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1.
Entropy (Basel) ; 26(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38667882

RESUMO

Automatic crack segmentation plays an essential role in maintaining the structural health of buildings and infrastructure. Despite the success in fully supervised crack segmentation, the costly pixel-level annotation restricts its application, leading to increased exploration in weakly supervised crack segmentation (WSCS). However, WSCS methods inevitably bring in noisy pseudo-labels, which results in large fluctuations. To address this problem, we propose a novel confidence-aware co-training (CAC) framework for WSCS. This framework aims to iteratively refine pseudo-labels, facilitating the learning of a more robust segmentation model. Specifically, a co-training mechanism is designed and constructs two collaborative networks to learn uncertain crack pixels, from easy to hard. Moreover, the dynamic division strategy is designed to divide the pseudo-labels based on the crack confidence score. Among them, the high-confidence pseudo-labels are utilized to optimize the initialization parameters for the collaborative network, while low-confidence pseudo-labels enrich the diversity of crack samples. Extensive experiments conducted on the Crack500, DeepCrack, and CFD datasets demonstrate that the proposed CAC significantly outperforms other WSCS methods.

2.
J Environ Manage ; 357: 120777, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581893

RESUMO

Accurate quantification of dissolved oxygen (DO) is critically important for the protection and management of aquatic ecosystems. Successful applications have utilized mechanistic and data-driven models to simulate DO content in aquatic ecosystems. However, mechanistic models present challenges due to their complex and difficult-to-solve conditions, making them less portable. Additionally, data-driven model predictions are hindered by the challenge of numerous input variables, impacting both the running speed and prediction performance of the model. To address these challenges, water quality data and meteorological data of the Tanjiang River were obtained. The maximum information coefficient (MIC) input variable selection technique was employed to identify primary environmental factors influencing DO changes. Furthermore, coupled with support vector regression (SVR), two models (SVR and MIC-SVR) were employed to estimate the DO concentration of the Tanjiang River, and the optimal model was established. The results indicated a shift in the primary pollution factor from ammonia nitrogen to total phosphorus after recent treatment in the Tanjiang River. In comparison with the SVR model, the root mean square error (RMSE) of the MIC-SVR model was reduced by 4.46%, and the Nash-efficiency coefficient (NSE) was improved by 45.85%. In addition, study of kernel function selection revealed that considering as many kernel functions as possible is necessary for improving the performance of the SVR model. Conclusively, the proposed MIC-SVR model serves as an effective tool to analyze the relationship between DO and environmental factors, identifying the primary causes of low DO, and accurately predict the DO concentration in the Tanjiang River (especially in its middle and lower reaches), thus providing a reference for governmental decision-making on water environmental protection and water resource management.


Assuntos
Monitoramento Ambiental , Oxigênio , Monitoramento Ambiental/métodos , Ecossistema , Algoritmos , Aprendizado de Máquina , Rios
3.
Fitoterapia ; 175: 105948, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588904

RESUMO

Four new undescribed halimane- and labdane-type diterpenoids, named zeylleucapenoids E-H (1-4), along with four known analogues (5-8), were isolated from the aerial parts of Leucas zeylanica (L.) R. Br. Their structures were determined by comprehensive spectroscopic analysis and computational calculations. Compounds 1 and 2 are the highly modified halimane diterpenoids featuring a 6/6/6-fused tricyclic system with an unusual six-membered 6,11-ether ring. Compound 8 exhibits nontoxic effects for zebrafish embryo, while it displays efficient reduction against NO production in a dose-dependent manner and strongly suppresses the secretion of LPS-induced TNF-α and IL-6 cytokines in RAW264.7 macrophages. In addition, marked reductions of iNOS and COX-2 expression were observed. Molecular docking analysis indicated that 8 has high affinities with the target amino acid residues on protein-binding sites, which may be a possible mechanism contributing to the anti-inflammatory potential of this molecule.

4.
Nat Commun ; 15(1): 2777, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555416

RESUMO

Garnet-type Li6.5La3Zr1.5Ta0.5O12 (LLZO) is considered a promising solid electrolyte, but the surface degradation in air hinders its application for all-solid-state battery. Recent studies have mainly focused on the final products of the LLZO surface reactions due to lacking of powerful in situ characterization methods. Here, we use ambient pressure X-ray spectroscopies to in situ investigate the dynamical evolution of LLZO surface in different gas environments. The newly developed ambient pressure mapping of resonant Auger spectroscopy clearly distinguishes the lithium containing species, including LiOH, Li2O, Li2CO3 and lattice oxygen. The reaction of CO2 with LLZO to form Li2CO3 is found to be a thermodynamically favored self-limiting reaction. On the contrary, the reaction of H2O with LLZO lags behind that of CO2, but intensifies at high pressure. More interestingly, the results provide direct spectroscopic evidence for the existence of Li+/H+ exchange and reveal the importance of the initial layer formed on clean electrolyte surface in determining their air stability. This work demonstrates that the newly developed in situ technologies pave a new way to investigate the oxygen evolution and surface degradation mechanism in energy materials.

5.
J Adolesc ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506257

RESUMO

BACKGROUND: It has been demonstrated that self-efficacy and coping styles are related. However, whether there is a reciprocal longitudinal relation between self-efficacy and coping styles needs to be examined. In this longitudinal study, we tested the reciprocal impacts of self-efficacy and coping styles, taking into account the role of future self-continuity (FSC) in these effects. METHODS: The sample included 346 university students in central and southwestern China (48.3% female; Mage = 21.20). Three waves of questionnaire data were collected at half-year intervals. Cross-lagged models were adopted for data analysis. RESULTS: Self-efficacy at Waves 1 and 2 positively predicted positive coping style at Waves 2 and 3, and positive coping style at Waves 1 and 2 positively predicted self-efficacy at Waves 2 and 3. Self-efficacy at Waves 1 and 2 negatively predicted negative coping style at Waves 2 and 3, while negative coping style at Waves 1 and 2 did not significantly predict self-efficacy at Waves 2 and 3. These results indicated the reciprocal causation of self-efficacy and coping styles. Additionally, the mediation analysis revealed that FSC at Wave 2 played a mediating role in the unidirectional association between self-efficacy at Wave 1 and negative coping style at Wave 3. CONCLUSIONS: These findings suggest that self-efficacy and coping style have mutual influences over time partly explained by university students' FSC. Consequently, the results offer potential applied value for promoting positive coping strategies among university students.

6.
Psych J ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38298176

RESUMO

The existing scales for measuring balanced time perspective (BTP) have limitations, such as poor-fitting structures or a complex calculation method. Based on previous studies, we conceptualize BTP as an individual's overall positive outlook on the past and future and mindfully living in the present. The present study aimed to develop the Time Perspective Inventory (TPI) for Chinese adults, determine its psychometric properties, and examine a simple calculation method for generating a score to represent BTP. In study 1, a 7-factor structure of TPI - Past Positive, Past Negative, Mindful Present, Present Hedonistic, Present Excessively Task-oriented, Future Positive, and Future Negative - was established through exploratory (sample 1, N = 529) and confirmatory (sample 2, N = 577) factor analyses. Findings supported the internal consistency, test-retest reliability, and criterion-related validity of the TPI. We proposed using the score difference between positive time perspectives and negative time perspectives to calculate the BTP. Findings showed that the correlations between BTP and subjective well-being indicators and anxiety were higher than among individual dimensions of TPI. Study 2 (sample 3, N = 713) compared the effects of the TPI and the Chinese version of the Zimbardo Time Perspective Inventory (ZTPI-C) on well-being indicators and anxiety. Results indicated that the variance of life satisfaction, positive affect, negative affect, and anxiety explained by BTP measured with TPI was higher than deviation from BTP (DBTP) measured with ZTPI-C. Together, the TPI yields reliable and valid BTP scores among Chinese adults.

7.
J Psychol ; : 1-21, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181206

RESUMO

The purpose of this research is to investigate the prediction effect of future self-continuity (FSC) on health-promoting behaviors (Health Responsibility, Physical Activity, and Nutritional Habits) and the impact of urban-rural differences in Chinese college students, further verifying the effect of mental imagery practice on enhancing FSC and promoting health-promoting behaviors among students from rural areas. Study 1 used the Future Self-Continuity Questionnaire and a sub-scale of the Health Promotion Lifestyle Profile-II to examine the relationship between FSC and health-promoting behaviors among 788 college students (430 from rural areas and others from urban areas). Study 2 was designed to examine the impact of intervention on FSC and health-promoting behaviors among Chinese rural students. The intervention activities lasting 4 wk. 162 freshmen were randomly divided into intervention or control groups to practice the mental imagery about the future self or meditation in the present once a week. FSC and health-promoting behaviors were tested for 3 times. The results demonstrated that: (1) Rural students had lower scores in FSC and health-promoting behaviors than urban students; (2) Urban-rural differences of students moderated the effect of FSC on health-promoting behaviors; (3) The mental imagery practiced increased FSC; and (4) FSC played a complete mediating role in the effect of condition (intervention or not) on health-promoting behaviors for rural college students. Overall, these findings contribute to a deeper understanding of the relationship between FSC and health-promoting behaviors, and suggest that mental imagery practice can increase Chinese rural college students' health-promoting behaviors by enhancing their FSC.

8.
Phys Chem Chem Phys ; 26(2): 1030-1038, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38093680

RESUMO

Layered MoSSe nanostructures have been shown as potential candidates for the anode of lithium ion (Li-ion) batteries. The diffusion properties are generally critical to the performance of ionic batteries. The possible migration paths and associated diffusion energy barriers of Li-ions are systematically explored in MoSSe bilayer anodes with different stacking patterns by means of first-principles simulations. It is found that the diffusion properties strongly depend on interfaces and stacking patterns. Furthermore, the simulation results show that the diffusion energy barrier (and thus the diffusion coefficient) can be significantly reduced (enlarged) by applying a positive strain gradient, while increased (reduced) by applying a negative one. For example, the diffusion coefficient is increased roughly by 100 times relative to that of the pristine one when subjected to a strain gradient of 0.02 Å-1. In particular, it is found that less maximum strain is required in the strain-gradient than the uniform strain in order to achieve the same diffusion energy barrier. By careful analysis, the underlying mechanism can be attributed to the flexo-diffusion coupling effect. The coupling strength is characterized by the so-called flexo-diffusion coupling constant which is also calculated for each simulation model. The results of this work may provide valuable insights into the design and optimization of the anodes of ionic batteries.

9.
Antimicrob Resist Infect Control ; 12(1): 71, 2023 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-37455322

RESUMO

BACKGROUND: Disinfectant towelettes are increasingly being used as a means to prevent transmission of clinically important pathogens which could lead to healthcare-associated infections (HAIs). However, the efficacy of disinfectant towelette products when tested under realistic use conditions is understudied. A test model was designed to replicate realistic wiping conditions. The objective of this study was to determine the impact of varied contact time on disinfectant towelette efficacy under these conditions. METHODS: Five product types were tested against Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 15,442) at five contact times (30 s, one min, two min, three min, and 10 min) on hard, non-porous laminate templates to determine the impact of contact time on disinfectant towelette efficacy when tested under realistic use. RESULTS: Product type had a significant impact on the efficacy of disinfectant towelettes when tested under conditions reflective of realistic use. The effect of contact time was limited and no differences in efficacy were seen at a contact time of one min compared with the other contact times tested. Only one disinfectant towelette product achieved a mean 5-log reduction under the tested conditions. CONCLUSION: Efficacy of disinfectant towelettes was primarily impacted by product type when applied in a model designed to replicate realistic use in which only a limited effect of contact time was observed. There is a need for further investigation into which factors have the greatest impact on disinfectant towelette efficacy when applied in clinical settings.


Assuntos
Infecção Hospitalar , Desinfetantes , Humanos , Desinfetantes/farmacologia , Staphylococcus aureus , Infecção Hospitalar/prevenção & controle , Fatores de Tempo
10.
Front Psychiatry ; 14: 1173535, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304430

RESUMO

Psychological time reveals information about an individual's psychological state and psychopathological traits and, thus, has become a new perspective through which the occurrence and development of depression can be examined. Psychological time includes time perception, time perspective, circadian rhythms, and passage of time. Patients with depression are characterized by inaccurate time interval estimation, habitual negative thoughts about the past and future, evening-type circadian rhythms, and slow passage of time. Habitual negative thoughts about the past and future and evening-type circadian rhythms influence the formation of depression, and poor time interval estimation and slow passage of time may result from depression. Further study is needed accurately exploring psychological time and influencing factors in patients with depression, and prospective cohort studies could further clarify this complex relationship. In addition, the study of psychological time has important implications for developing effective interventions to reduce depression.

11.
Molecules ; 28(11)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37298734

RESUMO

The development of highly active and low-cost catalysts for use in oxygen reduction reaction (ORR) is crucial to many advanced and eco-friendly energy techniques. N-doped carbons are promising ORR catalysts. However, their performance is still limited. In this work, a zinc-mediated template synthesis strategy for the development of a highly active ORR catalyst with hierarchical porous structures was presented. The optimal catalyst exhibited high ORR performance in a 0.1 M KOH solution, with a half-wave potential of 0.89 V vs. RHE. Additionally, the catalyst exhibited excellent methanol tolerance and stability. After a 20,000 s continuous operation, no obvious performance decay was observed. When used as the air-electrode catalyst in a zinc-air battery (ZAB), it delivered an outstanding discharging performance, with peak power density and specific capacity as high as 196.3 mW cm-2 and 811.5 mAh gZn-1, respectively. Its high performance and stability endow it with potential in practical and commercial applications as a highly active ORR catalyst. Additionally, it is believed that the presented strategy can be applied to the rational design and fabrication of highly active and stable ORR catalysts for use in eco-friendly and future-oriented energy techniques.


Assuntos
Carbono , Zinco , Humanos , Porosidade , Tolerância a Medicamentos , Hipóxia , Espécies Reativas de Oxigênio , Oxigênio
12.
Molecules ; 28(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298948

RESUMO

Four previously undescribed highly oxygenated diterpenoids (1-4), zeylleucapenoids A-D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily via NMR experiments. The absolute configuration of 1 was established using theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2-4 were assigned using theoretical ORD calculations. Zeylleucapenoids A-D were tested for anti-inflammatory activity against nitric oxide (NO) production in RAW264.7 macrophages, of which only 4 showed significant efficacy with an IC50 value of 38.45 µM. Further, active compound 4 was also evaluated for the inhibition of the release of pro-inflammatory cytokines TNF-α and IL-6 and was found to have a dose-dependent inhibitory effect, while it showed nontoxic activity for zebrafish embryos. A subsequent Western blotting experiment revealed that 4 inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated that the possible mechanism of action for 4 may be bind to targets via hydrogen and hydrophobic bond interactions.


Assuntos
Diterpenos , Peixe-Zebra , Animais , Simulação de Acoplamento Molecular , Peixe-Zebra/metabolismo , Diterpenos/química , Anti-Inflamatórios/química , Óxido Nítrico/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo
13.
ACS Nano ; 17(11): 10677-10688, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37253163

RESUMO

Nanoparticle (NP) exsolution from perovskite-based oxides matrix upon reduction has emerged as an ideal platform for designing highly active catalysts for energy and environmental applications. However, the mechanism of how the material characteristics impacts the activity is still ambiguous. In this work, taking Pr0.4Sr0.6Co0.2Fe0.7Nb0.1O3 thin film as the model system, we demonstrate the critical impact of the exsolution process on the local surface electronic structure. Combining advanced microscopic and spectroscopic techniques, particularly scanning tunneling microscopy/spectroscopy and synchrotron-based near ambient X-ray photoelectron spectroscopy, we find that the band gaps of both the oxide matrix and exsolved NP decrease during exsolution. Such changes are attributed to the defect state within the forbidden band introduced by oxygen vacancies and the charge transfer across the NP/matrix interface. Both the electronic activations of oxide matrix and the exsolved NP phase lead to good electrocatalytic activity toward the fuel oxidation reaction at elevated temperature.

14.
Sci Rep ; 13(1): 5849, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-37037898

RESUMO

There has been an increase in Candida auris healthcare-associated infections, which result from cross-contamination from surfaces and equipment. In this study, we tested the efficacies of EPA-registered disinfectant towelettes products that are increasingly used for infection control against C. auris at a range of contact times following modifications to standard EPA protocol MB-33-00. Hydrogen peroxide (HP)-based disinfectant towelettes were more efficacious against C. auris than the quaternary ammonium chloride (QAC)-alcohol-based disinfectant towelettes irrespective of tested contact times. Thirty s contact time was significantly less effective in reducing C. auris compared to 1-, 2-, 3-, and 10-min contact times. However, there were no statistically significant differences in the level of disinfection among 1-min and longer contact times regardless of product chemistry. None of the products achieved a standard six-log10 reduction at any tested contact times. Overall, the HP-based disinfectant towelette was significantly more fungicidal than the QAC-alcohol-based disinfectant towelette. For all product types, 30 s contact time did not achieve the same level of disinfection as 1-min or longer contact times. Overall, disinfectant towelette efficacy is dependent upon product formulation and contact time.


Assuntos
Desinfetantes , Desinfetantes/farmacologia , Candida auris , Desinfecção/métodos , Controle de Infecções/métodos , Peróxido de Hidrogênio/farmacologia , Etanol , Cloreto de Amônio
15.
Chem Commun (Camb) ; 59(34): 5043-5046, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37013962

RESUMO

We report herein that a copper catalyst catalyzed efficient cross-coupling of aryl and alkenyl boronic acids with alkynyl-1,2-benziodoxol-3(1H)-ones to afford diaryl alkynes and enynes under mild visible light irradiation conditions using a catalytic amount of base or even in the absence of base. The reaction applies copper as the catalyst and tolerates a variety of functional moieties including aryl bromide and iodide.

16.
J Phys Chem Lett ; 14(13): 3296-3306, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36988183

RESUMO

Excess reversible lithium storage is an alternative crucial strategy besides the expansion of redox centers to boost the capacity of layered cathodes. However, the mechanism of excess Li+ intercalation is far from being comprehended, indisputably hindering the development of layered cathodes. Herein, the comparative study of Li2RuyMn1-yO3 and Li2RuyTi1-yO3 by X-ray absorption and photoemission spectroscopies attempts to illustrate the origin. The charge transfer from Ru to Mn through TM-O π bonding interaction with the formation of O holes has been revealed in Li2RuyMn1-yO3, which originates from the inductive effect and the approaching energy level of Mn and Ru bands. The electronic state is thought to reduce the Coulomb repulsion of Li+ with the matrix, promoting excess Li+ intercalation. The results are instructive to the rational design of layered cathodes to achieve a larger reversible capacity in a wide voltage window.

17.
Comput Intell Neurosci ; 2023: 3677387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824697

RESUMO

Vehicles transporting hazardous material (HAZMAT) pose a severe threat to highway safety, especially in road tunnels. Vehicle reidentification is essential for identifying and warning abnormal states of HAZMAT vehicles in road tunnels. However, there is still no public dataset for benchmarking this task. To this end, this work releases a real-world tunnel HAZMAT vehicle reidentification dataset, VisInt-THV-ReID, including 10,048 images with 865 HAZMAT vehicles and their spatiotemporal information. A method based on multimodal information fusion is proposed to realize vehicle reidentification by fusing vehicle appearance and spatiotemporal information. We design a spatiotemporal similarity determination method for vehicles based on the spatiotemporal law of vehicles in tunnels. Compared with other reidentification methods based on multimodal information fusion, i.e., PROVID, Visual + ST, and Siamese-CNN, experimental results show that our approach significantly improves the vehicle reidentification recognition precision.


Assuntos
Substâncias Perigosas , Veículos Automotores , Meios de Transporte
18.
Am J Infect Control ; 51(4): 380-387, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35868460

RESUMO

BACKGROUND: Optimization of automated floor disinfection practices using different application methods and product types is important to ensure that pathogens such as Staphylococcus aureus do not transfer from contaminated floors to other high contact areas resulting in healthcare-associated infections (HAIs). We hypothesized that there would be significant differences among the disinfectants and a cleaner under different application methods. Also, performance of application methods would be dependent upon type of product used. METHODS: We tested and compared efficacies of 5 EPA registered disinfectants and one cleaner using an automated Taski 455B floor cleaner against S aureus ATCC 6538 on 2 meters of contaminated vinyl flooring using 3 application methods. RESULTS: Hydrogen peroxide and quaternary ammonium compounds were more efficacious against S aureus than the neutral cleaner. There were no significant differences among the sampling areas tested and application methods regardless of product type. Mean log10 densities recovered from different machine parts and wastewater collected were statistically higher for the cleaner than disinfectants. CONCLUSIONS: All disinfectants had more bactericidal efficacy than the cleaner for all sampling zones on the tested floor. Overall, performance of the floor machine is dependent upon the type of product used.


Assuntos
Infecção Hospitalar , Desinfetantes , Infecções Estafilocócicas , Humanos , Desinfecção/métodos , Staphylococcus aureus , Desinfetantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Infecções Estafilocócicas/prevenção & controle
19.
Micromachines (Basel) ; 15(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38258191

RESUMO

This paper presents a novel piezoelectric micromachined ultrasonic transducer (PMUT) with theoretical simulation, fabrication, and testing. Conventional methods using a PCB or an external horn to adjust the PMUT acoustic field angle are limited by the need for transducer size. To address this limitation, the stepped-tube (expanded tube) backside cavity PMUT has been proposed. The stepped-tube PMUT and the tube PMUT devices have the same membrane structure, and the acoustic impedance matching of the PMUT is optimized by modifying the boundary conditions of the back cavity structure. The acoustic comparison experiments show that the average output sound pressure of the stepped-tube backside cavity PMUT has increased by 17%, the half-power-beam-width (θ-3db) has been reduced from 55° to 30° with a reduction of 45%, and the side lobe level signal is reduced from 147 mV to 66 mV. In addition, this work is fabricated on an eight-inch wafer. The process is compatible with standard complementary metal oxide semiconductor (CMOS), conditions are stable, and the cost is controllable, plus it facilitates the batch process. These conclusions suggest that the stepped-tube backside cavity PMUT will bring new, effective, and reliable solutions to ranging applications.

20.
Molecules ; 27(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36558100

RESUMO

Acetaminophen (APAP) toxicity is a common cause of hepatic failure, and the development of effective therapy is still urgently needed. Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, has been identified as a master gene for regulating enterohepatic metabolic homeostasis and has proven to be a promising drug target for various liver diseases. Through high-throughput chemical screening, the natural product 2-oxokolavenol was identified as a novel and selective FXR agonist. Further investigations revealed that 2-oxokolavenol exerts therapeutic efficacy against APAP-induced hepatocyte damage in an FXR-dependent manner. Mechanistically, 2-oxokolavenol forms two hydrogen bonds with M265 and Y369 of human FXR to compatibly fit into the ligand binding pocket of FXR, which potently leads to the recruitment of multiple co-regulators and selectively induces the transcriptional activity of FXR. Our findings thus not only reveal the direct target of natural product 2-oxokolavenol, but also provide a promising hit compound for the design of new FXR modulators with potential clinical value.


Assuntos
Acetaminofen , Hepatopatias , Humanos , Acetaminofen/metabolismo , Hepatopatias/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fígado
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