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1.
Blood ; 142(11): 973-988, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37235754

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Up to 40% of patients with DLBCL display refractory disease or relapse after standard chemotherapy treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), leading to significant morbidity and mortality. The molecular mechanisms of chemoresistance in DLBCL remain incompletely understood. Using a cullin-really interesting new gene (RING) ligase-based CRISPR-Cas9 library, we identify that inactivation of the E3 ubiquitin ligase KLHL6 promotes DLBCL chemoresistance. Furthermore, proteomic approaches helped identify KLHL6 as a novel master regulator of plasma membrane-associated NOTCH2 via proteasome-dependent degradation. In CHOP-resistant DLBCL tumors, mutations of NOTCH2 result in a protein that escapes the mechanism of ubiquitin-dependent proteolysis, leading to protein stabilization and activation of the oncogenic RAS signaling pathway. Targeting CHOP-resistant DLBCL tumors with the phase 3 clinical trial molecules nirogacestat, a selective γ-secretase inhibitor, and ipatasertib, a pan-AKT inhibitor, synergistically promotes DLBCL destruction. These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Linfoma Difuso de Grandes Células B , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Ubiquitina , Proteômica , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/uso terapêutico , Vincristina , Ciclofosfamida , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Prednisona , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor Notch2/genética
2.
Small ; : e2400828, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693068

RESUMO

Efficient support materials are crucial for maximizing the efficacy of nanomaterials in various applications such as energy storage, drug delivery, catalysis, and environmental remediation. However, traditional supports often hinder nanomaterial performance due to their high weight ratio and limited manageability, leading to issues like tube blocking and secondary pollution. To address this, a novel grapefruit-inspired polymeric capsule (GPC) as a promising carrier platform is introduced. The millimeter-scale GPC features a hydrophilic shell and an internal hierarchical microstructure with 80% void volume, providing ample space for encapsulating diverse nanomaterials including metals, polymers, metal-organic frameworks, and silica. Through liquid-phase bottom-up methods, it is successfully loaded Fe2O3, SiO2, polyacrylic acid, and Prussian blue nanomaterials onto the GPC, achieving high mass ratio (1776, 488, 898, and 634 wt.%, respectively). The GPC shell prevents nanomaterial leakage and the influx of suspended solids, while its internal framework enhances structural stability and mass transfer rates. With long-term storage stability, high carrying capacity, and versatile applicability, the GPC significantly enhances the field applicability of nanomaterials.

3.
Crit Care Med ; 52(3): e110-e120, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38381018

RESUMO

OBJECTIVES: The limitations of current early warning scores have prompted the development of deep learning-based systems, such as deep learning-based cardiac arrest risk management systems (DeepCARS). Unfortunately, in South Korea, only two institutions operate 24-hour Rapid Response System (RRS), whereas most hospitals have part-time or no RRS coverage at all. This study validated the predictive performance of DeepCARS during RRS operation and nonoperation periods and explored its potential beyond RRS operating hours. DESIGN: Retrospective cohort study. SETTING: In this 1-year retrospective study conducted at Yonsei University Health System Severance Hospital in South Korea, DeepCARS was compared with conventional early warning systems for predicting in-hospital cardiac arrest (IHCA). The study focused on adult patients admitted to the general ward, with the primary outcome being IHCA-prediction performance within 24 hours of the alarm. PATIENTS: We analyzed the data records of adult patients admitted to a general ward from September 1, 2019, to August 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance evaluation was conducted separately for the operational and nonoperational periods of the RRS, using the area under the receiver operating characteristic curve (AUROC) as the metric. DeepCARS demonstrated a superior AUROC as compared with the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), both during RRS operating and nonoperating hours. Although the MEWS and NEWS exhibited varying performance across the two periods, DeepCARS showed consistent performance. CONCLUSIONS: The accuracy and efficiency for predicting IHCA of DeepCARS were superior to that of conventional methods, regardless of whether the RRS was in operation. These findings emphasize that DeepCARS is an effective screening tool suitable for hospitals with full-time RRS, part-time RRS, and even those without any RRS.


