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1.
Adv Sci (Weinh) ; : e2404213, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981036

RESUMO

Recently emerging lithium ternary chlorides have attracted increasing attention for solid-state electrolytes (SSEs) due to their favorable combination between ionic conductivity and electrochemical stability. However, a noticeable discrepancy in Li-ion conductivity persists between chloride SSEs and organic liquid electrolytes, underscoring the need for designing novel chloride SSEs with enhanced Li-ion conductivity. Herein, an intriguing trigonal structure (i.e., Li3SmCl6 with space group P3112) is identified using the global structure searching method in conjunction with first-principles calculations, and its potential for SSEs is systematically evaluated. Importantly, the structure of Li3SmCl6 exhibits a high ionic conductivity of 15.46 mS cm-1 at room temperature due to the 3D lithium percolation framework distinct from previous proposals, associated with the unique in-plane cation ordering and stacking sequences. Furthermore, it is unveiled that Li3SmCl6 possesses a wide electrochemical window of 0.73-4.30 V vs Li+/Li and excellent chemical interface stability with high-voltage cathodes. Several other Li3MCl6 (M = Er, and In) materials with isomorphic structures to Li3SmCl6 are also found to be potential chloride SSEs, suggesting the broader applicability of this structure. This work reveals a new class of ternary chloride SSEs and sheds light on strategy for structure searching in the design of high-performance SSEs.

2.
Proc Natl Acad Sci U S A ; 121(23): e2318843121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38805277

RESUMO

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Mutação , Glioma/genética , Glioma/cirurgia , Glioma/patologia , Isocitrato Desidrogenase/genética , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Espectrometria de Massas em Tandem/métodos , Glutaratos/metabolismo , Espectrometria de Massas/métodos , Ácido Glutâmico/metabolismo , Ácido Glutâmico/genética
3.
Environ Sci Pollut Res Int ; 31(13): 19961-19973, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368299

RESUMO

Mixed carbon sources have been developed for denitrification to eliminate the "carbon dependency" problem of single carbon. The metabolic correlation between different carbon sources is significant as guidance for the development of novel mixed carbon sources. In this study, to explore the metabolic similarity of denitrifying carbon sources, we selected alcohols (methanol, ethanol, and glycerol) and saccharide carbon sources (glucose, sucrose, and starch). Batch denitrification experiments revealed that methanol-acclimated sludge improved the denitrification rate of both methanol (14.42 mg-N/gMLVSS*h) and ethanol (9.65 mg-N/gMLVSS*h), whereas ethanol-acclimated sludge improved the denitrification rate of both methanol (7.80 mg-N/gMLVSS*h) and ethanol (22.23 mg-N/gMLVSS*h). In addition, the glucose-acclimated sludge and sucrose-acclimated sludge possibly improved the denitrification rate of glucose and sucrose, and the glycerol-acclimated sludge improved the denitrification rate of volatile fatty acids (VFAs), alcohols, and saccharide carbon sources. Functional gene analysis revealed that methanol, ethanol, and glycerol exhibited active alcohol oxidation and glyoxylate metabolism, and glycerol, glucose, and sucrose exhibited active glycolysis metabolism. This indicated that the similarity in the denitrification metabolism of these carbon sources was based on functional gene similarity, and glycerol-acclimated sludge exhibited the most diverse metabolism, which ensured its good denitrification effect with other carbon sources.


Assuntos
Carbono , Metanol , Carbono/metabolismo , Esgotos , Glicerol , Reatores Biológicos , Etanol/metabolismo , Glucose , Sacarose , Desnitrificação , Nitrogênio
5.
Environ Res ; 238(Pt 1): 117142, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37739155

