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1.
Adv Mater ; : e2312451, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688700

RESUMO

Li-ion batteries are essential technologies for electronic products in the daily life. However, serious fire safety concerns that are closely associated with the flammable liquid electrolyte remains a key challenge. Tremendous effort has been devoted to designing nonflammable liquid electrolytes. It is critical to gain comprehensive insights into nonflammability design and inspire more efficient approaches for building safer Li-ion batteries. This review presents current mechanistic understanding of safety issues and discusses state-of-the-art nonflammable liquid electrolytes design for Li-ion batteries based on molecule, solvation, and battery compatibility level. Various safety test methods are discussed for reliable safety risk evaluation. Finally, the challenges and perspectives of the nonflammability design for Li-ion electrolytes are summarized.

2.
ACS Nano ; 18(16): 10726-10737, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38602344

RESUMO

Ether-based high-voltage lithium metal batteries (HV-LMBs) are drawing growing interest due to their high compatibility with the Li metal anode. However, the commercialization of ether-based HV-LMBs still faces many challenges, including short cycle life, limited safety, and complex failure mechanisms. In this Review, we discuss recent progress achieved in ether-based electrolytes for HV-LMBs and propose a systematic design principle for the electrolyte based on three important parameters: electrochemical performance, safety, and industrial scalability. Finally, we summarize the challenges for the commercial application of ether-based HV-LMBs and suggest a roadmap for future development.

3.
J Biol Chem ; 300(3): 105759, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367666

RESUMO

Genome-wide association studies have reported a correlation between a SNP of the RING finger E3 ubiquitin protein ligase rififylin (RFFL) and QT interval variability in humans (Newton-Cheh et al., 2009). Previously, we have shown that RFFL downregulates expression and function of the human-like ether-a-go-go-related gene potassium channel and corresponding rapidly activating delayed rectifier potassium current (IKr) in adult rabbit ventricular cardiomyocytes. Here, we report that RFFL also affects the transient outward current (Ito), but in a peculiar way. RFFL overexpression in adult rabbit ventricular cardiomyocytes significantly decreases the contribution of its fast component (Ito,f) from 35% to 21% and increases the contribution of its slow component (Ito,s) from 65% to 79%. Since Ito,f in rabbits is mainly conducted by Kv4.3, we investigated the effect of RFFL on Kv4.3 expressed in HEK293A cells. We found that RFFL overexpression reduced Kv4.3 expression and corresponding Ito,f in a RING domain-dependent manner in the presence or absence of its accessory subunit Kv channel-interacting protein 2. On the other hand, RFFL overexpression in Kv1.4-expressing HEK cells leads to an increase in both Kv1.4 expression level and Ito,s, similarly in a RING domain-dependent manner. Our physiologically detailed rabbit ventricular myocyte computational model shows that these yin and yang effects of RFFL overexpression on Ito,f, and Ito,s affect phase 1 of the action potential waveform and slightly decrease its duration in addition to suppressing IKr. Thus, RFFL modifies cardiac repolarization reserve via ubiquitination of multiple proteins that differently affect various potassium channels and cardiac action potential duration.


Assuntos
Miócitos Cardíacos , Canais de Potássio Shal , Ubiquitina-Proteína Ligases , Animais , Humanos , Coelhos , Potenciais de Ação/fisiologia , Estudo de Associação Genômica Ampla , Miócitos Cardíacos/metabolismo , Potássio/metabolismo , Canais de Potássio Shal/genética , Canais de Potássio Shal/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Células HEK293
4.
J Hazard Mater ; 463: 132822, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-37898090