Assuntos
Aprendizado Profundo , Parada Cardíaca , Adulto , Humanos , Quartos de Pacientes , Estudos Retrospectivos , Hospitais Universitários , Gestão de Riscos
4.
Small ; 19(48): e2305247, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37518852

RESUMO

The development of efficient adsorbents for the practical recovery of precious metals from electronic waste is vital to advanced energy/environment industries. Ti3 C2 Tx MXene-based materials are promising adsorbents for aqueous environments; however, the highly defective and super hydrophilic nature of the MXene surface hinders its practical applications. Here, we report that nitrogen-doped MXene (N-MXene) nanosheet stacks, prepared via high-energy planetary ball milling under N2 purging, exhibited a long-term stable and excellent recovery capability for Au and Ag ions via the nitrogenation of defective vacancies. Notably, these microscale nanosheets could facilitate the sustainable production of Au and Ag from secondary sources, exhibiting a high recovery rate and capability (1198 mg g-1 for Au and 1528 mg g-1 for Ag), long-term stable storability (21 d), and high selectivity (Kd of 1.67 × 106 for Au and 2.07 × 107 for Ag). Furthermore, the reversible redox chemistry of N-MXene facilitated its repeated use in adsorption/desorption cycles.

5.
BMC Pediatr ; 23(1): 525, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872515

RESUMO

BACKGROUND: Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician's ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). METHODS: We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. RESULTS: A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P < 0.05). Our proposed model, tested on a dataset from March 4, 2019, to March 4, 2022. The mean AUROC of our proposed model for IMV support prediction performance demonstrated 0.861 (95%CI, 0.853-0.869). It is superior to conventional approaches, such as newborn early warning score systems (NEWS), Random Forest, and eXtreme gradient boosting (XGBoost) with 0.611 (95%CI, 0.600-0.622), 0.837 (95%CI, 0.828-0.845), and 0.0.831 (95%CI, 0.821-0.845), respectively. The highest AUPRC value is shown in the proposed model at 0.327 (95%CI, 0.308-0.347). The proposed model performed more accurate predictions as gestational age decreased. Additionally, the model exhibited the lowest alarm rate while maintaining the same sensitivity level. CONCLUSION: Deep learning approaches can help accurately standardize the prediction of invasive mechanical ventilation for neonatal patients and facilitate advanced neonatal care. The results of predictive, recall, and alarm performances of the proposed model outperformed the other models.


Assuntos
Unidades de Terapia Intensiva Neonatal , Respiração Artificial , Lactente , Humanos , Recém-Nascido , Respiração Artificial/métodos , Peso ao Nascer , Inteligência Artificial , Registros Eletrônicos de Saúde
6.
Proc Natl Acad Sci U S A ; 117(11): 6092-6102, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32127472

RESUMO

The KLHL14 gene acquires frequent inactivating mutations in mature B cell malignancies, especially in the MYD88L265P, CD79B mutant (MCD) genetic subtype of diffuse large B cell lymphoma (DLBCL), which relies on B cell receptor (BCR) signaling for survival. However, the pathogenic role of KLHL14 in DLBCL and its molecular function are largely unknown. Here, we report that KLHL14 is in close proximity to the BCR in the endoplasmic reticulum of MCD cell line models and promotes the turnover of immature glycoforms of BCR subunits, reducing total cellular BCR levels. Loss of KLHL14 confers relative resistance to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and promotes assembly of the MYD88-TLR9-BCR (My-T-BCR) supercomplex, which initiates prosurvival NF-κB activation. Consequently, KLHL14 inactivation allows MCD cells to maintain NF-κB signaling in the presence of ibrutinib. These findings reinforce the central role of My-T-BCR-dependent NF-κB signaling in MCD DLBCL and suggest that the genetic status of KLHL14 should be considered in clinical trials testing inhibitors of BTK and BCR signaling mediators in DLBCL.