RESUMO

In wastewater treatment plants (WWTPs), aeration is vital for microbial oxygen needs. To achieve carbon neutrality, optimizing aeration for energy and emissions reduction is imperative. Machine learning (ML) is used in wastewater treatment to reveal complex rules in large data sets has become a trend. In this vein, the present paper proposes an aeration optimization approach based on the extreme gradient boosting-bidirectional long short-term memory (XGB-Bi-LSTM) model via the online monitoring of oxygen transfer efficiency (OTE) and oxygen uptake rate (OUR), thus allowing WWTPs to conserve energy and reduce indirect carbon emissions. The approach uses gain algorithm of XGB to calculate the importance of features and identify important parameters, and then uses Bi-LSTM to predict the target with important parameters as features. Operational data from a WWTP in Suzhou, China, is employed to train and test the approach, the performance of which is compared with ML models suitable for regression prediction tasks (XGB, random forest, light gradient boosting machine, gradient boosting and LSTM). Experimental results show the approach requires only a small number of input parameters to achieve good performance and outperforms other machine-learning models. When OTE and dissolved oxygen (DO) are used as features to predict the alpha factor (αF; since diffusers were used, multiply by the pollution factor F), the R-squared (R2) is 0.9977, the root mean square error (RMSE) is 0.0043, the mean absolute percentage error (MAPE) is 0.0069 and the median absolute error (MedAE) is 0.0032. When the predicted αF and the OUR are used as features to predict the air flow rate of an aeration unit, the R2 is 0.9901, the RMSE is 3.6150, the MAPE is 0.0209 and the MedAE is 1.5472. Using our optimized aeration approach, the energy consumption can be reduced by 23%.


Assuntos
Oxigênio , Purificação da Água , Oxigênio/análise , Águas Residuárias , Purificação da Água/métodos , Algoritmos , Carbono
6.
NPJ Precis Oncol ; 7(1): 97, 2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37741941

RESUMO

Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence.

7.
Int J Surg ; 109(12): 4062-4072, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755386

RESUMO

BACKGROUND: The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus. MATERIALS AND METHODS: In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center. RESULTS: The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome. CONCLUSIONS: The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.


Assuntos
Neoplasias Encefálicas , Glioma , Hidrocefalia , Glândula Pineal , Pinealoma , Terceiro Ventrículo , Masculino , Feminino , Humanos , Adulto , Pinealoma/cirurgia , Pinealoma/complicações , Pinealoma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Glândula Pineal/cirurgia , Glândula Pineal/patologia , Glioma/cirurgia , Ventriculostomia/efeitos adversos , Ventriculostomia/métodos , Terceiro Ventrículo/patologia , Terceiro Ventrículo/cirurgia , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Neoplasias Encefálicas/cirurgia
8.
BMC Cancer ; 23(1): 544, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316802

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). METHODS: PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). RESULTS: Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. CONCLUSIONS: Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Bevacizumab/efeitos adversos , Qualidade de Vida , Encéfalo
10.
Cell Mol Neurobiol ; 43(6): 2975-2987, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37081231

RESUMO

Gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. FAM64A, a cell cycle-related gene, has been found to promote cell proliferation in various tumors, including gliomas. However, the regulatory mechanism and clinical significance of FAM64A in gliomas remain unclear. In this study, we investigated FAM64A expression in gliomas with different grades and constructed FAM64A silenced cell lines to study its functions. Our results demonstrated that FAM64A was highly expressed in glioblastoma (P < 0.001) and associated with a poor prognosis (P < 0.001). Expression profiles at the single-cell resolution indicated FAM64A could play a role in a cell-cycle-dependent way to promote glioma cell proliferation. We further observed that FAM64A silencing in glioma cells resulted in disrupted proliferation and migration ability, and increased cell accumulation in the G2/M phase (P = 0.034). Additionally, TGF-ß signaling upregulates FAM64A expression, and SMAD4 and FAM64A co-localize in high-grade glioma tissues. We found FAM64A knockdown inhibited TGF-ß-induced epithelial-mesenchymal transition in glioma. Our findings suggest that FAM64A could serve as a diagnostic and therapeutic target in gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/patologia , Neoplasias Encefálicas/patologia , Ciclo Celular/genética , Proliferação de Células/genética , Divisão Celular , Transição Epitelial-Mesenquimal/genética , Fator de Crescimento Transformador beta/metabolismo , Movimento Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
11.
Neurol Res ; 45(4): 354-362, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36509700

