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1.
Nat Protoc ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890499

ABSTRACT

Covalent DNA-protein cross-links (DPCs) are pervasive DNA lesions that challenge genome stability and can be induced by metabolic or chemotherapeutic cross-linking agents including reactive aldehydes, topoisomerase poisons and DNMT1 inhibitors. The purification of x-linked proteins (PxP), where DNA-cross-linked proteins are separated from soluble proteins via electro-elution, can be used to identify DPCs. Here we describe a versatile and sensitive strategy for PxP. Mammalian cells are collected following exposure to a DPC-inducing agent, embedded in low-melt agarose plugs and lysed under denaturing conditions. Following lysis, the soluble proteins are extracted from the agarose plug by electro-elution, while genomic DNA and cross-linked proteins are retained in the plug. The cross-linked proteins can then be analyzed by standard analytical techniques such as sodium dodecyl-sulfate-polyacrylamide gel electrophoresis followed by western blotting or fluorescent staining. Alternatively, quantitative mass spectrometry-based proteomics can be used for the unbiased identification of DPCs. The isolation and analysis of DPCs by PxP overcomes the limitations of alternative methods to analyze DPCs that rely on precipitation as the separating principle and can be performed by users trained in molecular or cell biology within 2-3 d. The protocol has been optimized to study DPC induction and repair in mammalian cells but may also be adapted to other sample types including bacteria, yeast and tissue samples.

2.
EMBO J ; 43(12): 2397-2423, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38760575

ABSTRACT

The nucleoside analogue decitabine (or 5-aza-dC) is used to treat several haematological cancers. Upon its triphosphorylation and incorporation into DNA, 5-aza-dC induces covalent DNA methyltransferase 1 DNA-protein crosslinks (DNMT1-DPCs), leading to DNA hypomethylation. However, 5-aza-dC's clinical outcomes vary, and relapse is common. Using genome-scale CRISPR/Cas9 screens, we map factors determining 5-aza-dC sensitivity. Unexpectedly, we find that loss of the dCMP deaminase DCTD causes 5-aza-dC resistance, suggesting that 5-aza-dUMP generation is cytotoxic. Combining results from a subsequent genetic screen in DCTD-deficient cells with the identification of the DNMT1-DPC-proximal proteome, we uncover the ubiquitin and SUMO1 E3 ligase, TOPORS, as a new DPC repair factor. TOPORS is recruited to SUMOylated DNMT1-DPCs and promotes their degradation. Our study suggests that 5-aza-dC-induced DPCs cause cytotoxicity when DPC repair is compromised, while cytotoxicity in wild-type cells arises from perturbed nucleotide metabolism, potentially laying the foundations for future identification of predictive biomarkers for decitabine treatment.


Subject(s)
DNA (Cytosine-5-)-Methyltransferase 1 , Decitabine , Ubiquitin-Protein Ligases , Decitabine/pharmacology , Humans , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , DNA Methylation/drug effects , Antimetabolites, Antineoplastic/pharmacology , Animals , Sumoylation/drug effects
3.
Int J Surg ; 110(5): 2939-2949, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38376848

