pressure therapy can decrease surgical site infection and reoperation of closed incisions.

The combination of two-dimensional and three-dimensional analysis methods contributes to the understanding of glioblastoma spatial heterogeneity.

Heterogeneity is regarded as the major factor leading to the poor outcomes of glioblastoma (GBM) patients. However, conventional two-dimensional (2D) analysis methods, such as immunohistochemistry and immunofluorescence, have limited capacity to reveal GBM spatial heterogeneity. Thus, we sought to develop an effective analysis strategy to increase the understanding of GBM spatial heterogeneity. Here, 2D and three-dimensional (3D) analysis methods were compared for the examination of cell morphology, cell distribution and large intact structures, and both types of methods were employed to dissect GBM spatial heterogeneity. The results showed that 2D assays showed only cross-sections of specimens but provided a full view. To visualize intact GBM specimens in 3D without sectioning, the optical tissue clearing methods CUBIC and iDISCO+ were used to clear opaque specimens so that they would become more transparent, after which the specimens were imaged with a two-photon microscope. The 3D analysis methods showed specimens at a large spatial scale at cell-level resolution and had overwhelming advantages in comparison to the 2D methods. Furthermore, in 3D, heterogeneity in terms of cell stemness, the microvasculature, and immune cell infiltration within GBM was comprehensively observed and analysed. Overall, we propose that 2D and 3D analysis methods should be combined to provide much greater detail to increase the understanding of GBM spatial heterogeneity.

Quantitative Proteomics Analysis Reveals Nuclear Perturbation in Human Glioma U87 Cells treated with Temozolomide.

Glioblastoma (GBM) is the most malignant and aggressive glioma, which has a very poor prognosis. Temozolomide (TMZ) is still a first-line treatment, but resistance is inevitable even in MGMT-deficient glioblastoma cells. The aims of this study were to comprehend the effect of TMZ on nucleus and the underlying mechanism of acquired TMZ resistance in MGMT-deficient GBM. We show the changes of nuclear proteome in the MGMT-deficient GBM U87 cells treated with TMZ for 1 week. Label-free-based quantitative proteomics were used to investigate nuclear protein abundance change. Subsequently, gene ontology function annotation, KEGG pathway analysis, protein-protein interaction (PPI) network construction analysis of DAPs, and immunofluorescence were applied to validate the quality of proteomics. In total, 457 (455 gene products) significant DAPs were identified, of which 327 were up-regulated and 128 were down-regulated. Bioinformatics analysis uncovered RAD50, MRE11, UBR5, MSH2, MSH6, DDB1, DDB2, RPA1, RBX1, CUL4A, and CUL4B mainly enriched in DNA damage repair related pathway and constituted a protein-protein interaction network. Ribosomal proteins were down-regulated. Cells were in a stress-responsive state, while the entire metabolic level was lowered. SIGNIFICANCE OF THE STUDY: In U87 cell treated with TMZ for 1 week, which resulted in DNA damage, we found various proteins dysregulated in the nucleus. Some proteins related to the DNA damage repair pathway were up-regulated, and there was a strong interaction. We believe this is the potential clues of chemotherapy resistance in tumour cells. These proteins can be used as indicators of tumour resistance screening in the future.

Classification of glioma based on prognostic alternative splicing.

BACKGROUND: Previously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS. METHODS: Using the TCGA glioblastoma (GBM) and low-grade glioma (LGG) datasets, we analyzed prognostic splicing events. Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events. RESULTS: We analyzed prognostic splicing events and proposed novel splicing classifications across pan-glioma samples (labeled pST1-7) and across GBM samples (labeled ST1-3). Distinct splicing profiles between GBM and LGG were observed, and the primary discriminator for the pan-glioma splicing classification was tumor grade. Subtype-specific splicing events were identified; one example is AS of zinc finger proteins, which is involved in glioma prognosis. Furthermore, correlation analysis of splicing factors and splicing events identified SNRPB and CELF2 as hub splicing factors that upregulated and downregulated oncogenic AS, respectively. CONCLUSION: A comprehensive analysis of AS in glioma was conducted in this study, shedding new light on glioma heterogeneity and providing new insights into glioma diagnosis and treatment.

Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2.

The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O6-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

Free-standing supercapacitors from Kraft lignin nanofibers with remarkable volumetric energy density.

We have discovered a very simple method to address the challenge associated with the low volumetric energy density of free-standing carbon nanofiber electrodes for supercapacitors by electrospinning Kraft lignin in the presence of an oxidizing salt (NaNO3) and subsequent carbonization in a reducing atmosphere. The presence of the oxidative salt decreases the diameter of the resulting carbon nanofibers doubling their packing density from 0.51 to 1.03 mg cm-2 and hence doubling the volumetric energy density. At the same time, the oxidative NaNO3 salt eletrospun and carbonized together with lignin dissolved in NaOH acts as a template to increase the microporosity, thus contributing to a good gravimetric energy density. By simply adjusting the process parameters (amount of oxidizing/reducing agent), the gravimetric and volumetric energy density of the resulting lignin free-standing carbon nanofiber electrodes can be carefully tailored to fit specific power to energy demands. The areal capacitance increased from 147 mF cm-2 in the absence of NaNO3 to 350 mF cm-2 with NaNO3 translating into a volumetric energy density increase from 949 µW h cm-3 without NaNO3 to 2245 µW h cm-3 with NaNO3. Meanwhile, the gravimetric capacitance also increased from 151 F g-1 without to 192 F g-1 with NaNO3.

miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma.

INTRODUCTION: Temozolomide (TMZ) is the preferred chemotherapeutic drug approved for the Glioblastoma multiforme (GBM) treatment. However, resistance to TMZ is the most intractable challenge for treatment of GBM. Screening of miRNAs is becoming a novel strategy to reveal underlying mechanism of drug-resistance of human tumors. MATERIALS AND METHODS: We conducted RNA sequencing (RNA-seq) for GBM cells treated continuously with TMZ 1 or 2 week or not. Bioinformatic analysis was used to predict targets of these altered miRNAs. Subsequently, we studied the potential role of miR-1268a in TMZ-resistance of GBM cells. RESULTS: Expression levels of 55 miRNAs were identified altering both after 1 and 2 weeks TMZ treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to illuminate the biological implication and related pathways of predicted target genes. We showed that miR-1268a was downregulated after TMZ treatment and targeted ABCC1/MRP1, a membrane transporter contributing to drug resistance, using dual-luciferase assay. Furthermore, we confirmed overexpression of miR-1268a inhibited protein translation of ABCC1 and restored upregulated expression of ABCC1 due to TMZ. Inversely, knockdown of miR-1268a increased ABCC1 at protein level and enhanced upregulation of ABCC1 with TMZ treatment. In addition, our data indicated that miR-1268a enhanced TMZ sensitivity in GBM cells. CONCLUSION: Through RNA-seq analysis, we discovered miR-1268a and elucidated its role in modulating TMZ-resistance of GBM cells by targeting ABCC1.

Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based on Subcellular Proteomics and Bioinformatical Analysis.

TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.