Assuntos
Proteínas de Transporte/genética , Genes Supressores de Tumor , Linfoma Difuso de Grandes Células B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo , Adenina/análogos & derivados , Antígenos CD79/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Linfoma Difuso de Grandes Células B/patologia , Mutagênese Sítio-Dirigida , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Piperidinas , Proteólise , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
7.
Int J Mol Sci ; 24(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37569446

RESUMO

This study investigated the protective effect of glutathione (GSH), an antioxidant drug, against doxorubicin (DOX)-induced cardiotoxicity. Human cardiac progenitor cells (hCPCs) treated with DOX (250 to 500 nM) showed increased viability and reduced ROS generation and apoptosis with GSH treatment (0.1 to 1 mM) for 24 h. In contrast to the 500 nM DOX group, pERK levels were restored in the group co-treated with GSH and suppression of ERK signaling improved hCPCs' survival. Similarly to the previous results, the reduced potency of hCPCs in the 100 nM DOX group, which did not affect cell viability, was ameliorated by co-treatment with GSH (0.1 to 1 mM). Furthermore, GSH was protected against DOX-induced cardiotoxicity in the in vivo model (DOX 20 mg/kg, GSH 100 mg/kg). These results suggest that GSH is a potential therapeutic strategy for DOX-induced cardiotoxicity, which performs its function via ROS reduction and pERK signal regulation.

8.
J Environ Manage ; 328: 116971, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36516708

RESUMO

For the in-situ remediation of the contaminated subsurface environment, the injection of nutrients and microorganisms changes chemical and physical conditions, which control the delivery and immobilization of microorganisms. We investigated the injection strategy for effective bacterial delivery in a bioaugmentation scheme by controlling ionic strength (IS) and pore-water velocity (v). A set of bacterial transport tests was conducted using the saturated sand column to mimic the saturated subsurface environment. The effectiveness of the injection strategies was evaluated by applying solutions with different ionic strengths into the sand column with different pore-water velocities. The deposition and delivery of bacteria through the sand column were analyzed using the first-order deposition model. The deposition and delivery of bacteria injected by various strategies were numerically simulated considering the variable deposition rate. The breakthrough curves from column experiments revealed that the bacterial deposition on the sand surface was increased by an increase in the ionic strength and by a decrease in the pore-water velocities. The rates of bacterial deposition (k1) on sand could be determined as a function of ionic strength and pore-water velocity, and it was applicable to simulate the delivery of bacteria under dynamic groundwater conditions. The numerical case study considering various injection strategies showed that the nutrient concentration controlled the bacterial delivery to the target area more significantly than the injection flow rate. Injection of bacterial solution with lower nutrient concentration could be increased the deposited bacterial concentration at the target point (Stp) by 6.2-7.1 times higher. Short pulse injection with a high injection rate decreased Stp by 67-78%. The efficiency of bacterial delivery (Ed) could be increased three times higher by lowering nutrient concentration in the injection solution. The process of evaluating the efficiency of bacterial delivery could be a prominent approach to determining the injection strategy for in-situ remediation considering variable conditions of a contaminated site.


Assuntos
Areia , Água , Água/química , Concentração Osmolar , Porosidade , Dióxido de Silício
9.
Environ Monit Assess ; 195(12): 1465, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37957404

RESUMO

Gongji Stream flows into Lake Uiam, a potable water source for the capital region of Chuncheon, South Korea. Algal blooms often occur downstream of the Gongji stream in combination with drastic flow rate variations. Downstream water quality may also be affected by Yaksa stream. Yaksa stream joins Gongji stream before it reaches Uiam Lake, which is a drinking water source for the city. Limited data exists on the Yaksa stream water quality. Therefore, water quality parameters (pH, electrical conductivity (EC), biological oxygen demand (BOD), total nitrogen (T-N), total phosphorous (T-P), chlorophyll-a (Chl-a), total coliforms, and Escherichia coli (E. coli) concentration) were sampled from Gongji (at sites GJ1 and GJ2) and Yaksa (at sites YS1 and YS2) streams from May to September, 2022. The results revealed the overall water quality of both streams was good (BOD = 0.27-3.66 mg/L; TP = 0.003-0.074 mg/L), except on August 3. On August 3, the concentrations of BOD, TP, total coliforms, and E. coli were elevated, with the highest concentrations in samples from GJ2. The recent heavy rainfall potentially caused sewage inflows near GJ2. The correlation analysis revealed positive linear relationships in the 1-day cumulative precipitation with BOD (r = 0.503), total coliforms (r = 0.547), and TP (r = 0.814). The Yaksa stream may be an Anabaena sp. source, which contaminated samples from YS1, YS2, and GJ2, but not at GJ1 (upstream of the tributary).


