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1.
Artículo en Inglés | MEDLINE | ID: mdl-38969882

RESUMEN

The construction of ecological security pattern (ESP) holds paramount importance in ensuring regional environment sustainability. This study introduces an innovative approach to ESP construction grounded in landscape ecological risk (LER) assessment, with Wu-Chang-Shi urban agglomeration in Xinjiang, China, serving as a case study. Initially, LER within the area was evaluated using the LER Index (LERI) method. Subsequently, the Geodetector model was employed to discern the relationship between multi-source data and LER. Furthermore, ecological resistance and corridors were delineated utilizing the minimum cumulative resistance (MCR) model. Lastly, the corridors were optimized using the gravity model, finalizing the ESP construction. Study results reveal that LER was always fluctuating from 1990 to 2010, and tended to stabilize from 2010 to 2020. Factor detection underscores the predominant influence of land use on LER, followed by elevation and vegetation distribution. The ESP shows the imperative for improving connectivity of the natural areas that are fragmented by urban land, highlighting the great significance of the woodland-originating corridors. Finally, strategies are proposed to enhance woodland and water coverage, boost landscape diversity in nature reserves, and prioritize ecological conservation in corridor regions. In summation, the study furnishes a framework for analyzing arid regions in Eurasia. Furthermore, the research idea of evaluation-analysis-remodeling also offers insights into environmental management in developing areas with more diverse climate types.

2.
Mol Biotechnol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38890219

RESUMEN

The stress resistance of medicinal plants is essential to the accumulation of pharmacological active ingredients, but the regulation mechanism of biological factors and abiotic factors on medicinal plants is still unclear. To investigate the mechanism of soil nutrient and microecology on the stress resistance of C. pilosula, rhizosphere soil and roots were collected across the four seasons in Minxian, Gansu, and their physicochemical properties, as well as root-associated microorganisms, were examined. The results showed that the bacterial α-diversity indexes increased in the endosphere and rhizosphere from summer to autumn. At the same time, the community composition and function changed considerably. The stability of the endophytic bacterial community was higher than that rhizospheric bacteria, and the complexity of the endophytic bacterial community was lower than rhizospheric bacteria. Soil organic matter (OM), water content (WC), total potassium (TK), and total nitrogen (TN) have been identified as the key factors affecting bacterial community diversity and stress resistance of C. pilosula. WC, TN, and OM showed significant differences from summer to autumn (P < 0.5). Four key soil physiochemical factors changed significantly between seasons (P < 0.01). TN and OM change the stress resistance of C. pilosula mainly by changing the activity of antioxidant enzymes. Changes of OM and endophytic bacterial diversity affect the accumulation of soluble sugars to alter stress resistance. These four key soil physicochemical factors significantly influenced the diversity of endophytic bacteria. WC and OM were identified as the most important factors for endophytic and rhizospheric bacteria, respectively. This study provided the research basis for the scientific planting of C. pilosula.

3.
J Cell Physiol ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38922861

RESUMEN

Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, which affects the patients' quality of life and health and imposes a significant socioeconomic burden. Despite great efforts made by researchers to understand the pathogenesis of IDD, effective strategies for preventing and treating this disease remain very limited. Sirtuins are a highly conserved family of (NAD+)-dependent deacetylases in mammals that are involved in a variety of metabolic processes in vivo. In recent years, sirtuins have attracted much attention owing to their regulatory roles in IDD on physiological activities such as inflammation, apoptosis, autophagy, aging, oxidative stress, and mitochondrial function. At the same time, many studies have explored the therapeutic effects of sirtuins-targeting activators or micro-RNA in IDD. This review summarizes the molecular pathways of sirtuins involved in IDD, and summarizes the therapeutic role of activators or micro-RNA targeting Sirtuins in IDD, as well as the current limitations and challenges, with a view to provide possible solutions for the treatment of IDD.