RESUMO

Organic ultraviolet filters (OUVFs) have been used globally for the past 20 years. Given that OUVFs can be quickly released from sunscreens applied on human skins, they have been frequently detected in aquatic environments and organisms. Some byproducts of OUVFs might be more recalcitrant and toxic than their parent compounds. To further assess the toxicity and potential risk of OUVFs' byproducts, it is necessary to determine the fate of OUVFs and identify their transformation products. This review summarizes and analyzes pertinent literature and reports in the field of OUVFs research. These published research works majorly focus on the degradation mechanisms of OUVFs in aquatic environments, their intermediates/byproducts, and chlorination reaction. Photodegradation (direct photolysis, self-sensitive photolysis and indirect photolysis) and biodegradation are the main transformation pathways of OUVFs through natural degradation. To remove residual OUVFs' pollutants from aqueous environments, novel physicochemical and biological approaches have been developed in recent years. Advanced oxidation, ultrasound, and bio-based technologies have been proven to eliminate OUVFs from wastewaters. In addition, the disinfection mechanism and the byproducts (DBPs) of various OUVFs in swimming pools are discussed in this review. Besides, knowledge gaps and future research directions in this field of study are also mentioned.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Humanos , Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Raios Ultravioleta , Protetores Solares/toxicidade , Desinfecção , Fotólise
5.
Environ Sci Technol ; 57(44): 17110-17122, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37851929

RESUMO

Organic ultraviolet filters (OUVFs) are extensively released into aquatic environments, where they undergo complex phototransformation. However, there is little knowledge regarding their transformation products (TPs) and associated endocrine disruption potentials. In the present study, we characterized the chemical and toxicological profiles of TPs for two common OUVFs, oxybenzone (BP3) and ethylhexyl methoxycinnamate (EHMC), by photooxidation under environmentally relevant conditions. It is hypothesized that TPs of the tested OUVFs will show varied estrogenicity at different reaction times. High-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) identified 17 TPs of 7 m/z for BP-3 and 13 TPs of 8 m/z for EHMC at confidence levels ≤2. Five novel TPs of 2 m/z were reported for the first time with structure-diagnostic MS/MS spectra. Estrogenicity assessment using the MCF-7-luc cell line showed discrepant estrogenic activities exhibited by OUVF-TPs over time. Specifically, BP3-TPs exhibited significantly greater estrogenicity than the parent at several reaction times, whereas EHMC-TPs displayed fluctuating estrogenicity with a declining trend. Correlation analysis coupled with molecular docking simulations further suggested several TPs of BP3 as potential endocrine disruptive compounds. These findings underscore the necessity of considering mixtures during chemical testing and risk assessment and highlight the potentially greater risks associated with post-transformation cocktails.


Assuntos
Espectrometria de Massas em Tandem , Poluentes Químicos da Água , Espectrometria de Massas em Tandem/métodos , Raios Ultravioleta , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/análise
6.
Environ Int ; 180: 108212, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37738697

RESUMO

Indoor dust contaminated with liquid crystal monomers (LCMs) released from various commercial liquid crystal display (LCD) screens may pose environmental health risks to humans. This study aimed to investigate the occurrence of 64 LCMs in ventilation and air conditioning filters (VACF) dust, characterize their composition profiles, potential sources, and associations with indoor characteristics, and assess their in vitro toxicity using the human lung bronchial epithelial cells (BEAS-2B). A total of 31 LCMs with concentrations (ΣLCMs) ranging from 43.7 ng/g to 448 ng/g were detected in the collected VACF dust. Additional analysis revealed the potential interactions between indoor environmental conditions and human exposure risks associated with the detected LCMs in VACF dust. The service area and working time of the ventilation and air conditioning system, and the number of indoor LCD screens were positively correlated with the fluorinated ΣLCMs in VACF dust (r = 0.355 âˆ¼ 0.511, p < 0.05), while the associations with the non-fluorinated ΣLCMs were not found (p > 0.05), suggesting different environmental behavior and fates of fluorinated and non-fluorinated LCMs in the indoor environment. Four main indoor sources of LCMs (i.e., computer (37.1%), television (28.3%), Brand A smartphone (21.2%) and Brand S smartphone (13.4%)) were identified by positive matrix factorization-multiple linear regression (PMF-MLR). Exposure to 14 relatively frequently detected LCMs, individually and in the mixture, induced significant oxidative stress in BEAS-2B cells. Among them, non-fluorinated LCMs, specifically 3cH2B and MeP3bcH, caused dominant decreased cell viability. This study provides new insights into the indoor LCMs pollution and the associated potential health risks due to the daily use of electronic devices.