ABSTRACT

BACKGROUND: Although the COVID-19 pandemic has exerted potential impact on patients with glioblastomas (GBMs), it remains unclear whether the survival and its related risk factors of GBM patients would be altered or not during the period spanning from pre-COVID-19 to post-COVID-19 pandemic era. This study aimed to clarify the important issues above. METHODS: Two observational cohorts were utilized, including the nationwide American cohort from the Surveillance, Epidemiology, and End-Results (SEER) and the Chinese glioblastoma cohort (CGC) at our institution during 2018-2020. Demographics, tumour features, treatment regimens and clinical outcomes were collected. Cox regression model, competing risk model, and subgroup and sensitivity analysis were used to dynamically estimate the survival and its relevant risk factors over different diagnosis years from the pre-COVID-19 (2018 and 2019) to post-COVID-19 (2020) pandemic. Causal mediation analysis was further adopted to explore the potential relationship between risk factors and mortality. RESULTS: This study included 11321 GBM cases in SEER and 226 GBM patients in CGC, respectively. Instead of the diagnostic years of 2018-2020, the prognostic risk factors, such as advanced age, bilateral tumour and absence of comprehensive therapy (surgery combined with chemoradiotherapy), were identified to persistently affect GBM survival independently during the period from 2018 to 2020 in the SEER cohort (all P < 0.05). In CGC, lack of comprehensive therapy for GBM patients were restated as survival risk factors during the same timeframe. Causal mediation analysis showed that the effect of comprehensive therapy on all-cause mortality played a determinant role (direct effect value -0.227, 95% CI -0.248 to -0.207), which was partially mediated by age (9.11%) rather than tumour laterality. CONCLUSIONS: As the timeframe shifted from pre-COVID-19 to post-COVID-19 pandemic, survival of GBM patients remained stable, yet advanced age, bilateral tumours, and passive treatment continuingly impacted GBM survival. It is necessary to optimize the comprehensive treatment for GBM patients even in the post-pandemic era.


Subject(s)
Brain Neoplasms , COVID-19 , Glioblastoma , Humans , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Glioblastoma/therapy , Glioblastoma/epidemiology , Glioblastoma/mortality , Male , Female , Middle Aged , China/epidemiology , United States/epidemiology , Risk Factors , Brain Neoplasms/epidemiology , Brain Neoplasms/therapy , Brain Neoplasms/mortality , Aged , Adult , Cohort Studies , SEER Program
4.
Mitochondrion ; 75: 101836, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38158149

ABSTRACT

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor, with temozolomide (TMZ) being the standard chemotherapeutic agent for its treatment. However, TMZ resistance often develops, limiting its therapeutic efficacy and contributing to poor patient outcomes. Recent evidence highlights the crucial role of mitochondria in the development of TMZ resistance through various mechanisms, including alterations in reactive oxygen species (ROS) production, metabolic reprogramming, apoptosis regulation, biogenesis, dynamics, stress response, and mtDNA mutations. This review article aims to provide a comprehensive overview of the mitochondrial mechanisms involved in TMZ resistance and discuss potential therapeutic strategies targeting these mechanisms to overcome resistance in GBM. We explore the current state of clinical trials targeting mitochondria or related pathways in primary GBM or recurrent GBM, as well as the challenges and future perspectives in this field. Understanding the complex interplay between mitochondria and TMZ resistance will facilitate the development of more effective therapeutic strategies and ultimately improve the prognosis for GBM patients.


Subject(s)
Glioblastoma , Humans , Temozolomide/pharmacology , Glioblastoma/drug therapy , Glioblastoma/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Mitochondria/metabolism
5.
Eur Radiol ; 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37968476

ABSTRACT

OBJECTIVE: Calcification is a hallmark characteristic of oligodendroglioma (ODG) that may be used as a diagnostic factor, but its prognostic implications remain unclear. This study aimed to investigate the features of calcified ODGs and to evaluate the differences in survival between patients with calcified and noncalcified ODGs. METHODS: We retrospectively reviewed the records of 305 consecutive patients who were diagnosed with IDH-mutant, 1p/19q codeleted ODG at our institution from July 2009 to August 2020. Patients with intratumoral calcification were identified. The clinical, radiologic, and molecular features of the patients in the calcified group and noncalcified group were recorded. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Of the 305 patients, 112 (36.7%) were confirmed to have intratumoral calcification. Compared to ODGs without calcification, ODGs with calcifications had a larger tumor diameter; lower degree of resection; higher tumor grade; higher MGMT methylation level; higher Ki-67 index; and higher rates of midline crossing, enhancement, cyst, and 1q/19p copolysomy, and patients with calcification were more likely to receive chemoradiotherapy. ODGs with T2 hypointense calcification had a higher Hounsfield unit (HU) value on CT scans, and a lower degree of resection. Patients with T2 hypointense calcification ODGs had a shorter survival than those with non-hypointense calcification ODGs. ODGs with calcification and cysts showed a higher Ki-67 index, tumor grade, and enhanced rate, and the patients had an unfavorable overall survival (OS). Calcification was found to be a negative prognostic factor for both progression-free survival (PFS) and OS by univariate analysis, which was confirmed by the Cox proportional hazard model. CONCLUSIONS: Calcification is a useful negative prognostic factor for PFS and OS in patients with ODGs and could therefore be helpful in guiding personalized treatment and predicting patient prognosis. CLINICAL RELEVANCE STATEMENT: Calcification can serve as an independent prognostic factor for patients with oligodendroglioma and shows a vital role in guiding individualized treatment. KEY POINTS: • Intratumoral calcification is an independent negative prognostic risk factor for progression-free survival and overall survival in oligodendroglioma patients. • Calcifications in oligodendroglioma can be divided into hypointense and non-hypointense subtypes based on T2-weighted imaging, and patients with T2-hypointense calcification oligodendrogliomas have worse prognosis. • Calcification concurrent with cysts indicates a more aggressive phenotype of oligodendrogliomas and a significantly reduced survival rate.