Assuntos
Monitoramento Ambiental , Qualidade da Água , Estações do Ano , Escherichia coli , Clorofila A/análise , Fósforo/análise
10.
Am J Physiol Cell Physiol ; 322(3): C370-C381, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35080922

RESUMO

Cannabis usage has steadily increased as acceptance is growing for both medical and recreational reasons. Medical cannabis is administered for treatment of chronic pain based on the premise that the endocannabinoid system signals desensitize pain sensor neurons and produce anti-inflammatory effects. The major psychoactive ingredient of cannabis is Δ9-tetrahydrocannabinol (THC) that signals mainly through cannabinoid receptor-1 (CBr), which is also present on nonneuron cells including blood platelets of the circulatory system. In vitro, CBr-mediated signaling has been shown to acutely inhibit platelet activation downstream of the platelet collagen receptor glycoprotein (GP)VI. The systemic effects of chronic THC administration on platelet activity and function remain unclear. This study investigates the effects of chronic THC administration on platelet function using a nonhuman primate (NHP) model. Our results show that female and male NHPs consuming a daily THC edible had reduced platelet adhesion, aggregation, and granule secretion in response to select platelet agonists. Furthermore, a change in bioactive lipids (oxylipins) was observed in the female cohort after THC administration. These results indicate that chronic THC edible administration desensitized platelet activity and function in response to GPVI- and G-protein coupled receptor-based activation by interfering with primary and secondary feedback signaling pathways. These observations may have important clinical implications for patients who use medical marijuana and for providers caring for these patients.


Assuntos
Plaquetas/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/administração & dosagem , Dronabinol/administração & dosagem , Maconha Medicinal/administração & dosagem , Administração Oral , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Feminino , Macaca mulatta , Masculino , Oxilipinas/sangue , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Vesículas Secretórias/efeitos dos fármacos , Vesículas Secretórias/metabolismo , Transdução de Sinais , Tromboxanos/sangue , Fatores de Tempo
11.
Am J Physiol Lung Cell Mol Physiol ; 322(6): L771-L783, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35318859

RESUMO

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Influenza Humana , Lesão Pulmonar , Vaping , Acetatos/química , Animais , Humanos , Inflamação/induzido quimicamente , Lesão Pulmonar/induzido quimicamente , Macrófagos Alveolares/metabolismo , Camundongos , Estresse Oxidativo , Vaping/efeitos adversos , Vitamina E/farmacologia
12.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35055132

RESUMO

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.


Assuntos
Mucoproteínas/metabolismo , Nitrilas/administração & dosagem , Proteínas Oncogênicas/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Pirimidinas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Mucoproteínas/genética , Metástase Neoplásica , Nitrilas/farmacologia , Proteínas Oncogênicas/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Proteólise , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Drug Metab Dispos ; 49(8): 694-705, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34035125

RESUMO

3,3'-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine after oral dosing, and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse DIM 150-mg capsules (45.3 mg DIM/capsule) every evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two monohydroxylated metabolites and 1 dihydroxylated metabolite, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. Results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans, which reported only parent DIM present after oral administration. 3-((1H-indole-3-yl)methyl)indolin-2-one, identified as one of the monohydroxylated products, exhibited greater potency and efficacy as an aryl hydrocarbon receptor agonist when tested in a xenobiotic response element-luciferase reporter assay using Hepa1 cells. In addition to competitive phytochemical-drug adverse reactions, additional metabolites may exhibit pharmacological activity highlighting the importance of further characterization of DIM metabolism in humans. SIGNIFICANCE STATEMENT: 3,3'-Diindolylmethane (DIM), derived from indole-3-carbinol in cruciferous vegetables, is an effective cancer chemopreventive agent in preclinical models and a popular dietary supplement currently in clinical trials. Pharmacokinetic studies to date have found little or no metabolites of DIM in plasma or urine. In marked contrast, we demonstrate rapid appearance of mono- and dihydroxylated metabolites in human plasma and urine as well as their sulfate and glucuronide conjugates. The 3-((1H-indole-3-yl)methyl)indolin-2-one metabolite exhibited significant aryl hydrocarbon receptor agonist activity, emphasizing the need for further characterization of the pharmacological properties of DIM metabolites.