7.
Cell Death Dis ; 14(6): 352, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291088

RESUMO

Idiopathic pulmonary fibrosis is a progressive fibrotic disorder with no cure that is characterized by deterioration of lung function. Current FDA-approved drugs for IPF delay the decline in lung function, but neither reverse fibrosis nor significantly improve overall survival. SHP-1 deficiency results in hyperactive alveolar macrophages accumulating in the lung, which contribute to the induction of pulmonary fibrosis. Herein, we investigated whether employing a SHP-1 agonist ameliorates pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis murine model. Histological examination and micro-computed tomography images showed that SHP-1 agonist treatment alleviates bleomycin-induced pulmonary fibrosis. Reduced alveolar hemorrhage, lung inflammation, and collagen deposition, as well as enhanced alveolar space, lung capacity, and improved overall survival were observed in mice administered the SHP-1 agonist. The percentage of macrophages collected from bronchoalveolar lavage fluid and circulating monocytes in bleomycin-instilled mice were also significantly reduced by SHP-1 agonist treatment, suggesting that the SHP-1 agonist may alleviate pulmonary fibrosis by targeting macrophages and reshaping the immunofibrotic niche. In human monocyte-derived macrophages, SHP-1 agonist treatment downregulated CSF1R expression and inactivated STAT3/NFκB signaling, culminating in inhibited macrophage survival and perturbed macrophage polarization. The expression of pro-fibrotic markers (e.g., MRC1, CD200R1, and FN1) by IL4/IL13-induced M2 macrophages that rely on CSF1R signaling for their fate-determination was restricted by SHP-1 agonist treatment. While M2-derived medium promoted the expression of fibroblast-to-myofibroblast transition markers (e.g., ACTA2 and COL3A1), the application of SHP-1 agonist reversed the transition in a dose-dependent manner. Our report indicates that pharmacological activation of SHP-1 ameliorates pulmonary fibrosis via suppression of CSF1R signaling in macrophages, reduction of pathogenic macrophages, and the inhibition of fibroblast-to-myofibroblast transition. Our study thus identifies SHP-1 as a druggable target for the treatment of IPF, and suggests that the SHP-1 agonist may be developed as an anti-pulmonary fibrosis medication that both suppresses inflammation and restrains fibroblast-to-myofibroblast transition.


Assuntos
Fibrose Pulmonar Idiopática , Macrófagos , Camundongos , Humanos , Animais , Microtomografia por Raio-X , Macrófagos/metabolismo , Pulmão/metabolismo , Inflamação/patologia , Fibrose Pulmonar Idiopática/patologia , Bleomicina/uso terapêutico , Fibrose , Camundongos Endogâmicos C57BL
8.
Elife ; 122023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37204302

RESUMO

Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. Senescent cells interfere with cardiac function and outcome post-MI with age, but studies have not been performed in larger animals, and the mechanisms are unknown. Specifically, age-associated changes in timecourse of senescence and related changes in inflammation and fibrosis are not well understood. Additionally, the cellular and systemic role of senescence and its inflammatory milieu in influencing arrhythmogenesis with age is not clear, particularly in large animal models with cardiac electrophysiology more similar to humans than previously studied animal models. Here, we investigated the role of senescence in regulating inflammation, fibrosis, and arrhythmogenesis in young and aged infarcted rabbits. Aged rabbits exhibited increased peri-procedural mortality and arrhythmogenic electrophysiological remodeling at the infarct border zone (IBZ) compared to young rabbits. Studies of the aged infarct zone revealed persistent myofibroblast senescence and increased inflammatory signaling over a 12-week timecourse. Senescent IBZ myofibroblasts in aged rabbits appear to be coupled to myocytes, and our computational modeling showed that senescent myofibroblast-cardiomyocyte coupling prolongs action potential duration (APD) and facilitates conduction block permissive of arrhythmias. Aged infarcted human ventricles show levels of senescence consistent with aged rabbits, and senescent myofibroblasts also couple to IBZ myocytes. Our findings suggest that therapeutic interventions targeting senescent cells may mitigate arrhythmias post-MI with age.