RESUMO

OBJECTIVE: Neuroendoscopic resection via supracerebellar infratentorial (SCIT) approach is adequate for some indicated pineal region tumors with the natural infratentorial corridor. We described this full endoscopic approach through a modified 'head-up' park-bench position to facilitate the procedure. METHODS: We reviewed the clinical and radiological data of four patients with pineal region lesions who underwent pure endoscopic tumor resection through the SCIT approach with this modified position. The related literature concerning fully endoscopic pineal region tumor resection was also reviewed. RESULTS: This cohort included four patients with pineal region tumors. External ventricular drainage (Ommaya reservoir) was performed in three patients with hydrocephalus in advance. The average tumor volume was 19.2 ± 17.2 cm3. Pathological examination confirmed two mixed germinomas, one glioblastoma multiforme, and one hemangioblastoma. Gross total resection (GTR) was achieved in all patients, and all patients recovered well without neurological deficits or surgical complications. Hydrocephalus was relieved among all patients. CONCLUSIONS: The pure endoscopic SCIT approach could enable safe and effective resection of pineal region tumors, even for relatively large lesions. The endoscope could provide a panoramic view and illumination of the deep-seated structures. Compared with the sitting position, this modified ergonomic position could be implemented easily.


Assuntos
Neoplasias Encefálicas , Neuroendoscopia , Glândula Pineal , Pinealoma , Humanos , Postura Sentada , Procedimentos Neurocirúrgicos/métodos , Pinealoma/diagnóstico por imagem , Pinealoma/cirurgia , Pinealoma/patologia , Glândula Pineal/diagnóstico por imagem , Glândula Pineal/cirurgia , Glândula Pineal/patologia , Neuroendoscopia/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia
12.
Environ Res ; 219: 115004, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481369

RESUMO

Aiming for treating decentralized domestic wastewater in rural China, this study evaluates the effects of ceramsite size and structure, and water recirculation parameters, upon the performance of recirculating biofilter (RBF). RBF shows stable capability of chemical oxygen demand (COD) remediation and ammonia nitrification. In addition, the microbial flora and structures of the various layers in the system are analyzed via high-throughput sequencing in order to study the microbial diversity. The results indicate that while the ceramic particle size has no significant influence on the COD remediation capacity, the ceramics with smaller particle sizes exhibit better ammonia nitrogen (NH4+-N) removal ability, with a first-order linear relationship between the influent ammonia nitrogen load and the effluent NH4+-N concentration in RBF (R2 > 0.64). An increased hydraulic load and intermittent operation are shown to deteriorate the water quality with respect to NH4+-N, while an increased recirculation ratio increases the removal rate of NH4+-N from the effluent. Further, the water distribution time has a stronger effect upon the NH4+-N concentration in the effluent than does the recirculation ratio. Moreover, the microbial structure of the multi-layer recirculating trickle biofilter varies significantly during the process. The results indicate that a high recirculation ratio, long water distribution time, and multi-layer structure will be beneficial for improving the pollutant treatment capacity of RBF.


Assuntos
Amônia , Esgotos , Reatores Biológicos , Águas Residuárias , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos
13.
Environ Int ; 170: 107598, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36395558

RESUMO

Characterizing the molecular mechanism through which different carbon sources affect the denitrification process would provide a basis for the proper selection of carbon sources, thus avoiding excessive carbon source dosing and secondary pollution while also improving denitrification efficiency. Here, we selected Thauera linaloolentis as a model organism of denitrification, whose genomic information was elucidated by draft genome sequencing and KEGG annotations, to investigate the growth kinetics, denitrification performances and characteristics of metabolic pathways under diverse carbon source conditions. We reconstructed a metabolic network of Thauera linaloolentis based on genomic analysis to help develop a systematic method of researching electron pathways. Our findings indicated that carbon sources with simple metabolic pathways (e.g., ethanol and sodium acetate) promoted the reproduction of Thauera linaloolentis, and its maximum growth density reached OD600 = 0.36 and maximum specific growth rate reached 0.145 h-1. These carbon sources also accelerated the denitrification process without the accumulation of intermediates. Nitrate could be reduced completely under any carbon source condition; but in the "glucose group", the maximum accumulation of nitrite was 117.00 mg/L (1.51 times more than that in the "ethanol group", which was 77.41 mg/L), the maximum accumulation of nitric oxide was 363.02 µg/L (7.35 times more than that in the "ethanol group", which was 49.40 µg/L), and the maximum accumulation of nitrous oxide was 22.58 mg/L (26.56 times more than that in the "ethanol group", which was 0.85 mg/L). Molecular biological analyses demonstrated that diverse types of carbon sources directly induced different carbon metabolic activities, resulting in variations in electron generation efficiency. Furthermore, the activities of the electron transport system were positively correlated with different carbon metabolic activities. Finally, these differences were reflected in the phenomenon of electronic competition between denitrifying reductases. Thus we concluded that this was the main molecular mechanism through which the carbon source type affected the denitrification process. In brief, carbon sources with simple metabolic pathways induced higher efficiency of electron generation, transfer, and competition, which promoted rapid proliferation and complete denitrification; otherwise Thauera linaloolentis would grow slowly and intermediate products would accumulate seriously. Our study established a method to evaluate and optimize carbon source utilization efficiency based on confirmed molecular mechanisms.


Assuntos
Carbono , Elétrons , Eletrônica
14.
Front Immunol ; 13: 1039862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439151

RESUMO

Purpose: The systemic immune-inflammation index (SII) has been considered a novel prognostic biomarker in several types of lymphoma. Our aims were to determine the best statistical relationship between pretreatment SII and survival and to combination of SII and the Memorial Sloan Kettering Cancer Center model (MSKCC) to derive the best prognostic mode in primary central nervous system lymphoma (PCNSL). Methods: Pretreatment SII and clinical data in 174 newly diagnosed PCNSL patients were included from two retrospective discovery cohorts (n = 128) and one prospective validation cohort (n = 46). A generalized additive model, Kaplan-Meier curve, and Cox analysis were performed. The high risk versus low risk of SII-MSKCC for the PCNSL cutoff point (0-1 vs. 2-4) was determined by the minimum P-value approach. Results: The SII showed a U-shaped relationship with the risk of overall survival (OS; P = 0.006). The patients with low SII or high SII had poorer OS and progression-free survival (PFS) than those with median SII. For PFS and OS, SII-MSKCC was a better predictor than MSKCC alone. The area under the receiver operating characteristic curve of the SII-MSKCC score was 0.84 for OS and 0.78 for PFS in the discovery cohorts. The predictive value of the SII-MSKCC score (OS, 0.88; PFS, 0.95) was verified through the validation cohort. Multivariable Cox analysis and Kaplan-Meier curve showed excellent performance for SII-MSKCC, with significant separation of two groups and better performance than MSKCC alone. Conclusions: We propose a new prognostic model using SII, age, and Karnofsky score that outperforms MSKCC alone and enables individualized estimates of patient outcome.


Assuntos
Linfoma , Neutrófilos , Humanos , Prognóstico , Neutrófilos/patologia , Estudos Retrospectivos , Inflamação/patologia , Linfoma/diagnóstico , Linfoma/patologia , Sistema Nervoso Central/patologia
15.
Bioresour Technol ; 364: 128044, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182014

RESUMO

Solid-phase denitrification is a promising alternative denitrification technology when facing a shortage of carbon sources. Nevertheless, it is still unclear whether there is a certain interaction between the denitrification process and the carbon release process in a solid-phase denitrification system. In this study, the concept of "Self-adaptation" was proposed for the relationship between denitrification and carbon release. At various influent nitrate loads, the PCL-supported denitrification system achieved an average nitrate removal rate of over 90.59 ± 7.01 % and a maximum denitrification rate of 0.67 ± 0.06 gN/(L·d). Microorganisms can spontaneously regulate the carbon release rate of PCL in response to changes in influent nitrate load, demonstrating "self-adaptation" of the PCL-supported solid-phase denitrification system. Regulation of carbon release rate via the "Self-adaptation" was achieved by changes in extracellular depolymerase activity. Acidovorax_sp. played a key role in "Self-adaptation", for its function of both denitrification and PCL degradation.