6.
ACS Appl Mater Interfaces ; 15(39): 45725-45731, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37726219

ABSTRACT

Fast electron/ion transport and cycling stability of anode materials are key factors for achieving a high rate performance of battery materials. Herein, we successfully fabricated a carbon-coated Mo2C nanofiber (denoted as laser Mo2C@C) as the lithium ion battery anode material by laser carbonization of PAN-PMo12 (PAN = Polyacrylonitrile; PMo12 = H3PMo12O40). The highly graphitized carbon layer in laser Mo2C@C effectively protects Mo2C from agglomeration and flaking while facilitating electron transfer. As such, the laser Mo2C@C electrode displays an excellent electrochemical stability under 5 A g-1, with a capacity up to 300 mA h g-1 after 3000 cycles. Furthermore, the extended X-ray absorption fine structure results show the existence of some Mo vacancies in Mo2C@C. Density functional theory calculations further prove that such vacancies make the defective Mo2C@C composites energetically more favorable for lithium storage in comparison with the intact Mo2C.

7.
Lipids Health Dis ; 22(1): 114, 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37537607

ABSTRACT

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Temozolomide/pharmacology , Temozolomide/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Lipid Metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Drug Resistance, Neoplasm , Cell Line, Tumor , Xenograft Model Antitumor Assays
8.
Neurosurg Rev ; 46(1): 196, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37555964

ABSTRACT

Controversies persist regarding the benefits of surgery in elderly patients with meningiomas. The objective of this study was to develop decision-making scale to clarify the necessity for surgical intervention and provide clinical consultation for this special population. This retrospective cohort study was conducted at a single center and included 478 elderly patients (≥ 65 years) who underwent meningioma resection. Follow-up was recorded to determine recurrence and mortality rates. Univariate and multivariate analyses were performed to identify significantly preoperative factors, and prognostic prediction models were developed with determined cutoff values for the prognostic index (PI). Model discrimination was evaluated using Kaplan-Meier curves based on the PI stratification, which categorized patients into low- and high-risk groups. A decision-making tree was then established based on the risk stratification from both models. Among all patients analyzed (n = 478), 62 (13.0%) experience recurrence and 47 (10.0%) died during the follow-up period. Significantly preoperative parameters from both models included advanced age, aCCI, recurrent tumor, motor cortex involvement, male sex, peritumoral edema, and tumor located in skull base (all P < 0.05). According to the classification of PI from the two models, the decision-making tree provided four recommendations that can be used for clinical consultation. Surgery is not recommended for patients assigned to the high-risk group in both models. Patients who meet the low-risk criteria in any model may undergo surgical intervention, but the final decision should depend on the surgeon's expertise.


