Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 275
Filtrar
2.
J Mech Behav Biomed Mater ; 155: 106553, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38640694

RESUMEN

Developing a gradient porous scaffold similar to bone structure is gaining increasing attention in bone tissue engineering. The GelMA/HAP hydrogel has demonstrated potential in bone repair. Although 3D printing can build GelMA/HAP with porous structure, fabricating porous GelMA/HAP with gradient porosity and pore size in one step remains challenging. In this paper, a gradient porous structure with controllable pore size, based on gelatin methacryloyl (GelMA) and hydxroxyapatite (HAP), was engineered and printed using stereolithography. Firstly, the GelMA and HAP were mixed to prepare a hydrogel with a solid content ranging from 10 wt% to 50 wt% for stereolithography. Taking advantage of the sol-gel characteristics of GelMA/HAP hydrogel, GelMA/HAP was fed on the workbench through a combination of extrusion and paving to form a thin layer. During the curing of each layer, the hydrogel exposed to the curing of a single UV beam immediately solidified, forming a highly interconnected porous structure. Additionally, the hydrogel outside the scanning range could be further polymerized to form a relatively dense structure due to the residual laser energy. Finally, without gradient structural design or changing printing parameters, the gradient porous structure of bone-like could be printed in a single-step process. By adjusting the curing parameters of the single UV beam and the concentration and size of ceramic in the hydrogel, the printed pore diameter of the spongy structure could be controlled within the range of 50-260 µm, while the thickness of the compact area could be adjusted within 130-670 µm.

3.
Huan Jing Ke Xue ; 45(5): 2596-2612, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629524

RESUMEN

PM2.5 remote sensing data was applied in this study, and Theil-Sen Median trend analysis and the Mann-Kendall significance test were utilized to analyze the temporal and spatial variation in PM2.5 in the Shandong Province from 2000 to 2021. The influencing power of the influencing factors on the spatial differentiation of PM2.5 concentration in the Shandong Province was detected at the provincial-city-county levels based on Geo-detector data. The results showed that:① on the temporal scale, the mean ρ(PM2.5)in the Shandong Province ranged from 38.15 to 88.63 µg·m-3 from 2000 to 2021, which was slightly higher than the secondary limit of inhalable particulate matter (35 µg·m-3) in the Ambient Air Quality Standards. On the interannual scale, 2013 was the peak year for the variation in ρ(PM2.5) with a value of 83.36 µg·m-3, according to which the trend of PM2.5 concentrations in the Shandong Province was divided into two phases:a continuous increase and a rapid decrease. On the seasonal scale, PM2.5 concentration presented the distribution characteristics of "low in summer and high in winter and moderate in spring and autumn" and the U-shaped change rule of first decreasing and then increasing. ② On the spatial scale, the PM2.5 concentration in the Shandong Province presented a spatial distribution pattern of "high in the west and low in the east." The areas with high PM2.5 concentration were distributed in the western area of the Shandong Province, whereas the areas with low PM2.5 concentration were distributed in the eastern peninsula region. The spatial variation in the changing trend of PM2.5 concentration showed significant spatial heterogeneity, and the extremely significant decrease was mainly distributed in the eastern peninsula region. ③ The results of factor detection showed that climate factor was an important factor affecting the spatial differentiation of PM2.5 concentration in the Shandong Province. Mean temperature had the highest influence on the spatial differentiation of PM2.5 concentration in the Shandong Province, with a q value of 0.512. Provincial-city-county multi-scale detection results showed that the influencing factors affecting the spatial differentiation of PM2.5 concentration and their influencing power differed at different spatial scales. At the provincial scale, mean temperature, sunshine duration, and slope were the main factors affecting the spatial differentiation of PM2.5 concentration. At the city level, precipitation, elevation, and relative humidity were the main factors affecting the spatial differentiation of PM2.5. At the county level, precipitation, mean temperature, and sunshine duration were the main factors affecting the spatial variation in PM2.5 concentration.