16.
EPMA J ; 13(3): 499-517, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36061828

RESUMO

Background/aims: Predicting the clinical outcomes of primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) to methotrexate-based combination immunochemotherapy treatment in advance and therefore administering the tailored treatment to the individual is consistent with the principle of predictive, preventive, and personalized medicine (PPPM/3PM). The red blood cell distribution width (RDW) has been reported to be associated with the clinical outcomes of multiple cancer. However, its prognostic role in PCNS-DLBCL is yet to be evaluated. Therefore, we aimed to effectively stratify PCNS-DLBCL patients with different prognosis in advance and early identify the patients who were appropriate to methotrexate-based combination immunochemotherapy based on the pretreatment level of RDW and a clinical prognostic model. Methods: A prospective-retrospective, multi-cohort study was conducted from 2010 to 2020. We evaluated RDW in 179 patients (retrospective discovery cohorts of Huashan Center and Renji Center and prospective validation cohort of Cancer Center) with PCNS-DLBCL treated with methotrexate-based combination immunochemotherapy. A generalized additive model with locally estimated scatterplot smoothing was used to identify the relationship between pretreatment RDW levels and clinical outcomes. The high vs low risk of RDW combined with MSKCC score was determined by a minimal P-value approach. The clinical outcomes in different groups were then investigated. Results: The pretreatment RDW showed a U-shaped relationship with the risk of overall survival (OS, P = 0.047). The low RDW (< 12.6) and high RDW (> 13.4) groups showed significantly worse OS (P < 0.05) and progression-free survival (PFS; P < 0.05) than the median group (13.4 > RDW > 12.6) in the discovery and validation cohort, respectively. RDW could predict the clinical outcomes successfully. In the discovery cohort, RDW achieved the area under the receiver operating characteristic curve (AUC) of 0.9206 in predicting the clinical outcomes, and the predictive value (AUC = 0.7177) of RDW was verified in the validation cohort. In addition, RDW combined with MSKCC predictive model can distinguish clinical outcomes with the AUC of 0.8348 for OS and 0.8125 for PFS. Compared with the RDW and MSKCC prognosis variables, the RDW combined with MSKCC scores better identified a subgroup of patients with favorable long-term survival in the validation cohort (P < 0.001). RDW combined MSKCC score remained to be independently associated with clinical outcomes by multivariable analysis. Conclusions: Based on the pretreatment RDW and MSKCC scores, a novel predictive tool was established to stratify PCNS-DLBCL patients with different prognosis effectively. The predictive model developed accordingly is promising to judge the response of PCNS-DLBCL to methotrexate-based combination immunochemotherapy treatment. Thus, hematologists and oncologists could tailor and adjust therapeutic modalities by monitoring RDW in a prospective rather than the reactive manner, which could save medical expenditures and is a key concept in 3PM. In brief, RDW combined with MSKCC model could serve as an important tool for predicting the response to different treatment and the clinical outcomes for PCNS-DLBCL, which could conform with the principles of predictive, preventive, and personalized medicine. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00290-5.

17.
Front Pharmacol ; 13: 911760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774612

RESUMO

Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 µM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 µM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.

18.
Comput Math Methods Med ; 2022: 9448144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242216

RESUMO

Based on alterations in gene expression associated with the production of glycolysis and cholesterol, this research classified glioma into prognostic metabolic subgroups. In this study, data from the CGGA325 and The Cancer Genome Atlas (TCGA) datasets were utilized to extract single nucleotide variants (SNVs), RNA-seq expression data, copy number variation data, short insertions and deletions (InDel) mutation data, and clinical follow-up information from glioma patients. Glioma metabolic subtypes were classified using the ConsensusClusterPlus algorithm. This study determined four metabolic subgroups (glycolytic, cholesterogenic, quiescent, and mixed). Cholesterogenic patients had a higher survival chance. Genome-wide investigation revealed that inappropriate amplification of MYC and TERT was associated with improper cholesterol anabolic metabolism. In glioma metabolic subtypes, the mRNA levels of mitochondrial pyruvate carriers 1 and 2 (MPC1/2) presented deletion and amplification, respectively. Differentially upregulated genes in the glycolysis group were related to pathways, including IL-17, HIF-1, and TNF signaling pathways and carbon metabolism. Downregulated genes in the glycolysis group were enriched in terpenoid backbone biosynthesis, nitrogen metabolism, butanoate metabolism, and fatty acid metabolism pathway. Cox analysis of univariate and multivariate survival showed that risks of glycolysis subtypes were significantly higher than other subtypes. Those results were validated in the CGGA325 dataset. The current findings greatly contribute to a comprehensive understanding of glioma and personalized treatment.


Assuntos
Neoplasias Encefálicas/classificação , Glioma/classificação , Algoritmos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Colesterol/biossíntese , Colesterol/genética , Biologia Computacional , Bases de Dados Genéticas/estatística & dados numéricos , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Glicólise/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Sci Total Environ ; 818: 151751, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-34843777

RESUMO

Overall understanding of microbial community structure in activated sludge (AS) system at regional level is of great significance for operation regulation of wastewater treatment plants (WWTPs). In this study, 110 AS samples from 21 cities in different Chinese regions were analyzed based on high-throughput 16S ribosomal DNA (rDNA) sequencing to explore effects of different regions on microbial community structure. Results showed that the regions with different characteristics (south and north, coastal and inland, high GDP and low GDP) had great impact on AS bacterial community in China. Core bacterial communities (101 OTUs) in south China were more abundant than those in north China (49 OTUs), and many core species in south China were associated with nutrient removal. Coastal WWTPs possessed unique bacterial communities due to the influence of marine bacteria. Phyla Chloroflexi and Acidobacteria were observed to be main biomarkers in coastal WWTPs. Compared with low GDP regions, more diverse microbial community and effective wastewater treatment were discovered in high GDP regions, and environmental factor analysis suggested that they were mainly correlated with high capacity and influent TP in the WWTPs. ß nearest taxon index (ßNTI) analysis showed that microbial community assembly in the analyzed AS samples was dominated by deterministic factors (70.67%) and influent quality was observed to be main factor.


Assuntos
Microbiota , Purificação da Água , DNA Ribossômico , Microbiota/genética , RNA Ribossômico 16S/genética , Esgotos/microbiologia , Águas Residuárias/química
20.
Front Nutr ; 9: 1103838, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36704793

RESUMO

Introduction: The production of the large yellow croaker has seasonal and regional characteristics, which is typically preserved on ice, possibly leading to its deterioration in a short time. Therefore, in this study, we focused on the effect of temperature fluctuation on the quality changes of the large yellow croaker during frozen storage. Methods: In this experiment, the large yellow croaker was soaked in a low-salt solution, and physical and chemical properties, water-holding capacity, color, and protein characteristics of the muscle were investigated after repeated freeze-thaw (F-T) cycles and frozen storage. Results and discussion: The results show the deterioration of muscle quality of large yellow croaker after low-salt treatment was lower than that of the salt-free soaking group. The salting treatment significantly (P < 0.05) enhanced the yield of large yellow croaker, which was 24.3% greater than the salt-free soaking group after 6 weeks of frozen storage. The microstructure of the salted muscle was more stable and maintained its cellular structure after F-T cycles and frozen storage. The b* value of the salt-free soaking group increased from b* value of the low-salt soaking group decreased from acceptable range. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicates the content of 17 kDa peptide decreased in the low-salt soaking group, and the peptides at 21 and 24 kDa increased during frozen storage. The results of the present study provide guidance for the optimal processing, transport, and storage of large yellow croaker, but the effect of salting on lipid oxidation and protein oxidation requires further study.

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