Subject(s)
Meningeal Neoplasms , Meningioma , Aged , Humans , Cohort Studies , Meningeal Neoplasms/surgery , Meningioma/surgery , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Treatment Outcome
9.
J Neurosurg ; 139(4): 953-964, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37561905

ABSTRACT

OBJECTIVE: Despite the controversy surrounding brain invasion (BI) as the sole indicator used to diagnose atypical meningioma, this criterion was still incorporated in the 2021 WHO classification scheme. In this study, the authors investigated the reproducibility of this prognostic effect and the impact of BI on the prognosis in otherwise benign meningioma (benign meningioma with BI). METHODS: Patients (n = 1006) with a pathological diagnosis of benign or atypical meningioma according to the latest WHO classification criteria were enrolled in this study. In patients with atypical meningioma, the cases were further categorized as benign meningioma with BI and classical atypical meningioma. Clinical, pathological, and follow-up data were collected. Kaplan-Meier curves were compared with a log-rank test, and univariate and multivariate analyses were performed. RESULTS: The study patient cohort included 282 (28.0%) individuals who were pathologically confirmed as having BI among all 1006 patients with benign or atypical meningioma. A significant difference in recurrence-free survival was observed between patients who had benign meningioma with BI and those who had classical atypical meningioma (p < 0.001), as well as between patients with benign meningiomas and those without BI (p = 0.003). Multivariate Cox analysis indicated that BI was independently associated with increased risk of relapse in the entire population (HR 1.46, 95% CI 1.01-2.12, p = 0.049) and in the atypical meningioma subcohort (HR 2.21, 95% CI 1.32-3.71, p = 0.003), as well as the benign meningioma with and without BI subcohorts (HR 1.89, 95% CI 1.01-3.56, p = 0.049). Moreover, patients with classical atypical meningiomas had a risk of relapse four times higher than those who had benign meningioma with BI (p < 0.001). CONCLUSIONS: The findings demonstrate that benign meningioma with BI typically has an intermediate prognosis and can be differentiated from benign meningioma and classical atypical meningioma, which suggests that the importance of the diagnostic effect of BI is insufficiently accounted for in grading of atypical meningioma. Increased emphasis on the presence of BI in patients with atypical meningioma may be helpful in postsurgical decision-making and facilitating improvements in individual therapy.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Meningioma/surgery , Meningeal Neoplasms/surgery , Reproducibility of Results , Neoplasm Recurrence, Local , Prognosis , Recurrence , Brain/pathology , Retrospective Studies
10.
ACS Omega ; 8(31): 28924-28931, 2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37576690

ABSTRACT

Temperature plays a crucial role in the preparation of polyvinyl chloride (PVC) gels for optical applications. Incorrect temperature selection can lead to various issues such as poor surface roughness, inadequate light transmission, and insufficient solution for optical devices. To address this challenge, this study focuses on the preparation of PVC gel samples by combining PVC powder (n = 3000), eco-friendly dibutyl adipate, and tetrahydrofuran at different stirring temperatures ranging from 40 to 70 °C. The PVC gel preparation process is categorized into four groups (T40, T50, T60, and T70) based on the mixing temperatures, employing a controlled test method with specific temperature conditions. The prepared PVC gel samples are then subjected to analysis to evaluate various properties including surface morphology, tensile strength, light transmittance, and electrical response time. Among the samples, the PVC gel prepared at 60 °C (referred to as T60) exhibits excellent optical properties, with a transmittance of 91.2% and a tensile strength of 2.07 MPa. These results indicate that 60 °C is an optimal reaction temperature. Notably, the PVC gel microlenses produced at this temperature achieve their maximum focal length (ranging from -8 to -20 mm) within approximately 60 s, and they recover their initial state within around 80 s after the power is switched off. This focal length achievement is twice as fast as reported in previous studies on microlenses. It is observed that the reaction temperature significantly influences the solubility of the resin-based raw materials and the homogeneity of the gel. Consequently, these findings open up possibilities for utilizing PVC gel microlenses in novel commercial optics applications, thanks to their desirable properties.