4.
ChemSusChem ; : e202400413, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38702956

RESUMEN

Continuous flow synthesis is pivotal in dye production to address batch-to-batch variations. However, synthesizing water-insoluble dyes in an aqueous system poses a challenge that can lead to clogging. This study successfully achieved the safe and efficient synthesis of azo dyes by selecting and optimizing flow reactor modules for different reaction types in the two-step reaction and implementing cascade cooperation. Integrating continuous flow microreactor with continuous stirred tank reactor (CSTR) enabled the continuous flow synthesis of Sudan Yellow 3G without introducing water-soluble functional groups or using organic solvents to enhance solubility. Optimizing conditions (acidity/alkalinity, temperature, residence time) within the initial modular continuous flow reactor resulted in a remarkable 99.5% isolated yield, 98.6 % purity, and a production rate of 2.90 g h-1. Scaling-up based on different reactor module characteristics further increased the production rate to 74.4 g h-1 while maintaining high yield and purity. The construction of this small 3D-printing modular cascaded reactor and process scaling-up provide technical support for continuous flow synthesis of water-insoluble dyes, particularly high-market-share azo dyes. Moreover, this versatile methodology proves applicable to continuous flow processes involving various homogeneous and heterogeneous reaction cascades.

5.
Neurosci Lett ; 832: 137800, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38697601

RESUMEN

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.


Asunto(s)
Lipopolisacáridos , Microglía , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , Microglía/metabolismo , Microglía/efectos de los fármacos , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Inflamación/metabolismo , Inflamación/inducido químicamente , Ratones Endogámicos C57BL
6.
Materials (Basel) ; 17(10)2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38793520

RESUMEN

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

7.
Bone ; 182: 117052, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38408588

RESUMEN

Postmenopausal osteoporosis is recognized to be one of the major skeleton diseases strongly associated with impaired bone formation. Previous reports have indicated that the importance of bone morphogenetic protein (BMP) signaling of osteoblast lineage in bone development via classical Smad signaling, however, its critical role in osteoporosis is still not well understood. In the current study, we aim to investigate the pathological role of BMPR1A, a key receptor of BMPs, in osteoporosis and its underlying mechanism. We first found that knockdown of BMPR1A by using Col1a1-creER in osteoblasts mitigated early bone loss of osteoporosis in mice, yet along with late bone maturation defects by reducing mineral adherence rate and bone formation rate in vivo. At the cellular level, we then observed that BMPR1A deficiency promoted the proliferation of pre-osteoblasts under osteoporotic conditions but hindered their late-stage mineralization. We finally elucidated that BMPR1A deficiency compensatorily triggered mTOR-autophagy perturbation by a higher level in early osteoporotic pre-osteoblasts thus resulting in the enhancement of transient cell proliferation but impairment of final mineralization. Taken together, this study indicated the significance of BMPR1A-mTOR/autophagy axis, as a double-edged sword, in osteoporotic bone formation and provided new cues for therapeutic strategies in osteoporosis.


Asunto(s)
Osteoporosis , Transducción de Señal , Ratones , Animales , Proteínas Morfogenéticas Óseas/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoblastos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Autofagia
8.
Environ Sci Technol ; 58(8): 3812-3822, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38358300

RESUMEN

Fog harvesting is considered a promising freshwater collection strategy for overcoming water scarcity, because of its environmental friendliness and strong sustainability. Typically, fogging occurs briefly at night and in the early morning in most arid and semiarid regions. However, studies on water collection from short-term fog are scarce. Herein, we developed a patterned surface with highly hydrophilic interconnected microchannels on a superhydrophobic surface to improve droplet convergence driven by the Young-Laplace pressure difference. With a rationally designed surface structure, the optimized water collection rate from mild fog could reach up to 67.31 g m-2 h-1 (6.731 mg cm-2 h-1) in 6 h; this value was over 130% higher than that observed on the pristine surface. The patterned surface with interconnected microchannels significantly shortened the startup time, which was counted from the fog contact to the first droplet falling from the fog-harvesting surface. The patterned surface was also facilely prepared via a controllable strategy combining laser ablation and chemical vapor deposition. The results obtained in outdoor environments indicate that the rationally designed surface has the potential for short-term fog harvesting. This work can be considered as a meaningful attempt to address the practical issues encountered in fog-harvesting research.