Assuntos
Infarto do Miocárdio , Miofibroblastos , Animais , Coelhos , Humanos , Idoso , Miofibroblastos/patologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Arritmias Cardíacas , Fibrose , Inflamação/patologia
9.
ChemSusChem ; 16(16): e202300361, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37139577

RESUMO

Carbon nitride (CN) polymers exhibit tunable and fascinating physicochemical properties and are thus an essential class of photocatalytic materials with potential applications. Although significant progress has been made in the fabrication of CN, the preparation of metal-free crystalline CN via a straightforward method remains a considerable challenge. Herein, we describe a new attempt to synthesize crystalline carbon nitride (CCN) with a well-developed structure through regulation of the polymerization kinetics. The synthetic process involves the pre-polymerization of melamine to remove most of the ammonia and further calcination of the pre-heated melamine in the presence of copper oxide as an ammonia absorbent. Copper oxide can decompose the ammonia produced by the polymerization process, thereby promoting the reaction. These conditions facilitate the polycondensation process while avoiding carbonization of the polymeric backbone at high temperatures. Owing to the high crystallinity, nanosheet structure, and efficient charge-carrier transmission capacity, the as-prepared CCN catalyst shows much higher photocatalytic activity than its counterparts. Our study provides a novel strategy for the rational design and synthesis of high-performance carbon nitride photocatalysts by simultaneously optimizing polymerization kinetics and crystallographic structures.

10.
J Acoust Soc Am ; 153(2): 972, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36859134

RESUMO

Environmental noise has long been considered one of the unwelcome aspects of urban life at home. An increasing number of scholars have studied improving indoor acoustic comfort by using the soundscape approach. However, much uncertainty still exists about the relationship between the audio-visual environment and indoor soundscape perception. The current study investigates the interaction effects of traffic sound and window views on indoor soundscape perceptions in residential contexts. Thirty-two participants were presented with 51 scenarios (a combination of 17 window views and three aural stimuli) and requested to assess their soundscape perceptions in a VR experiment. Results showed that traffic noise could moderate the impact of nature, road, and building views on pleasantness, while it can also moderate the effect of water sound and road view on eventfulness. In particular, natural window views were found not to lead to a more pleasant indoor soundscape necessarily; natural window views even decrease the pleasantness of indoor soundscape in the case of heavy traffic noise outside the window. Besides, overall visual indicators, including complexity and openness, have an interactive effect with traffic sound on pleasantness. Last, pleasantness is found to be associated with the appropriateness of indoor soundscape.


Assuntos
Acústica , Som , Humanos , Emoções , Incerteza , Água
12.
Science ; 379(6631): 436-437, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36730403

RESUMO

A solid-state electrolyte enables a lithium-air battery to operate at 25°C.

13.
Nanomicro Lett ; 14(1): 222, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36374367

RESUMO

Lithium-sulfur (Li-S) batteries are promising candidates for next-generation energy storage systems owing to their high energy density and low cost. However, critical challenges including severe shuttling of lithium polysulfides (LiPSs) and sluggish redox kinetics limit the practical application of Li-S batteries. Carbon nitrides (CxNy), represented by graphitic carbon nitride (g-C3N4), provide new opportunities for overcoming these challenges. With a graphene-like structure and high pyridinic-N content, g-C3N4 can effectively immobilize LiPSs and enhance the redox kinetics of S species. In addition, its structure and properties including electronic conductivity and catalytic activity can be regulated by simple methods that facilitate its application in Li-S batteries. Here, the recent progress of applying CxNy-based materials including the optimized g-C3N4, g-C3N4-based composites, and other novel CxNy materials is systematically reviewed in Li-S batteries, with a focus on the structure-activity relationship. The limitations of existing CxNy-based materials are identified, and the perspectives on the rational design of advanced CxNy-based materials are provided for high-performance Li-S batteries.

14.
Comput Intell Neurosci ; 2022: 4952215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045986

RESUMO

It is hard to forecasting oil future prices accurately, which is affected by some nonlinear, nonstationary, and other chaotic characteristics. Then, a novel GA-SVR-GRNN hybrid deep learning algorithm is put forward for forecasting oil future price. First, a genetic algorithm (GA) is employed for optimizing parameters regarding the support vector regression machine (SVR), and the GA-SVR model is used to forecast oil future price. Further, a generalized regression neural network (GRNN) model is built for the residual series for forecasting. Finally, we obtain the predicted values of the oil future price series forecasted by the GA-SVR-GRNN hybrid deep learning algorithm. According to the simulation, the GA-SVR-GRNN hybrid deep learning algorithm achieves lower MSE, RMSE, MAE, and MAPE relative to the GRNN, GA-SVR, and PSO-SVR models, indicating that the proposed GA-SVR-GRNN hybrid deep learning algorithm can fully reveal the prediction advantages of the GA-SVR and GRNN models in the nonlinear space and is a more accurate and effective method for oil future price forecasting.


Assuntos
Aprendizado Profundo , Simulação por Computador , Previsões , Redes Neurais de Computação , Máquina de Vetores de Suporte
15.
J Environ Public Health ; 2022: 3741370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795536

RESUMO

Accurate prediction of crude oil prices (COPs) is a challenge for academia and industry. Therefore, the present research developed a new CEEMDAN-GA-SVR hybrid model to predict COPs, incorporating complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), a genetic algorithm (GA), and support vector regression machine (SVR). First, our team utilized CEEMDAN to realize the decomposition of a raw series of COPs into a group of comparatively simpler subseries. Second, SVR was utilized to predict values for every decomposed subseries separately. Owing to the intricate parametric settings of SVR, GA was employed to achieve the parametric optimisation of SVR during forecast. Then, our team assembled the forecasted values of the entire subseries as the forecasted values of the CEEMDAN-GA-SVR model. After a series of experiments and comparison of the results, we discovered that the CEEMDAN-GA-SVR model remarkably outperformed single and ensemble benchmark models, as displayed by a case study finished based on a time series of weekly Brent COPs.


Assuntos
Petróleo , Máquina de Vetores de Suporte , Previsões
16.
J Hazard Mater ; 430: 128499, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35739679

RESUMO

The partitioning between phospholipids/proteins and water can be used to predict the bioaccumulation potential of chemicals with better accuracy compared with n-octanol-water partition coefficient. However, such partitioning is poorly understood for chiral chemicals, many of which exhibit differential bioaccumulation and toxicity potential between enantiomers. In this study, the enantiospecific liposome-water and bovine serum albumin (BSA)-water partition coefficients (Klip/w and KBSA/w, determined at 25 ℃ and 37 ℃, respectively) were measured by equilibrium dialysis for α-, ß-, and γ-hexabromocyclododecane (HBCD) and three ß-blockers (propranolol, metoprolol, and sotalol). Raman and fluorescence analyses and molecular docking were conducted to provide additional insights into the partitioning process. Results showed α- and ß-HBCD displayed stronger enantioselective partitioning to liposomes with the (-)-form, while (-)-α-HBCD, R-(+)-propranolol, R-(+)-metoprolol, and E2-sotalol favored partitioning to BSA compared with their antipodes. Raman spectra revealed α- and γ-HBCD enhanced and reduced the organization of liposome acyl chains, respectively, and polar interactions enhanced the liposome partitioning of ß-blockers. Fluorescence spectra indicated the changed tryptophan microenvironment might influence the BSA steric effect toward HBCD, and electrostatic interactions dominated the formation of BSA-ß-blocker complexes. Molecular docking results supported the difference in the thermodynamic nature of interaction between the studied enantiomers and BSA.


Assuntos
Lipossomos , Água , Lipossomos/química , Metoprolol , Simulação de Acoplamento Molecular , Fosfolipídeos , Propranolol , Soroalbumina Bovina/química , Sotalol , Água/química
17.
J Environ Sci (China) ; 117: 10-20, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35725062

RESUMO

2,6-Dichloro-1,4-benzoquinone (2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization (dpf). Following exposure to 2,6-DCBQ (20 and 100 µg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17ß-estradiol (E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes (cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver (HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17ß-estradiol level.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Benzoquinonas , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Moduladores de Receptor Estrogênico/metabolismo , Feminino , Masculino , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
18.
Small ; 18(43): e2200009, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35315571

RESUMO

The rechargeable magnesium battery (RMB) is regarded as a high-energy, safe, and cost-effective alternative for conventional batteries. Unfortunately, the passivation and uneven Mg growth not only raise the voltage hysteresis but also shorten the cycle life of RMBs. In this review, Mg passivation induced by electrolytes/contaminants, growth patterns of high dimensional Mg0 , and mechanisms of Mg anode degradation are discussed. The recent efforts on suppressing electrolyte decomposition and uneven Mg growth including electrolyte/interphase modifications through additives, weakly coordinating anions, artificial interphases, and 3D magnesiophilic hosts are summarized. Finally, the future directions in stabilizing Mg anode and realizing high-performance RMBs are highlighted.


Assuntos
Eletrólitos , Magnésio , Eletrodos , Interfase
19.
Oncogene ; 41(13): 1907-1917, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35149839

RESUMO

CBL family proteins (CBL, CBLB and CBLC in mammals) are E3 ubiquitin ligases of protein tyrosine kinases. CBL mediates the lysosomal degradation of activated EGFR through K63-linked ubiquitination, while CBLC has an oncogenic function by positively regulating EGFR activation through K6 and K11-linked ubiquitination in EGFR mutant lung adenocarcinoma (LAD). Here, we used immunoprecipitation and mass spectrometry to study the CBLC interactome, and found that CBLC is also involved in cell cycle regulation by stabilizing Aurora kinase A (AURKA). CBLC interacted with the kinase domain of AURKA and positively regulated the stability of AURKA by conjugating monoubiquitination and K11/K63-linked polyubiquitination, which are protective from degrading K11/K48 polyubiquitination. CBLC depletion markedly decreased the half-life of AURKA in cycloheximide-treated LAD cells. When LAD cells were synchronized with double thymidine block at the G1/S boundary and then released into mitotic arrest, CBLC depletion delayed the accumulation and activation of AURKA and prevented cancer cells from entering mitosis. CBLC deficiency significantly delayed cell cycle progression, reduced the mitotic population, and increased apoptosis of LAD cells. Targeting CBLC inhibited tumor growth of LAD cells and enhanced their sensitivity to paclitaxel in xenograft models. Immunohistochemical staining of the tissue microarray also revealed a positive correlation between the expression of CBLC and AURKA in normal and LAD tissues, further supporting the positive regulation of AURKA expression by CBLC. In summary, these findings indicate that the oncogenic E3 ligase CBLC plays a role in mitotic entry by stabilizing AURKA via ubiquitination in LAD. This work demonstrates that targeting CBLC combined with paclitaxel might be a potential option for the treatment of LAD patients who have no available targeted therapies.


Assuntos
Adenocarcinoma de Pulmão , Aurora Quinase A , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-cbl , Adenocarcinoma de Pulmão/genética , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Linhagem Celular Tumoral , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Paclitaxel , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Ubiquitinação
20.
J Hazard Mater ; 423(Pt B): 127146, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536849

RESUMO

Liquid crystal monomers (LCMs) have been proposed as a class of emerging organic pollutants, which were recently detected in indoor dust and sediment samples collected near electronic devices recycling facilities. However, there is a knowledge gap for analytical method, occurrence, and distribution of LCMs in aqueous sample. Herein, a robust method was developed to determine 38 target LCMs in landfill leachate. A combined ultrasonic enhanced liquid-liquid extraction, saponification and silica/florisil packed column purification method achieved recoveries of 76.9~127.1%, 84.5~114.6% and 81.3~104.6% at spiking levels of 2 ng, 10 ng and 50 ng in leachate, respectively. The developed method was validated through determination of target LCMs in leachate samples collected from municipal landfills in Hong Kong (HK) and Shenzhen (SZ), China. There were 23 and 20 LCMs detected in the HK (ΣLCMs=1120 ng/L) and SZ (ΣLCMs=409 ng/L) sample, respectively, with 6 LCMs newly detected in the environment. This study provided the first evidence suggesting that landfill leachate might be a potential sink of LCMs emitted from e-waste. Future study is urged to investigate the potential migration of LCMs from landfill leachate as a point source, and their occurrence, distribution, fate, and ecotoxicological risk in aquatic environments on regional and global scales.


Assuntos
Resíduo Eletrônico , Poluentes Ambientais , Cristais Líquidos , Eliminação de Resíduos , Poluentes Químicos da Água , Resíduos Sólidos/análise , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/análise
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