11.
J Am Chem Soc ; 145(20): 11415-11419, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37172099

ABSTRACT

Atomically dispersed catalysts such as single-atom catalysts have been shown to be effective in selectively oxidizing methane, promising a direct synthetic route to value-added oxygenates such as acetic acid or methanol. However, an important challenge of this approach has been that the loading of active sites by single-atom catalysts is low, leading to a low overall yield of the products. Here, we report an approach that can address this issue. It utilizes a metal-organic framework built with porphyrin as the linker, which provides high concentrations of binding sites to support atomically dispersed rhodium. It is shown that up to 5 wt% rhodium loading can be achieved with excellent dispersity. When used for acetic acid synthesis by methane oxidation, a new benchmark performance of 23.62 mmol·gcat-1·h-1 was measured. Furthermore, the catalyst exhibits a unique sensitivity to light, producing acetic acid (under illumination, up to 66.4% selectivity) or methanol (in the dark, up to 65.0% selectivity) under otherwise identical reaction conditions.

12.
Angew Chem Int Ed Engl ; 62(27): e202305568, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37141443

ABSTRACT

Direct synthesis of CH3 COOH from CH4 and CO2 is an appealing approach for the utilization of two potent greenhouse gases that are notoriously difficult to activate. In this Communication, we report an integrated route to enable this reaction. Recognizing the thermodynamic stability of CO2 , our strategy sought to first activate CO2 to produce CO (through electrochemical CO2 reduction) and O2 (through water oxidation), followed by oxidative CH4 carbonylation catalyzed by Rh single atom catalysts supported on zeolite. The net result was CH4 carboxylation with 100 % atom economy. CH3 COOH was obtained at a high selectivity (>80 %) and good yield (ca. 3.2 mmol g-1 cat in 3 h). Isotope labelling experiments confirmed that CH3 COOH is produced through the coupling of CH4 and CO2 . This work represents the first successful integration of CO/O2 production with oxidative carbonylation reaction. The result is expected to inspire more carboxylation reactions utilizing preactivated CO2 that take advantage of both products from the reduction and oxidation processes, thus achieving high atom efficiency in the synthesis.

13.
J Am Chem Soc ; 145(2): 769-773, 2023 01 18.
Article in English | MEDLINE | ID: mdl-36594824

ABSTRACT

Oxidative methane (CH4) carbonylation promises a direct route to the synthesis of value-added oxygenates such as acetic acid (CH3COOH). Here, we report a strategy to realize oxidative CH4 carbonylation through immobilized Ir complexes on an oxide support. Our immobilization approach not only enables direct CH4 activation but also allows for easy separation and reutilization of the catalyst. Furthermore, we show that a key step, methyl migration, that forms a C-C bond, is sensitive to the electrophilicity of carbonyl, which can be tuned by a gentle reduction to the Ir centers. While the as-prepared catalyst that mainly featured Ir(IV) preferred CH3COOH production, a reduced catalyst featuring predominantly Ir(III) led to a significant increase of CH3OH production at the expense of the reduced yield of CH3COOH.


Subject(s)
Iridium , Methane , Iridium/chemistry , Methane/chemistry , Oxidation-Reduction , Catalysis , Oxides
14.
Nat Commun ; 14(1): 352, 2023 01 21.
Article in English | MEDLINE | ID: mdl-36681662

ABSTRACT

DNA-protein crosslinks (DPCs) are pervasive DNA lesions that are induced by reactive metabolites and various chemotherapeutic agents. Here, we develop a technique for the Purification of x-linked Proteins (PxP), which allows identification and tracking of diverse DPCs in mammalian cells. Using PxP, we investigate DPC repair in cells genetically-engineered to express variants of the SPRTN protease that cause premature ageing and early-onset liver cancer in Ruijs-Aalfs syndrome patients. We find an unexpected role for SPRTN in global-genome DPC repair, that does not rely on replication-coupled detection of the lesion. Mechanistically, we demonstrate that replication-independent DPC cleavage by SPRTN requires SUMO-targeted ubiquitylation of the protein adduct and occurs in addition to proteasomal DPC degradation. Defective ubiquitin binding of SPRTN patient variants compromises global-genome DPC repair and causes synthetic lethality in combination with a reduction in proteasomal DPC repair capacity.


Subject(s)
DNA Damage , DNA-Binding Proteins , Animals , Humans , DNA Damage/genetics , DNA Repair/genetics , DNA-Binding Proteins/metabolism , Mammals/genetics , Proteasome Endopeptidase Complex/metabolism
15.
Cancer Gene Ther ; 30(3): 404-413, 2023 03.
Article in English | MEDLINE | ID: mdl-36400965

ABSTRACT

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.


Subject(s)
Triple Negative Breast Neoplasms , Animals , Humans , Mice , Carrier Proteins/metabolism , Cell Line, Tumor , Palmitoyl-CoA Hydrolase/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Triple Negative Breast Neoplasms/metabolism , Female
16.
J Neurosurg ; : 1-10, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36242576

ABSTRACT

OBJECTIVE: Patients with frontal gliomas often experience executive dysfunction (EF-D) before surgery, and the changes in brain plasticity underlying this effect remain obscure. In this study, the authors aimed to assess whole-brain structural and functional alterations by using structural MRI and resting-state functional MRI (rs-fMRI) in frontal glioma patients with or without EF-D. METHODS: Fifty-seven patients with frontal gliomas were admitted prospectively to the authors' institution and assigned to one of two groups: 1) the normal executive function (EF-N) group and 2) the EF-D group, based on patient results for the Trail Making Test, Part B and Stroop Color-Word Test, Part C. Twenty-nine baseline-matched healthy controls were also recruited. All participants underwent multimodal MRI examination. Cortical surface thickness, surface-based resting-state activity (fractional amplitude of low-frequency fluctuation [fALFF] and regional homogeneity [ReHo]), and edge-based network functional connectivity (FC) were measured with FreeSurfer and fMRIPrep. The correlation between altered MRI parameters and executive function (EF) was assessed using Pearson correlation and receiver operating characteristic (ROC) analysis. RESULTS: Demographic characteristics (sex, age, and education level) and clinical characteristics (location, volume, grade of tumor, and preoperative epilepsy) were not significantly different between the groups, but the Karnofsky Performance Scale score was worse in the EF-D group. There was no significant difference in cortical surface thickness between the EF-D and EF-N groups. In both low-grade and high-grade glioma patients the fALFF value (permutation test + threshold-free cluster enhancement, p value after family-wise error correction < 0.05) and ReHo value (t-test, p < 0.001) of the left precuneus cortex in the EF-D group were greater than those in the EF-N group, which were negatively correlated with EF (p < 0.05) and enabled prediction of EF (area under the ROC curve 0.826 for fALFF and 0.855 for ReHo, p < 0.001). Compared with the EF-N group, the FCs between the default mode network (DMN) from DMN node to DMN node (DMN-DMN) and from the DMN to the central executive network (DMN-CEN) in the EF-D group were increased significantly (network-based statistics corrected p < 0.05) and negatively correlated with EF (Pearson correlation, p < 0.05). CONCLUSIONS: Apart from local disruption, the abnormally activated DMN in the resting state is related to EF-D in frontal glioma patients. DMN activity should be considered during preoperative planning and postoperative neurorehabilitation for frontal glioma patients to preserve EF. Clinical trial registration no.: NCT03087838 (ClinicalTrials.gov).

17.
Neurosurg Rev ; 45(5): 3405-3415, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36063221

ABSTRACT

Meningioangiomatosis (MA) is a disease that is extremely rarely reported. Sporadic MA is occasionally combined with meningioma or other lesions (identified as non-pure MA). This retrospective study investigated the difference between pure MA and non-pure MA by exploring clinical manifestations, histopathology characteristics, and outcomes of MA after surgery. We reviewed the medical records of 36 histopathologically confirmed MA patients (18 pure MA and 18 non-pure MA) who received surgery at our institution between 2012 and 2021. We compared differences in demographic, clinical, imaging, pathological features, and surgical outcomes between pure MA and non-pure MA through descriptive statistics. Compared to non-pure MA, pure MA presented with a more prominent male predilection (5:1 vs. 1.57:1, P = 0.264), a higher seizure incidence (83.3% vs 50.0%, P = 0.038), a more seizure type of GTCS (14/15 vs 5/9, P = 0.047), a less prominent enhancement on MRI (27.8% vs 88.9%, P < 0.001) and a preference of temporal and frontal lobe (100% vs 44.4%, P < 0.001). The differences in clinical characteristics between pure MA and non-pure MA demonstrate their disparate biological natures. Pure MA seems to be a non-neoplastic lesion, while non-pure MA is commonly combined with meningioma, which is a neoplastic lesion. A correct differential diagnosis can be achieved via a triad of the type of seizure, the location of lesion and the radiological presentation. MA is curable and the prognosis is excellent as most patients are free of seizure and recurrence after surgical treatment.


Subject(s)
Central Nervous System Vascular Malformations , Meningeal Neoplasms , Meningioma , China , Humans , Magnetic Resonance Imaging , Male , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Meningioma/diagnosis , Meningioma/pathology , Meningioma/surgery , Prognosis , Retrospective Studies , Seizures/etiology
18.
ACS Biomater Sci Eng ; 8(9): 3659-3675, 2022 09 12.
Article in English | MEDLINE | ID: mdl-36037313

ABSTRACT

Cardiac patches are biomaterials that can be used for transplantation and repair of damaged myocardium by combining seed cells with the ability to form cardiomyocytes and suitable scaffold materials. On the one hand, they provide temporary support to the infarcted area, and on the other hand, they repair the damaged myocardium by delivering cells or bioactive factors to integrate with the host, which have gradually become a hot research topic in recent years. This paper summarizes the structural properties of natural myocardium and reviews the recent research progress of cardiac patches, including the seed cells and scaffold materials used in patch preparation, as well as the main methods of scaffold preparation and the structure properties of various scaffolds. In addition, a comprehensive analysis of the problems faced in the clinical implementation of cardiac patches is presented. Finally, we look forward to the development of cardiac patches and point out that precisely tunable anisotropic tissue engineering scaffolds close to natural myocardial tissue will become an important direction for future research.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Biocompatible Materials/therapeutic use , Myocardium , Tissue Engineering/methods , Tissue Scaffolds/chemistry
19.
Front Neurol ; 13: 841521, 2022.
Article in English | MEDLINE | ID: mdl-35812110

ABSTRACT

Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) are a group of diseases associated with small vessel lesions, the former often resulting from the vascular lesion itself, while the latter originating from demyelinating which can damage the cerebral small veins. Clinically, CSVD and MS do not have specific signs and symptoms, and it is often difficult to distinguish between the two from the aspects of the pathology and imaging. Therefore, failure to correctly identify and diagnose the two diseases will delay early intervention, which in turn will affect the long-term functional activity for patients and even increase their burden of life. This review has summarized recent studies regarding their similarities and difference of the clinical manifestations, pathological features and imaging changes in CSVD and MS, which could provide a reliable basis for the diagnosis and differentiation of the two diseases in the future.

20.
ACS Omega ; 7(28): 24895-24902, 2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35874234

ABSTRACT

Trace hydrogen detection plays an important role in the safety detection of lithium-ion batteries (LIBs) due to the generation and leakage of trace hydrogen in the early stage of LIBs damage. In this work, an amperometric hydrogen sensor based on solid polymer electrolyte was reported. The sandwich device structure was realized, which could directly diffuse the gas from both sides to the three-phase interface (gas/electrode/electrolyte) to participate in the reaction through the optimal design of the gas diffusion path. Then, platinum nanoparticles (Pt-NPs) were loaded on the metal foam by electroplating, and the porous electrode was filled with solid polymer electrolyte. A sensor with high specific surface area, high catalytic activity, and high sensitivity was obtained. Finally, the hydrogen oxidation reaction (HOR) mechanism of the platinum-loaded (Pt-loaded) titanium foam (Ti foam) electrode under both anaerobic and aerobic conditions was verified, and the properties of the sensor was evaluated. The hydrogen sensor with a "sandwich" structure has the advantages of high sensitivity, good stability, low detection limit and low cost, which provides a technical solution for the safety and real-time monitoring of LIBs.

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