Asunto(s)
Agua Dulce , Agua , Gases , Presión , Tiempo (Meteorología) , Interacciones Hidrofóbicas e Hidrofílicas
9.
Appl Opt ; 63(1): 210-220, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175023

RESUMEN

Fringe projection profilometry (FPP) is widely used in 3D vision measurement because of its high robustness and measurement accuracy. In the case of HDR objects, due to the problem of surface reflectivity, the obtained image will be overexposed. This will cause the sinusoidality of the fringes projected on the surface of the object in the acquired image to be interfered, resulting in a phase error in the calculated wrapped phase. Therefore, a polarization-encoded sinusoidal structured light is proposed to enhance the sinusoidality of the fringe. The phase information contained in the polarized sinusoidal structured light fringe is only related to the polarization state, not to the light intensity. A polarization coding assisted structured light measurement strategy (PASM) is proposed. This method uses polarization coding assisted polarization phase-shifting fringes for phase unwrapping. The angle of the linear polarizer is set to zero in this method, and it does not require rotating the polarizer. It only needs a single exposure to improve the fringe quality and obtain a more stable unwrapping phase. The experimental results show that the obtained polarization fringes have better sinusoidality, and the phase unwrapping can be more accurate. The reconstructed 3D point cloud also does not appear missing and has better accuracy. It is a reliable method for vision measurement of HDR objects.

10.
PLoS Comput Biol ; 19(12): e1011677, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38055721

RESUMEN

RNA modification is a post transcriptional modification that occurs in all organisms and plays a crucial role in the stages of RNA life, closely related to many life processes. As one of the newly discovered modifications, N1-methyladenosine (m1A) plays an important role in gene expression regulation, closely related to the occurrence and development of diseases. However, due to the low abundance of m1A, verifying the associations between m1As and diseases through wet experiments requires a great quantity of manpower and resources. In this study, we proposed a computational method for predicting the associations of RNA methylation and disease based on graph convolutional network (RMDGCN) with attention mechanism. We build an adjacency matrix through the collected m1As and diseases associations, and use positive-unlabeled learning to increase the number of positive samples. By extracting the features of m1As and diseases, a heterogeneous network is constructed, and a GCN with attention mechanism is adopted to predict the associations between m1As and diseases. The experimental results indicate that under a 5-fold cross validation, RMDGCN is superior to other methods (AUC = 0.9892 and AUPR = 0.8682). In addition, case studies indicate that RMDGCN can predict the relationships between unknown m1As and diseases. In summary, RMDGCN is an effective method for predicting the associations between m1As and diseases.


Asunto(s)
Aprendizaje , Metilación de ARN , ARN/genética , Proyectos de Investigación , Biología Computacional , Algoritmos
11.
Radiat Res ; 200(6): 556-568, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37874034

RESUMEN

Ionizing radiation in space, radiation devices or nuclear disasters are major threats to human health and public security. Expanding countermeasures for dealing with accidental or occupational radiation exposure is crucial for the protection of radiation injuries. Circulating microRNAs (miRNAs) have emerged as promising radiation biomarkers in recent years. However, the origin, distribution and functions of radiosensitive circulating miRNAs remain unclear, which obstructs their clinical applications in the future. In this study, we found that mmu-miR-342-3p (miR-342) in mouse serum presents a stable and significant decrease after X-ray total-body irradiation (TBI). Focusing on this miRNA, we investigated the influences of circulating miR-342 on the radiation-induced injury. Through tail vein injection of Cy5-labeled synthetic miR-342, we found the exogenous miR-342-Cy5 was mainly enriched in metabolic and immune organs. Besides, the bioinformatic analysis predicted that miR-342 might involve in immune-related processes or pathways. Further, mice were tail vein injected with synthetic miR-342 mimetics (Ago-miR-342) after irradiation to upregulate the level of miR-342 in circulating blood. The results showed that the upregulation of circulating miR-342 alleviated the radiation-induced depletion of CD3+CD4+ T lymphocytes and influenced the levels of IL-2 and IL-6 in irradiated mice. Moreover, the injection of Ago-miR-342 improved the survival rates of mice with acute radiation injury. Our findings demonstrate that upregulation of circulating miR-342 alleviates the radiation-induced immune system injury, which provides us new insights into the functions of circulating miRNAs and the prospect as the targets for mitigation of radiation injuries.