4.
Colloids Surf B Biointerfaces ; 238: 113873, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38552410

RESUMEN

In this study, the critical importance of designing an appropriate immobilized carrier and method for free lipase to ensure exceptional biological catalytic activity and stability was emphasized. Covalent organic frameworks (COF-1) were synthesized as a novel porous carrier with an azine structure (-CN-NC-) through the condensation of hydrazine hydrate and benzene-1,3,5-tricarbaldehyde at room temperature. Simultaneously, Rhizomucor miehei lipase (RML) was immobilized within the COF-1 carrier using an in-situ aqueous phase method. Characterization of the carrier and RML@COF-1 and evaluation of the lipase properties of RML and RML@COF-1 through p-Nitrophenyl palmitate hydrolysis were conducted. Additionally, application in the synthesis of 1, 3-dioleoyl-2-palmitoylglycerol (OPO) was explored. The results showed that RML@COF-1 exhibited a high enzymatic loading of 285.4 mg/g. Under 60℃ conditions, the activity of RML@COF-1 was 2.31 times higher than that of free RML, and RML@COF-1 retained 77.25% of its original activity after 10 cycles of repeated use, indicating its excellent thermal stability and repeatability. Under the optimal conditions (10%, 1:8 PPP/OA, 45℃, 5 h), the yield of OPO reached 47.35%, showcasing the promising application prospects of the novel immobilized enzyme synthesized via in-situ aqueous phase synthesis for OPO preparation.


Asunto(s)
Enzimas Inmovilizadas , Lipasa , Rhizomucor , Lipasa/metabolismo , Lipasa/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Rhizomucor/enzimología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Hidrólisis , Porosidad , Propiedades de Superficie , Triglicéridos/química , Triglicéridos/metabolismo
5.
J Anesth ; 38(3): 377-385, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38441686

RESUMEN

PURPOSE: More literature studies have reported that alfentanil is safe and effective for labor analgesia. However, there is no unified consensus on the optimal dosage of alfentanil used for epidural analgesia. This study explored the concentration at 90% of minimum effective concentration (EC90) of alfentanil combined with 0.075% ropivacaine in patients undergoing epidural labor analgesia to infer reasonable drug compatibility and provide guidance for clinical practice. METHODS: In this prospective, single-center, double-blind study, a total of 45 singleton term primiparas with vaginal delivery who volunteered for epidural labor analgesia were recruited. The first maternal was administered with 3 µg/mL alfentanil combined with 0.075% ropivacaine with the infusion of 10 mL of the mixture every 50 min at a background dose of 3 mL/h. In the absence of PCEA, a total of 15 mL of the mixture is injected per hour. The subsequent alfentanil concentration was determined on the block efficacy of the previous case, using an up-down sequential allocation with a bias-coin design. 30 min after epidural labor analgesia, the block of patient failed with visual analog score (VAS) > 3, the alfentanil concentration was increased in a 0.5 µg/mL gradient for the next patient, while the block was successful with VAS ≤ 3, the alfentanil concentration was remained or decreased in a gradient according to a randomized response list for the next patient. EC90 and 95% confidence interval were calculated by linear interpolation and prediction model with R statistical software. RESULTS: In this study, the estimated EC90 of alfentanil was 3.85 µg/mL (95% confidence interval, 3.64-4.28 µg/mL). CONCLUSION: When combined with ropivacaine 0.075%, the EC90 of alfentanil for epidural labor analgesia is 3.85 µg/mL in patients undergoing labor analgesia.


Asunto(s)
Alfentanilo , Analgesia Epidural , Analgesia Obstétrica , Analgésicos Opioides , Anestésicos Locales , Ropivacaína , Humanos , Ropivacaína/administración & dosificación , Femenino , Método Doble Ciego , Alfentanilo/administración & dosificación , Embarazo , Analgesia Epidural/métodos , Estudios Prospectivos , Adulto , Anestésicos Locales/administración & dosificación , Analgesia Obstétrica/métodos , Analgésicos Opioides/administración & dosificación , Relación Dosis-Respuesta a Droga , Dimensión del Dolor/métodos , Dimensión del Dolor/efectos de los fármacos
6.
J Appl Toxicol ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448046

RESUMEN

Fuzi, an effective common herb, is often combined with Gancao to treat disease in clinical practice with enhancing its efficacy and alleviating its toxicity. The major toxic and bioactive compounds in Fuzi and Gancao are aconitine (AC) and glycyrrhizic acid (GL), respectively. This study aims to elucidate detoxification mechanism between AC and GL from pharmacokinetic perspective using physiologically based pharmacokinetic (PBPK) model. In vitro experiments exhibited that AC was mainly metabolized by CYP3A1/2 in rat liver microsomes and transported by P-glycoprotein (P-gp) in Caco-2 cells. Kinetics assays showed that the Km and Vmax of AC towards CYP3A1/2 were 2.38 µM and 57.3 pmol/min/mg, respectively, whereas that of AC towards P-gp was 11.26 µM and 147.1 pmol/min/mg, respectively. GL markedly induced the mRNA expressions of CYP3A1/2 and MDR1a/b in rat primary hepatocytes. In vivo studies suggested that the intragastric and intravenous administration of GL significantly reduced systemic exposure of AC by 27% and 33%, respectively. Drug-drug interaction (DDI) model of PBPK predicted that co-administration of GL would decrease the exposure of AC by 39% and 45% in intragastric and intravenous dosing group, respectively. The consistency between predicted data and observed data confirmed that the upregulation of CYP3A1/2 and P-gp was the crucial detoxification mechanism between AC and GL. Thus, this study provides a demonstration for elucidating the compatibility mechanisms of herbal formula using PBPK modeling and gives support for the clinical co-medication of Fuzi and Gancao.

7.
Neurol Sci ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488928

RESUMEN

BACKGROUND: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. METHODS: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. RESULTS: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. CONCLUSION: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy.

8.
J Bioenerg Biomembr ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427129

RESUMEN

Tetramethylpyrazine (TMP) is one of the active ingredients of Chuan Xiong that has been reported to have effects on numerous diseases, including diabetic nephropathy (DN). Whereas, related molecular mechanisms are not fully elucidated. We aimed to explore circACTR2's role in TMP-mediated protective effects on DN. In vitro DN condition was established in human kidney cells (HK-2) by treating high glucose (HG). CCK-8 assay and flow cytometry assay were used to observe cell viability and survival. Oxidative stress was determined by the associated markers using kits. The release of inflammatory factors was detected using ELISA kits. Quantitative real-time PCR (qPCR) and western blot were utilized for expression analysis of cricACTR2, miR-140-5p, and GLI pathogenesis-related 2 (GLIPR2). The binding between miR-140-5p and circACTR2 or GLIPR2 was confirmed by dual-luciferase, RIP, and pull-down studies. HG largely induced HK-2 cell apoptosis, oxidative stress, and inflammation, which were alleviated by TMP. CircACTR2's expression was enhanced in HG-treated HK-2 cells but attenuated in HG + TMP-treated HK-2 cells. CircACTR2 overexpression attenuated the functional effects of TMP and thus restored HG-induced cell apoptosis, oxidative stress, and inflammation. CircACTR2 bound to miR-140-5p to enhance the expression of GLIPR2. MiR-140-5p restoration or GLIPR2 inhibition reversed the role of circACTR2 overexpression. CircACTR2 attenuated the protective effects of TMP on HG-induced HK-2 cell damages by regulating the miR-140-5p/GLIPR2 network, indicating that circACTR2 was involved in the functional network of TMP in DN.

9.
Huan Jing Ke Xue ; 45(3): 1615-1628, 2024 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-38471874

RESUMEN

Quantitatively determining the direct, indirect, and comprehensive effects of climatic factors on the growing season of the vegetation GPP (GPPGS) in the middle and lower reaches of the Yangtze River at the regional and vegetation type scales can provide a scientific basis for the management and restoration of regional vegetation resources under the background of global climate change. Using MODIS GPP data, meteorological data, and vegetation type data, combined with Theil-Sen Median trend analysis and the Mann-Kendall significance test, the spatiotemporal characteristics of the GPPGS in the middle and lower reaches of the Yangtze River were investigated at different temporal and spatial scales. Path analysis was used to further reveal the direct, indirect, and comprehensive effects of climate factors on GPPGS variation in different vegetation types. The results showed that:① from 2000 to 2021, the vegetation GPPGS in the middle and lower reaches of the Yangtze River showed a fluctuating upward trend, with a rising rate (in terms of C, same below) of 2.70 g·(m2·a)-1 (P<0.01). The GPPGS of different vegetation types all showed a significant upward trend (P<0.01), with shrubs having the highest upward rate of 3.31 g·(m2·a)-1 and cultivated vegetation having the lowest upward rate of 2.54 g·(m2·a)-1. ② The proportion of the area with an upward trend in GPPGS in the middle and lower reaches of the Yangtze River was 88.11%. The proportion of the area with an upward trend in GPPGS was greater than 84% for all different vegetation types, with shrubs (49.76%) and cultivated vegetation (44.36%) having significantly higher proportions of the area with an upward trend than that in other vegetation types. ③ The path analysis results showed that precipitation and the maximum temperature had a significant positive direct effect on vegetation GPPGS (P<0.05), whereas solar radiation had a non-significant positive effect (P ≥ 0.05). The indirect effects of maximum temperature, precipitation, and solar radiation on vegetation GPPGS were all non-significantly negative (P ≥ 0.05). Under the combined effects of direct and indirect influences, precipitation and maximum temperature had a non-significant positive effect on vegetation GPPGS (P ≥ 0.05), whereas solar radiation had a non-significant negative effect on vegetation GPPGS (P ≥ 0.05). Among different vegetation types, precipitation was the main climate factor affecting the changes in GPPGS of cultivated vegetation, whereas the maximum temperature was the main climate factor affecting the changes in GPPGS of coniferous forests, broad-leaved forests, shrubs, and grasslands. ④ The changes in vegetation GPPGS in the middle and lower reaches of the Yangtze River were mainly influenced by the direct effects of maximum temperature, precipitation, and solar radiation, with the direct effect of precipitation dominating 56.72% of the changes in GPPGS. The research results can provide a reference for quantifying the carbon sequestration potential of vegetation in the middle and lower reaches of the Yangtze River and formulating ecological restoration governance policies tailored to local conditions under the background of global climate change.


Asunto(s)
Cambio Climático , Ecosistema , Ríos , Estaciones del Año , Bosques , Temperatura , China
10.
Mol Biotechnol ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429624

RESUMEN

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8.

11.
Int J Oral Sci ; 16(1): 21, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424060

RESUMEN

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.


Asunto(s)
Ameloblastoma , Humanos , Ameloblastoma/genética , Ameloblastoma/patología , Recurrencia Local de Neoplasia , Fenotipo , Transformación Celular Neoplásica , Perfilación de la Expresión Génica
12.
Artículo en Inglés | MEDLINE | ID: mdl-38319760

RESUMEN

Unsupervised graph-structure learning (GSL) which aims to learn an effective graph structure applied to arbitrary downstream tasks by data itself without any labels' guidance, has recently received increasing attention in various real applications. Although several existing unsupervised GSL has achieved superior performance in different graph analytical tasks, how to utilize the popular graph masked autoencoder to sufficiently acquire effective supervision information from the data itself for improving the effectiveness of learned graph structure has been not effectively explored so far. To tackle the above issue, we present a multilevel contrastive graph masked autoencoder (MCGMAE) for unsupervised GSL. Specifically, we first introduce a graph masked autoencoder with the dual feature masking strategy to reconstruct the same input graph-structured data under the original structure generated by the data itself and learned graph-structure scenarios, respectively. And then, the inter-and intra-class contrastive loss is introduced to maximize the mutual information in feature and graph-structure reconstruction levels simultaneously. More importantly, the above inter-and intra-class contrastive loss is also applied to the graph encoder module for further strengthening their agreement at the feature-encoder level. In comparison to the existing unsupervised GSL, our proposed MCGMAE can effectively improve the training robustness of the unsupervised GSL via different-level supervision information from the data itself. Extensive experiments on three graph analytical tasks and eight datasets validate the effectiveness of the proposed MCGMAE.

13.
Heliyon ; 10(4): e26023, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38390045

RESUMEN

The augmented prevalence of Se (Se) pollution can be attributed to various human activities, such as mining, coal combustion, oil extraction and refining, and agricultural irrigation. Although Se is vital for animals, humans, and microorganisms, excessive concentrations of this element can give rise to potential hazards. Consequently, numerous approaches have been devised to mitigate Se pollution, encompassing physicochemical techniques and bioremediation. The recognition of Se volatilization as a potential strategy for mitigating Se pollution in contaminated environments is underscored in this review. This study delves into the volatilization mechanisms in various organisms, including plants, microalgae, and microorganisms. By assessing the efficacy of Se removal and identifying the rate-limiting steps associated with volatilization, this paper provides insightful recommendations for Se mitigation. Constructed wetlands are a cost-effective and environmentally friendly alternative in the treatment of Se volatilization. The fate, behavior, bioavailability, and toxicity of Se within complex environmental systems are comprehensively reviewed. This knowledge forms the basis for developing management plans that aimed at mitigating Se contamination in wetlands and protecting the associated ecosystems.

14.
World J Pediatr Surg ; 7(1): e000641, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38374897

RESUMEN

Objective: The study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus, while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation. The former has a higher risk of seizure recurrence. Methods: We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery. To identify the risk factors for seizure recurrence, we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses. AED tapering was standardized, involving a 25% reduction in the dose of a single type of AED every 2 weeks, independent of the presurgical AED load. Results: We attempted AED withdrawal in 116 (63.7%) children. Twenty-eight (24.1%) children experienced seizure recurrence during or after AED withdrawal. A greater number of AEDs used at the time of surgery (p=0.005), incomplete resection (p=0.001), and presence of IED on postoperative EEG (p=0.011) are predictors of seizure recurrence. The completeness of resection and seizure recurrence after AED withdrawal were related to the presence of IED on the EEG, but not to the concordance of IED with surgical sites. Conclusion: For children with abnormal EEG, the decision to discontinue AED should be made more cautiously, regardless of the relative location of the discharge site and the surgical site.

15.
J Ethnopharmacol ; 326: 117909, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38350503

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Gancao Decoction (GCD) is widely used to treat cholestatic liver injury. However, it is unclear whether is related to prevent hepatocellular necroptosis. AIM OF THE STUDY: The purpose of this study is to clarify the therapeutic effects of GCD against hepatocellular necroptosis induced by cholestasis and its active components. MATERIALS AND METHODS: We induced cholestasis model in wild type mice by ligating the bile ducts or in Nlrp3-/- mice by intragastrical administering Alpha-naphthylisothiocyanate (ANIT). Serum biochemical indices, liver pathological changes and hepatic bile acids (BAs) were measured to evaluate GCD's hepatoprotective effects. Necroptosis was assessed by expression of hallmarkers in mice liver. Moreover, the potential anti-necroptotic effect of components from GCD were investigated and confirmed in ANIT-induced cholestasis mice and in primary hepatocytes from WT mouse stimulated with Tumor Necrosis Factor alpha (TNF-α) and cycloheximide (CHX). RESULTS: GCD dose-dependently alleviated hepatic necrosis, reduced serum aminotranferase activity in both BDL and ANIT-induced cholestasis models. More importantly, the expression of hallmarkers of necroptosis, including MLKL, RIPK1 and RIPK3 phosphorylation (p- MLKL, p-RIPK1, p-RIPK3) were reduced upon GCD treatment. Glycyrrhetinic acid (GA), the main bioactive metabolite of GCD, effectively protected against ANIT-induced cholestasis, with decreased expression of p-MLKL, p-RIPK1 and p-RIPK3. Meanwhile, the expression of Fas-associated death domain protein (FADD), long isoform of cellular FLICE-like inhibitory protein (cFLIPL) and cleaved caspase 8 were upregulated upon GA treatment. Moreover, GA significantly increased the expression of active caspase 8, and reduced that of p-MLKL in TNF-α/CHX induced hepatocytes necroptosis. CONCLUSIONS: GCD substantially inhibits necroptosis in cholestatic liver injury. GA is the main bioactive component responsible for the anti-necroptotic effects, which correlates with upregulation of c-FLIPL and active caspase 8.


Asunto(s)
Colestasis , Medicamentos Herbarios Chinos , Ácido Glicirretínico , Glycyrrhiza , Ratones , Animales , Factor de Necrosis Tumoral alfa/farmacología , Caspasa 8 , Necroptosis , Hígado , