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2.
J Hazard Mater ; 471: 134411, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38677117

RESUMEN

The spatial patterns of pollutants produced by industrial parks are affected by many factors, but the interactions among polycyclic aromatic hydrocarbons (PAHs), metals, and soil microorganisms in the valley landforms of the Tibetan Plateau are poorly understood. Thus, this study systematically investigated the distribution and pollution of metals and PAHs in soil around an industrial park in the typical valley landform of the Tibetan Plateau and analyzed and clarified the interaction among metals, PAHs, and microorganisms. The results were as follows: metal and PAH concentrations were affected by wind direction, especially WN-ES and S-N winds; Cd (2.86-54.64 mg·kg-1) had the highest soil concentrations of the metals screened, followed by variable concentrations of Cu, Pb, and Zn; the pollution levels of metals and PAHs in the S-N wind direction were lower than those in the WN-ES wind direction; the Cd content of Avena sativa in the agricultural soil around the factory exceeded its enrichment ability and food safety standards; the closer to the center of the park, the higher the ecological risk of PAHs; and the TEQ and MEQ values of the PAHs were consistent with their concentration distributions. The results of the soil microbial diversity and co-occurrence network in the dominant wind direction showed that metal and PAH pollution weakened the robustness of soil microbial communities. Additionally, the diversity and robustness of soil microbial communities at the S wind site were higher than those at the ES wind site, which might be attributed to the lower metal content of the former than the latter, which plays a negative role in the biodegradation of PAHs. The results of this study provide insights into the site selection, pollutant supervision, and environmental remediation of industrial parks in typical landforms.


Asunto(s)
Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos , Microbiología del Suelo , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/análisis , Tibet , Viento , Metales/análisis , Suelo/química , Metales Pesados/análisis
3.
RSC Adv ; 14(18): 12303-12312, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38633496

RESUMEN

As dienes contain two C[double bond, length as m-dash]C bonds, theoretically, they are much more chemically reactive with hydroxyl radical (˙OH) than alkenes and alkanes, and the reaction with ˙OH is one of the main atmospheric degradation routes of dienes during the daytime. In our work, rate coefficients of three types of acyclic dienes: conjugated as 3-methyl-1,3-pentadiene (3M13PD), isolated as 1,4-hexadiene (14HD), and cumulated as 1,2-pentadiene (12PD) reaction with ˙OH were measured in the temperature range of 273-318 K and 1 atm using the relative rate method. At 298 ± 3 K, the rate coefficients for those reactions were determined to be k3M13PD+OH = (15.09 ± 0.72) × 10-11, k14HD+OH = (9.13 ± 0.62) × 10-11, k12PD+OH = (3.34 ± 0.40) × 10-11 (as units of cm3 per molecule per s), in the excellent agreement with values of previously reported. The first measured temperature dependence for 3M13PD, 14HD and 12PD reaction with ˙OH can be expressed by the following Arrhenius expressions in units of cm3 per molecule per s: k3M13PD+OH = (8.10 ± 2.23) × 10-11 exp[(173 ± 71)/T]; k14HD+OH = (9.82 ± 5.10) × 10-12 exp[(666 ± 123)/T]; k12PD+OH = (1.13 ± 0.87) × 10-12 exp[(1038 ± 167)/T] (as units of cm3 per molecule per s). The kinetic discussion revealed that the relative position between these two C[double bond, length as m-dash]C could significantly affect the reactivity of acyclic dienes toward ˙OH. A simple structure-activity relationship (SAR) method was proposed to estimate the reaction rate coefficients of acyclic dienes with ˙OH.

4.
J Colloid Interface Sci ; 665: 477-490, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38429120

RESUMEN

Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo. Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Nanopartículas , Neoplasias Pancreáticas , Humanos , Glutamina/farmacología , Glutamina/metabolismo , Glutamina/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/uso terapéutico , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/uso terapéutico , Glucólisis , Fototerapia , Línea Celular Tumoral
5.
Nanomaterials (Basel) ; 14(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38535690

RESUMEN

Flexible thermoelectric generators (FTEGs), which can overcome the energy supply limitations of wearable devices, have received considerable attention. However, the use of toxic Te-based materials and fracture-prone electrodes constrains the application of FTEGs. In this study, a novel Ag2Se and Poly (3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT:PSS)/multi-walled carbon nanotube (MWCNT) FTEG with a high output performance and good flexibility is developed. The thermoelectric columns formulated in the work are environmentally friendly and reliable. The key enabler of this work is the use of embedded EGaIn electrodes, which increase the temperature difference collected by the thermoelectric column, thereby improving the FTEG output performance. Additionally, the embedded EGaIn electrodes could be directly printed on polydimethylsiloxane (PDMS) molds without wax paper, which simplifies the preparation process of FTEGs and enhances the fabrication efficiency. The FTEG with embedded electrodes exhibits the highest output power density of 25.83 µW/cm2 and the highest output power of 10.95 µW at ΔT = 15 K. The latter is 31.6% higher than that of silver-based FTEGs and 2.5% higher than that of covered EGaIn-based FTEGs. Moreover, the prepared FTEG has an excellent flexibility (>1500 bends) and output power stability (>30 days). At high humidity and high temperature, the prepared FTEG maintains good performance. These results demonstrate that the prepared FTEGs can be used as a stable and environmentally friendly energy supply for wearable devices.

6.
Nanoscale ; 16(15): 7427-7436, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38525943

RESUMEN

Screen-printed interdigital electrode-based flexible pressure sensor arrays play a crucial role in human-computer interaction and health monitoring due to their simplicity of fabrication. However, the long-standing challenge of how to reduce the number of electrical output ports of interdigital electrodes to facilitate integration with back-end circuits is still commonly ignored. Here, we propose a screen-printing strategy to avoid wire cross-planes for rapid fabrication of flexible pressure sensor arrays. By innovatively introducing an insulating ink to realize electrical insulation and three-dimensional interconnection of wire crossings, the improved sensor array (4 × 4) successfully reduces the number of output ports from 17 to 8. In addition, we further constructed microstructures on the laser-etched electrode surfaces and the sensitive layer, which enabled the sensor to achieve a sensitivity as high as 17 567.5 kPa-1 in the range of 0-50 kPa. Moreover, we integrated the sensors with back-end circuits for the precise detection of tactile and physiological information. This provides a reliable method for preparing high-performance flexible sensor arrays and large-scale integration of microsensors.

7.
Micromachines (Basel) ; 15(2)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38398904

RESUMEN

In the field of in situ measurement of high-temperature pressure, fiber-optic Fabry-Perot pressure sensors have been extensively studied and applied in recent years thanks to their compact size and excellent anti-interference and anti-shock capabilities. However, such sensors have high technological difficulty, limited pressure measurement range, and low sensitivity. This paper proposes a fiber-optic Fabry-Perot pressure sensor based on a membrane-hole-base structure. The sensitive core was fabricated by laser cutting technology and direct bonding technology of three-layer sapphire and develops a supporting large-cavity-length demodulation algorithm for the sensor's Fabry-Perot cavity. The sensor exhibits enhanced sensitivity, a simplified structure, convenient preparation procedures, as well as improved pressure resistance and anti-harsh environment capabilities, and has large-range pressure sensing capability of 0-10 MPa in the temperature range of 20-370 °C. The sensor sensitivity is 918.9 nm/MPa, the temperature coefficient is 0.0695 nm/(MPa∙°C), and the error over the full temperature range is better than 2.312%.

8.
Micromachines (Basel) ; 15(2)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38398909

RESUMEN

The emerging field of flexible tactile sensing systems, equipped with multi-physical tactile sensing capabilities, holds vast potential across diverse domains such as medical monitoring, robotics, and human-computer interaction. In response to the prevailing challenges associated with the limited integration and sensitivity of flexible tactile sensors, this paper introduces a versatile tactile sensing system capable of concurrently monitoring temperature and pressure. The temperature sensor employs carbon nanotube/graphene conductive paste as its sensitive material, while the pressure sensor integrates an ionic gel containing boron nitride as its sensitive layer. Through the application of cost-effective screen printing technology, we have successfully manufactured a flexible dual-mode sensor with exceptional performance, featuring high sensitivity (804.27 kPa-1), a broad response range (50 kPa), rapid response time (17 ms), and relaxation time (34 ms), alongside exceptional durability over 5000 cycles. Furthermore, the resistance temperature coefficient of the sensor within the temperature range of 12.5 °C to 93.7 °C is -0.17% °C-1. The designed flexible dual-mode tactile sensing system enables the real-time detection of pressure and temperature information, presenting an innovative approach to electronic skin with multi-physical tactile sensing capabilities.

9.
Front Psychiatry ; 15: 1280935, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38374979

RESUMEN

Introduction: Depression is a prevalent mental illness that is primarily diagnosed using psychological and behavioral assessments. However, these assessments lack objective and quantitative indices, making rapid and objective detection challenging. In this study, we propose a novel method for depression detection based on eye movement data captured in response to virtual reality (VR). Methods: Eye movement data was collected and used to establish high-performance classification and prediction models. Four machine learning algorithms, namely eXtreme Gradient Boosting (XGBoost), multilayer perceptron (MLP), Support Vector Machine (SVM), and Random Forest, were employed. The models were evaluated using five-fold cross-validation, and performance metrics including accuracy, precision, recall, area under the curve (AUC), and F1-score were assessed. The predicted error for the Patient Health Questionnaire-9 (PHQ-9) score was also determined. Results: The XGBoost model achieved a mean accuracy of 76%, precision of 94%, recall of 73%, and AUC of 82%, with an F1-score of 78%. The MLP model achieved a classification accuracy of 86%, precision of 96%, recall of 91%, and AUC of 86%, with an F1-score of 92%. The predicted error for the PHQ-9 score ranged from -0.6 to 0.6.To investigate the role of computerized cognitive behavioral therapy (CCBT) in treating depression, participants were divided into intervention and control groups. The intervention group received CCBT, while the control group received no treatment. After five CCBT sessions, significant changes were observed in the eye movement indices of fixation and saccade, as well as in the PHQ-9 scores. These two indices played significant roles in the predictive model, indicating their potential as biomarkers for detecting depression symptoms. Discussion: The results suggest that eye movement indices obtained using a VR eye tracker can serve as useful biomarkers for detecting depression symptoms. Specifically, the fixation and saccade indices showed promise in predicting depression. Furthermore, CCBT demonstrated effectiveness in treating depression, as evidenced by the observed changes in eye movement indices and PHQ-9 scores. In conclusion, this study presents a novel approach for depression detection using eye movement data captured in VR. The findings highlight the potential of eye movement indices as biomarkers and underscore the effectiveness of CCBT in treating depression.

10.
Sci Total Environ ; 915: 170115, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38232848

RESUMEN

Grafting is an effective horticultural method to reduce Cd accumulation in crops. However, the mechanism of grafting inducing the decrease in Cd content in scions remains unclear. This study evaluated the effect of grafting on fruit quality, yield, and Cd content of Solanum melongena, and explored the potential mechanism of grafting reducing Cd content in scions. In the low Cd-contaminated soil, compared with un-grafted (UG) and self-grafted plants (SG), the fruit yield of inter-grafted plants (EG) increased by 38 %, and the fruit quality was not markedly affected. In EG, the decrease in total S and Cd content was not related to organic acids and thiol compounds. The decrease in total S and Cd content in EG leaves and fruits was closely related to the synthesis and transportation of glucosinolates (GSL). The genes encoding GSL synthesis in leaves, such as basic helix-loop-helix, myelocytomatosis proteins, acetyl-CoA, cytochrome P450, and glutathione S-transferases, were significantly downregulated. In EG leaves, the contents of five of the eight amino acids involved in GSL synthesis decreased significantly (P < 0.05). Notably, total GSL in EG stems, leaves, and fruits had a significant linear correlation with total S and Cd. In summary, the decrease in total S and Cd content in scions caused by grafting is closely related to GSL. Our findings provide a theoretical basis for the safe use of Cd-contaminated soil, exploring the long-distance transport of Cd in plants and cultivating crops with low Cd accumulation.


Asunto(s)
Contaminantes del Suelo , Solanum melongena , Cadmio/análisis , Solanum melongena/metabolismo , Glucosinolatos/análisis , Antioxidantes/metabolismo , Suelo , Contaminantes del Suelo/análisis , Raíces de Plantas/metabolismo
11.
IEEE J Biomed Health Inform ; 28(2): 753-764, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37027681

RESUMEN

Chest imaging plays an essential role in diagnosing and predicting patients with COVID-19 with evidence of worsening respiratory status. Many deep learning-based approaches for pneumonia recognition have been developed to enable computer-aided diagnosis. However, the long training and inference time makes them inflexible, and the lack of interpretability reduces their credibility in clinical medical practice. This paper aims to develop a pneumonia recognition framework with interpretability, which can understand the complex relationship between lung features and related diseases in chest X-ray (CXR) images to provide high-speed analytics support for medical practice. To reduce the computational complexity to accelerate the recognition process, a novel multi-level self-attention mechanism within Transformer has been proposed to accelerate convergence and emphasize the task-related feature regions. Moreover, a practical CXR image data augmentation has been adopted to address the scarcity of medical image data problems to boost the model's performance. The effectiveness of the proposed method has been demonstrated on the classic COVID-19 recognition task using the widespread pneumonia CXR image dataset. In addition, abundant ablation experiments validate the effectiveness and necessity of all of the components of the proposed method.


Asunto(s)
COVID-19 , Neumonía , Humanos , Rayos X , Neumonía/diagnóstico por imagen , COVID-19/diagnóstico por imagen , Tórax/diagnóstico por imagen , Diagnóstico por Computador
12.
Analyst ; 149(3): 768-777, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38108435

RESUMEN

Long nanosecond pulses have been proven to be efficient at enhancing underwater LIBS emission. However, the quantitative analytical capability of underwater long-pulse LIBS has yet to be further revealed. In this work, we investigated the spectral characteristics by irradiating with a laser pulse of 120 ns duration. The alkali and alkaline earth metals Li, K and Ca and the transition element Mn were selected for analysis. It is shown that obvious self-reversal structures were observed in the spectra at high concentrations, making the calibration curves saturated. Correction was performed using the approximate Voigt function fitting method, which significantly improves the linearity of the calibration curves. In addition to the target metal elements, atomic lines of the matrix elements H and O in water were also observed, which can serve as promising internal standards for quantitative analysis. A comparison of the quantification performance with and without the internal standards demonstrates that the use of the internal standards is conducive to improving the robustness of the calibration approaches with higher determination coefficients. More importantly, the underwater LIBS signal stability is improved by more than 3 times, and the prediction error for validation samples is reduced by 2-4 times. The present results suggest that long ns pulses are favorable to significantly improving the qualitative and quantitative performance of underwater single-pulse LIBS, enabling long-pulse LIBS to have great potential to be applied to underwater in situ chemical analysis.

13.
Micromachines (Basel) ; 14(10)2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37893313

RESUMEN

Membrane-free acoustic sensors based on new principle and structure are becoming a research hotspot, because of many advantages, e.g., their wide bandwidth and high sensitivity. It is proposed that a membrane-free acoustic sensor employs a semi-buried optical waveguide ring resonator (SOWRR) as a sensing element. Using air as the upper cladding medium, the excited evanescent field in the air cladding medium would be modulated by acoustic wave. On this basis, the acoustic sensing model is established. Taking high Q factor and resonance depth as design criteria, the optimal design parameters are given. The optimal values of the air/SiO2: Ge/SiO2 waveguide resonator length and coupling spacing are obtained as 50 mm and 5.6 µm, respectively. The Q factor of the waveguide resonator of this size is as high as 8.33 × 106. The theoretical simulation indicates that the frequency response ranges from 1 Hz to 1.58 MHz and that the minimum detectable sound pressure is 7.48 µPa using a laser with linewidth of 1 kHz. Because of its advantages of wide bandwidth and high sensitivity, the membrane-free sensor is expected to become one of the most promising candidates for the next-generation acoustic sensor.

14.
Opt Express ; 31(18): 29994-30004, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37710788

RESUMEN

The sensors with a wide gas pressure detection range are urgently demanded in many industrial applications. Here, we propose a gas pressure sensor based on an all-solid open Fabry-Pérot interferometer, which is prepared by using optical contact bonding to ensure high structural strength and high-quality factor of 8.8 × 105. The applied pressure induces a change in the refractive index of the air, leading to the shift of the resonant spectrum. The pressure is detected by calibrating this shift. The sensor exhibits a pressure sensitivity of 4.20 ± 0.01 nm/MPa in a pressure range of 0 to 10 MPa and has a minimum pressure resolution of 0.005 MPa. Additionally, it shows a lower temperature cross-sensitivity of -0.25 kPa/°C. These findings affirm that the sensor achieves high-sensitivity pressure sensing across a wide detection range. Moreover, owing to its exceptional mechanical strength, it holds great promise for applications in harsh environments, such as high temperature and high pressure.

15.
Nat Commun ; 14(1): 5004, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37591889

RESUMEN

MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal "RF/RY" motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the G6.48XP6.50F6.51G6.52X(2)F/W6.55 motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.


Asunto(s)
Receptores Acoplados a Proteínas G , Transducción de Señal , Humanos , Citoplasma , Citosol , Ligandos , Prurito
16.
Sci Total Environ ; 903: 166329, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-37633398

RESUMEN

Extreme hydrological events have become increasingly frequent on a global scale. The middle Yangtze River also faces a substantial challenge in dealing with extreme flooding and drought. However, the long-term characteristics of the extreme hydrological regime have not yet been adequately recognized. Moreover, there is uncertainty in the extreme value estimation, and this uncertainty needs to be distinguished and quantified. In this study, we investigated the nonstationary frequency characteristics of extreme low lake levels (ELLLs), taking the Poyang Lake as an example. Daily lake levels from 1960 to 2022 were utilized to estimate the return level using the generalized Pareto distribution (GPD). The uncertainty from three sources, i.e., the parameter estimator, threshold selection, and covariate, was quantified via variance decomposition. The results indicate that (1) the parameter estimator is the predominant source of uncertainty, with a contribution rate of approximately 87 %. The total uncertainty of the covariate, threshold, and interaction term is only 13 %. (2) Two indexes, namely the annual minimum water level (WLmin) and the days with peak over the 90 % threshold per year (DPOT90), decreased (0.01-0.03 m/year) and increased (0.17-1.39 days/year), respectively, indicating a progressively severe drought trend for Poyang Lake. (3) The return level with return period of 5 to 100 years significantly decreased after the early 21st century. A large spatial heterogeneity was identified for the variation in the return level, and the change rate of the return level with a 100-year return period ranged from 5 % to 40 % for the whole lake. (4) The ELLLs had a stronger correlation with the catchment discharge than with the Yangtze River discharge and the large-scale atmospheric circulation indices. This study provides a methodology with reduced uncertainty for nonstationary frequency analysis (NFA) of ELLLs exemplified in large river-lake systems.

17.
Sensors (Basel) ; 23(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37447910

RESUMEN

In this work, a capacitive pH sensor consisting of Ta2O5 functional film is designed and fabricated by employing MEMS-based procedures. The Ta2O5 thin film has an amorphous microstructure, and its surface roughness is less than 3.17 nm. A signal processing circuit and a software filtering algorithm are also designed to measure the pH value, thus improving the detection accuracy and anti-interference ability. Good linearity (R2 = 0.99904) and sensitivity (63.12 mV/pH) are recorded for the proposed sensing element in the range of pH 2~12. In addition, the sensor's drift and hysteresis are equal to 5.1 mV and 5.8 mV, respectively. The enhanced sensing performance in combination with the facile miniaturization process, low fabrication cost, and suitability for mass production render the fabricated sensor attractive for applications where pH change measurements in a water environment are required.


Asunto(s)
Sistemas Microelectromecánicos , Algoritmos , Concentración de Iones de Hidrógeno
18.
Proc Natl Acad Sci U S A ; 120(30): e2216329120, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37478163

RESUMEN

To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, Sci STKE 2001, re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402, 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390, 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that Gs-biased signaling, but not Gi activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-Gi, EP4-Gs, and EP4-Gi in complex with endogenous prostaglandin E2 (PGE2)or two synthetic agonists and comparing with PGE2-EP2-Gs structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the Gs/Gi transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their Gs/Gi coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for Gs/Gi coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.


Asunto(s)
Dinoprostona , Transducción de Señal , Dinoprostona/metabolismo , Transducción de Señal/fisiología , Receptores de Prostaglandina/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Hormonas , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Subtipo EP2 de Receptores de Prostaglandina E/metabolismo , Subtipo EP3 de Receptores de Prostaglandina E/metabolismo
19.
J Hazard Mater ; 457: 131811, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37307733

RESUMEN

Graphene oxide (GO)-promoted microbial degradation technology is considered an important strategy to eliminate polycyclic aromatic hydrocarbons (PAHs) in the environment; however, the mechanism by which GO affects microbial degradation of PAHs has not been fully studied. Thus, this study aimed to analyze the effect of GO-microbial interaction on PAHs degradation at the microbial community structure, community gene expression, and metabolic levels using multi-omics combined technology. We treated PAHs-contaminated soil samples with different concentrations of GO and analyzed the soil samples for microbial diversity after 14 and 28 days. After a short exposure, GO reduced the diversity of soil microbial community but increased potential degrading microbial abundance, promoting PAHs biodegradation. This promotion effect was further influenced by the GO concentration. In a short period of time, GO upregulated the expression of genes involved in microbial movement (flagellar assembly), bacterial chemotaxis, two-component system, and phosphotransferase system in the soil microbial community and increased the probability of microbial contact with PAHs. Biosynthesis of amino acids and carbon metabolism of microorganisms were accelerated, thereby increasing the degradation of PAHs. With the extension of time, the degradation of PAHs stagnated, which may be due to the weakened stimulation of GO on microorganisms. The results showed that screening specific degrading microorganisms, increasing the contact area between microorganisms and PAHs, and prolonging the stimulation of GO on microorganisms were important means to improve the biodegradation efficiency of PAHs in soil. This study elucidates how GO affects microbial PAHs degradation and provides important insights for the application of GO-assisted microbial degradation technology.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Hidrocarburos Policíclicos Aromáticos/análisis , Microbiología del Suelo , Biodegradación Ambiental , Suelo/química
20.
J Control Release ; 360: 468-481, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37391031

RESUMEN

Tumor angiogenesis and cancer stem cells (CSCs) are two major hallmarks of solid tumors. They have long received attention for their critical roles in tumor progression, metastasis and recurrence. Meanwhile, plenty of evidence indicates the close association between CSCs and tumor vasculature. CSCs are proven to promote tumor angiogenesis, and the highly vascularized tumor microenvironment further maintains CSCs growth in return, thereby forming a hard-breaking vicious circle to promote tumor development. Hence, though monotherapy targeting tumor vasculature or CSCs has been extensively studied over the past decades, the poor prognosis has been limiting the clinical application. This review summarizes the crosstalk between tumor vasculature and CSCs with emphasis on small-molecule compounds and the associated biological signaling pathways. We also highlight the importance of linking tumor vessels to CSCs to disrupt the CSCs-angiogenesis vicious circle. More precise treatment regimens targeting tumor vasculature and CSCs are expected to benefit future tumor treatment development.


Asunto(s)
Neoplasias , Humanos , Neoplasias/terapia , Neovascularización Patológica/patología , Células Madre Neoplásicas/metabolismo , Microambiente Tumoral
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