Asunto(s)
MicroARN Circulante , MicroARNs , Traumatismos por Radiación , Animales , Ratones , Biomarcadores , MicroARN Circulante/genética , MicroARN Circulante/metabolismo , Sistema Inmunológico/efectos de la radiación , MicroARNs/genética , Traumatismos por Radiación/genética
12.
Microsyst Nanoeng ; 9: 129, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37829158

RESUMEN

Exhaled breath analysis has attracted considerable attention as a noninvasive and portable health diagnosis method due to numerous advantages, such as convenience, safety, simplicity, and avoidance of discomfort. Based on many studies, exhaled breath analysis is a promising medical detection technology capable of diagnosing different diseases by analyzing the concentration, type and other characteristics of specific gases. In the existing gas analysis technology, the electronic nose (eNose) analysis method has great advantages of high sensitivity, rapid response, real-time monitoring, ease of use and portability. Herein, this review is intended to provide an overview of the application of human exhaled breath components in disease diagnosis, existing breath testing technologies and the development and research status of electronic nose technology. In the electronic nose technology section, the three aspects of sensors, algorithms and existing systems are summarized in detail. Moreover, the related challenges and limitations involved in the abovementioned technologies are also discussed. Finally, the conclusion and perspective of eNose technology are presented.

13.
Appl Opt ; 62(7): 1695-1703, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37132916

RESUMEN

Line-structured light 3D measurement is often used for 3D contour reconstruction of objects in complex industrial environments, where light plane calibration is a key step. In this paper, we propose a calibration method for a line-structured optical system based on a hinge-connected double-checkerboards stereo target. First, the target is moved randomly in multiple positions at any angle within the camera measurement space. Then, by acquiring any one image of the target with line-structured light, the 3D coordinates of the light stripes feature points are solved with the help of the external parameter matrix of the target plane and the camera coordinate system. Finally, the coordinate point cloud is denoised and used to quadratically fit the light plane. Compared with the traditional line-structured measurement system, the proposed method can acquire two calibration images at once; thus, only one image of line-structured light is needed to complete the light plane calibration. There is no strict requirement for the target pinch angle and placement, which improve system calibration speed with high accuracy. The experimental results show that the maximum RMS error of this method is 0.075 mm, and the operation is simpler and more effective to meet the technical requirements of industrial 3D measurement.

14.
Chemosphere ; 327: 138484, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36963583

RESUMEN

Growing evidence indicates that short-term ozone (O3) exposure has substantial health consequences, but the relationship between short-term ambient O3 and insomnia, a common sleep disorder, is not clear. This study aimed to investigate the short-term effects of ambient O3 exposure on outpatient visits for adult insomnia and to explore the potential modifiers. A large-scale multihospital-based study was carried out in Chongqing, the largest city in Southwest China. Daily data on outpatient visits for adult insomnia, average concentrations of ambient air pollutants and meteorological factors were collected. We conducted quasi-Poisson regression with generalized additive model to assess the association between ambient O3 and outpatient visits for adult insomnia in varied windows of exposure. Subgroup analyses were applied to identify its modifiers. Totally, 140,159 adult insomnia outpatient visits were identified. The daily maximum 8-h average concentration of O3 was 69 µg/m3 during the study period, which greatly below the updated Chinese and WHO recommended limits (daily maximum 8-h average, O3: 100 µg/m3). Short-term O3 exposure was significantly negatively associated with outpatient visits for adult insomnia in different lag periods and the greatest decrease of outpatient visits for adult insomnia was found at lag 02 [0.93% (95% CI: 0.48%, 1.38%)]. Additionally, stronger links between O3 and adult insomnia outpatient visits were presented in cool seasons, and we did not observe any significant modified effects of gender and age. Moreover, the negative O3-insomnia association remained robust after controlling for other common air pollutants and comorbidities. In summary, short-term exposure to lower level of ambient O3, was associated with reduced daily outpatient visits for adult insomnia and such association showed to be more obvious in cool seasons.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Humanos , Ozono/análisis , Contaminación del Aire/análisis , Material Particulado/análisis , Pacientes Ambulatorios , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Contaminantes Atmosféricos/análisis , China/epidemiología
15.
Environ Res ; 222: 115400, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36736551

RESUMEN

As global climate change intensifies, people are paying increasing attention to the impact of temperature changes on adverse mental health outcomes, especially depression. While increasing attention has been paid to the effect of temperature, there is little research on the effect of humidity. We aimed to investigate the association between humidex, an index combining temperature and humidity to reflect perceived temperature, and outpatient visits for depression from 2014 to 2019 in Chongqing, the largest and one of the most hot and humid cities of China. We also aimed to further identify susceptible subgroups. A distributed lag non-linear model (DLNM) was used to explore the concentration-response relationship between humidex and depression outpatient visits. Hierarchical analysis was carried out by age and gender. A total of 155,436 visits for depression were collected from 2014 to 2019 (2191 days). We found that depression outpatient visits were significantly associated with extremely high humidex (≥40). The significant positive single-lag day effect existed at lag 0 (RR = 1.029, 95%CI: 1.000-1.059) to lag 2 (RR = 1.01, 95%CI: 1.004-1.028), and lag 12 (RR = 1.013, 95%CI: 1.002-1.024). The significant cumulative adverse effects lasted from lag 01 to lag 014. Hierarchical analyses showed that females and the elderly (≥60 years) appeared to be more susceptible to extremely high humidex. The attributable numbers (AN) and fraction (AF) of extremely high humidex on depression outpatients were 1709 and 1.10%, respectively. Extremely high humidex can potentially increase the risk of depression, especially in females and the elderly. More protective measures should be taken in vulnerable populations.


Asunto(s)
Depresión , Femenino , Humanos , Anciano , Factores de Tiempo , Temperatura , Humedad , China
16.
Food Chem Toxicol ; 174: 113663, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36775139

RESUMEN

T-2 toxin is a mycotoxin with multiple toxic effects and has emerged as an important food pollutant. Microglia play a significant role in the toxicity of various neurotoxins. However, whether they participate in the neurotoxicity of T-2 toxin has not been reported. To clarify this point, an in vivo mouse model of T-2 toxin (4 mg/kg) poisoning was established. The results of Morris water maze and open-field showed that T-2 toxin induced learning and memory impairment and locomotor inhibition. Meanwhile, T-2 toxin induced microglial activation, while inhibiting microglia activation by minocycline (50 mg/kg) suppressed the toxic effect of the T-2 toxin. To further unveil the potential mechanisms involved in T-2 toxin-induced microglial activation, an in vitro model of T-2 toxin (0, 2.5, 5, 10 ng/mL) poisoning was established using BV-2 cells. Transcriptomic sequencing revealed lots of differentially expressed genes related to MAPK/NF-κB pathway. Western blotting results further confirmed that T-2 toxin (5 ng/mL) induced the activation of MAPKs and their downstream NF-κB. Moreover, the addition of inhibitors of NF-κB and MAPKs reversed the microglial activation induced by T-2 toxin. Overall, microglial activation may contribute a considerable role in T-2 toxin-induced behavioral abnormalities, which could be MAPK/NF-κB pathway dependent.


Asunto(s)
FN-kappa B , Toxina T-2 , Ratones , Animales , FN-kappa B/metabolismo , Microglía , Toxina T-2/metabolismo , Transducción de Señal , Regulación de la Expresión Génica , Lipopolisacáridos/farmacología
17.
Clin Pharmacol Drug Dev ; 12(4): 436-446, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36626291

RESUMEN

A pharmacokinetic (PK) study and a bioequivalence (BE) study were conducted to investigate the PK characteristics and safety of lubiprostone in healthy Chinese subjects and to evaluate the BE between the test and the reference drugs. The PK study consisted of a fasting state cohort (a single dose of 24 µg of lubiprostone), a 2-period crossover fasting and fed state cohort (a single dose of 48 µg of lubiprostone), and a multiple-dose cohort (24 µg of lubiprostone twice daily). The BE study was a single-dose, 2-treatment, 4-period, replicated crossover study. The plasma concentration of 15-OH-lubiprostone (M3) was measured by high-performance liquid chromatography-tandem mass spectrometry. The PK parameters were calculated using the noncompartment model with Phoenix WinNonlin. After a single dose of 24 ug of lubiprostone, the main PK parameters of M3 were 49.2 pg/mL, 74.0 h/pg/mL, and 1.1 hours for maximum plasma concentration (Cmax ), area under the plasma concentration time curve from time 0 to the last time point, and t1/2 , respectively. The main PK parameters of M3 showed dose-proportional characteristics in the dose range of 24-48 µg. Food affects the PK parameters of M3. Compared to the fasting state, time to maximum plasma concentration was delayed, Cmax decreased slightly, while AUC increased significantly under the fed state. The test and reference products had similar PK parameters and were bioequivalent in the fed state.


Asunto(s)
Pueblos del Este de Asia , Humanos , Equivalencia Terapéutica , Lubiprostona , Estudios Cruzados , Área Bajo la Curva
18.
Rapid Commun Mass Spectrom ; 37(6): e9469, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36593223

RESUMEN

RATIONALE: Nasopharyngeal carcinoma (NPC) is a malignant tumor that is endemic in Southeast Asia, North Africa, and southern China. There is an urgent need for effective early diagnosis and treatment of this disease since NPC is currently often detected at advanced stages. METHODS: To reveal the underlying metabolic mechanisms and discover potential diagnostic biomarkers of NPC, we employed ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and UHPLC-Q-Exactive Orbitrap MS, respectively, to analyze 54 serum samples and 54 urine samples from 27 patients with NPC and 27 healthy control individuals. RESULTS: A total of 1230 metabolites were determined in serum samples, and 181 of the 1230 metabolites were significantly changed in NPC patients. The 181 metabolites were enriched in 16 pathways, including biosynthesis of unsaturated fatty acids, cholesterol metabolism, and ferroptosis. A total of 2509 metabolites were detected in the urine samples. Among them, 179 metabolites were significantly altered in NPC patients, and these metabolites were enriched in eight pathways, including the tricarboxylic acid (TCA) cycle and caffeine metabolism. Seven metabolites, including creatinine and paraxanthine, were found to be significantly changed in both NPC serum and urine samples. Based on them, further biomarker analysis revealed that the panel of three serum metabolites, octanoylcarnitine, creatinine, and decanoyl-l-carnitine, displayed a perfect diagnostic performance (area under the curve [AUC] = 0.973) to distinguish NPC patients from controls, while the other three-metabolite biomarker panel, consisting of stachydrine, decanoyl-l-carnitine, and paraxanthine, had an AUC = 0.809 to distinguish NPC and control in urine samples. CONCLUSION: This work highlights the key metabolites and metabolic pathways disturbed in NPC and presents potential biomarkers for effective diagnosis of this disease.


Asunto(s)
Metabolómica , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Creatinina , Cromatografía Líquida de Alta Presión/métodos , Metabolómica/métodos , Biomarcadores , Redes y Vías Metabólicas , Carnitina , Neoplasias Nasofaríngeas/diagnóstico
19.
Environ Sci Pollut Res Int ; 30(12): 35352-35365, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36534246

RESUMEN

Microglia-mediated neuroinflammation plays a vital role in the pathophysiological processes of multiple neurodegenerative diseases. Lipopolysaccharide (LPS) is an environmental poison that can induce inflammatory microglial activation. Matrix metalloproteinases (MMPs) are vital factors regulating microglial activation, and CD147 is a key MMP inducer, which can induce inflammation by inducing MMPs. However, whether it is involved in the regulation of microglial activation has not been reported. In this study, the role of CD147 in LPS-induced microglial inflammatory activation was investigated by establishing in vivo and in vitro models. The results suggested that LPS-induced microglial activation was accompanied by the induction of CD147 expression while the inhibition of CD147 expression could inhibit LPS-induced microglial inflammatory activation. In addition, the results also indicated that the role of CD147 in LPS-induced pro-inflammatory activation of microglia was related to its downstream MMP-3, MMP-8, and autophagy. Furthermore, the inhibition of MMP-3, MMP-8, and autophagy attenuated LPS-induced inflammatory activation of microglia. At the same time, there was a certain interaction between MMPs and autophagy, which is shown that inhibiting the expression of MMPs could inhibit autophagy, whereas inhibiting autophagy could inhibit the expression of MMPs. Taken together, we provided the first evidence that CD147/MMPs can be involved in LPS-induced inflammatory activation of microglia through an autophagy-dependent manner.


Asunto(s)
Lipopolisacáridos , Microglía , Humanos , Lipopolisacáridos/farmacología , Microglía/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo
20.
Sci Total Environ ; 860: 160438, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36435241

RESUMEN

BACKGROUND: Ambient air pollution has been linked to gestational complications. However, the evidence on the relationship between air pollution and fetal distress is limited. OBJECTIVES: To investigate the relationship between maternal short-term air pollution exposure and fetal distress, and to identify a potential susceptible population. METHODS: This matched case-control study, involving 313 pregnancy women with fetal distress was conducted in Xi'an, the largest city in Northwest China from 2013 to 2016. Each woman with fetal distress was randomly matched with four women without fetal distress of the same age, same gestational week, and registration in the same period (n = 1252). Inverse distance-weighted (IDW) interpolation was applied to estimate maternal air pollution exposure based on the residential addresses. We employed conditional logistic regression model to evaluate the relationship between air pollutants and fetal distress. Distributed lag nonlinear model (DLNM) was performed to examine the exposure-response relationship between air pollutants and fetal distress. RESULTS: Maternal short-term exposure to PM10, PM2.5-10 (PMc), SO2, NO2, and CO was associated with increased risk of fetal distress. Each 10 µg/m3 increment in PM10, PMc, SO2 at lag 014, and NO2 at lag 010, the odds ratio (ORs) of fetal distress were 1.027 (95 % confidence interval (CI): 1.004, 1.050), 1.058 (95 % CI: 1.014, 1.105), 1.140 (95 % CI: 1.029, 1.264), and 1.158 (95 % CI: 1.046, 1.283), respectively. Similarly, with a 0.1 mg/m3 increment in CO at lag 014, the OR of fetal distress was 1.029 (95 % CI: 1.002, 1.058). Stratified analyses showed that the estimate associations of PM10, PM2.5 and CO appeared to be stronger, although not statistically significantly, among women with gestational complications. CONCLUSION: Maternal short-term exposure to ambient air pollution may increase the risk of fetal distress. Understanding the detrimental role of air pollution in fetal distress can help us better develop preventative methods in reducing its' impact on maternal and fetal health.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Embarazo , Humanos , Femenino , Estudios de Casos y Controles , Dióxido de Nitrógeno , Sufrimiento Fetal/inducido químicamente , Exposición a Riesgos Ambientales , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Exposición Materna , China/epidemiología , Material Particulado/análisis
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