Assuntos
Indóis , Administração Oral , Anticarcinógenos/sangue , Anticarcinógenos/farmacocinética , Anticarcinógenos/urina , Cápsulas , Suplementos Nutricionais , Desenvolvimento de Medicamentos , Vias de Eliminação de Fármacos , Feminino , Humanos , Inativação Metabólica/fisiologia , Indóis/sangue , Indóis/farmacocinética , Indóis/urina , Masculino , Pessoa de Meia-Idade , Compostos Fitoquímicos/sangue , Compostos Fitoquímicos/farmacocinética , Compostos Fitoquímicos/urina
14.
Environ Res ; 197: 111069, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785325

RESUMO

This study evaluated the long-term organic removal performance and microbial community shift in simulated aquifer storage and recovery (ASR) conditions. For this purpose, anoxic soil box systems were operated at 15 °C for one year. The results showed that the assimilable organic carbon (AOC) concentration in the anoxic soil box systems was successfully decreased by 79.1%. The dissolved organic carbon (DOC) concentration increased during the initial operational periods; however, it subsequently decreased during long-term operation. Readily biodegradable organic fractions (i.e., low-molecular weight (LMW) neutrals and LMW acids) decreased along with time elapsed, whereas non-biodegradable fraction (i.e., humic substances) increased. Proteobacteria and Acidobacteriota were predominant in the anoxic box systems throughout the operational periods. Firmicutes and Bacteroidota suddenly increased during the initial operational period while Gemmatimonadota slightly increased during prolonged long-term operation. Interestingly, the microbial community structures were significantly shifted with respect to the operational periods while the effects of AOC/NO3- addition were negligible. Various bacterial species preferring low temperature or anoxic conditions were detected as predominant bacteria. Some denitrifying (i.e., Noviherbaspirillum denitrificans) and iron reducing bacteria (i.e., Geobacter spp.) appeared during the long-term operation; these bacterial communities also acted as organic degraders in the simulated ASR systems. The findings of this study suggest that the application of natural bioattenuation using indigenous soil microbial communities can be a promising option as an organic carbon management strategy in ASR systems.


Assuntos
Água Subterrânea , Microbiota , Carbono , Oxalobacteraceae , Solo
15.
Environ Res ; 191: 110033, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32810494

RESUMO

Aquifer storage and recovery (ASR) technology has been adopted as a strategic water management tool. However, during the injection of oxic and organic carbon-containing water to the underground aquifers, severe phenomena such as clogging and groundwater deterioration have been reported. To prevent these severe phenomena, assimilable organic carbon (AOC) concentration has been controlled in the ASR applications by supporting bacteria growth potential. In this study, the AOC removal strategy was investigated in a simulated ASR system using an indigenous bacterium, Pseudomonas jinjuensis. AOC removal was evaluated under three different experimental conditions: (i) 30 °C and aerobic, (ii) 15 °C and aerobic, and (iii) 15 °C and anoxic. The effects of contact media such as sand and granular activated carbon on AOC removal efficiency were also investigated. Results show that under the 30 °C aerobic condition, P. jinjuensis could remove 99.8% (13 µg L-1) of AOC with soil. The variations in the organic fractions determined by liquid chromatography with organic carbon detector analysis were observed and showed trends similar to those of AOC determined by the flow cytometry method. The indirect injection method in ASR application was recommended due to the AOC removal benefit by soil indigenous bacterium.


Assuntos
Água Subterrânea , Purificação da Água , Pseudomonas , Água
16.
Labour Econ ; 67: 101926, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989344

RESUMO

This study investigates the long-term effects of initial labor market conditions by comparing cohorts who graduated from college before, during, and after the 1997-1998 Asian financial crisis in South Korea. We measure the overall welfare effect by examining their labor market activities, family formation, and household finances. Using data from 20 waves of the Korean Labor and Income Panel Study, we find a substantial and persistent reduction in employment, earnings, marriage, fertility, and asset building among men who graduated during the recession. For women, limited job opportunities at graduation resulted in an increase in childbearing. We also find evidence that family provides a risk-sharing mechanism for recession graduates. Our results suggest that labor market entry in a large-scale recession has prolonged effects on a young worker's life course even after the penalties in the labor market have disappeared.

17.
Cell Immunol ; 340: 103905, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30827673

RESUMO

Ubiquitylation is a post-translational modification (PTM) that controls various cellular signaling pathways. It is orchestrated by a three-step enzymatic cascade know as the ubiquitin proteasome system (UPS). E3 ligases dictate the specificity to the substrates, primarily leading to proteasome-dependent degradation. Deregulation of the UPS components by various mechanisms contributes to the pathogenesis of cancer. This review focuses on E3 ligase-substrates pairings that are implicated in B-cell malignancies. Understanding the molecular mechanism of specific E3 ubiquitin ligases will present potential opportunities for the development of targeted therapeutic approaches.


Assuntos
Leucemia de Células B/imunologia , Complexo de Endopeptidases do Proteassoma/imunologia , Processamento de Proteína Pós-Traducional , Ubiquitina-Proteína Ligases/genética , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Bortezomib/uso terapêutico , Humanos , Isoenzimas/genética , Isoenzimas/imunologia , Leucemia de Células B/tratamento farmacológico , Leucemia de Células B/genética , Leucemia de Células B/patologia , Terapia de Alvo Molecular/métodos , NF-kappa B/genética , NF-kappa B/imunologia , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/imunologia , Ubiquitinação
18.
Opt Express ; 26(24): 31567-31576, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30650740

RESUMO

Mass sensing offering both a broad detection range and a high resolving power is essential for quantitative precision content analysis and high-yield mass production of various kinds of materials. Here, we propose and successfully demonstrate a novel type of simple low-cost optomechanical mass sensing employing an optical displacement detector that consists of a free-space Fabry-Pérot optical cavity and an intra-cavity wedge prism pair, which provides an enhanced resolution and an extended capacity simultaneously. By implementing the null-method-based scheme of mass measurement, we achieve a resolution higher than 5000:1 (mass range from <200 mg to >1 kg) and an excellent linearity of R2>0.99998 in the prototype demonstration.

19.
Mol Cell Biochem ; 442(1-2): 187-201, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28993959

RESUMO

It is commonly accepted that brain phospholipids are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC-MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs.


Assuntos
Encéfalo/metabolismo , Ácidos Graxos Insaturados/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Fosfolipídeos/metabolismo , Animais , Masculino , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley
20.
BMC Psychiatry ; 17(1): 274, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754158

RESUMO

BACKGROUND: Previous studies have examined associations between sitting time and negative health outcomes and mental health. However, the relationship between overall sitting time and major depressive disorder (MDD) in South Korea has not been studied. This study examined the association between MDD and overall sitting time and physical activity in South Koreans. METHODS: Data from the sixth Korean National Health and Nutrition Examination Survey (KNHANES), a cross-sectional, nationally representative survey, were analyzed. Total participants were 4145 in 2014. MDD was assessed using the Patient Health Questionnaire (PHQ-9). Participants' data regarding self-reported sitting time and physical activity were analyzed via multiple logistic regression. RESULTS: Results showed that people who sat for 8-10 h (OR: 1.56, 95% CI: 1.15-2.11) or more than 10 h (OR: 1.71, 95% CI: 1.23-2.39) had increased risk of MDD compared to those who sat for less than 5 h a day. Subgroup analysis showed that the strongest effect of reported sitting time on risk of MDD was found in men with lower levels of physical activity who sat for 8 to 10 h (OR: 3.04, 95% CI: 1.15-8.01) or more than 10 h (OR: 3.43, 95% CI: 1.26-9.35). Level of physical activity was not an independent predictor for MDD. CONCLUSIONS: Sitting for long periods was associated with greater risk of MDD in South Korean adults. Reducing sitting time in people with MDD could help to prevent associated physical health problems and may improve mental health.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Exercício Físico/psicologia , Postura , Fatores de Tempo , Adulto , Estudos Transversais , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia , Comportamento Sedentário , Autorrelato
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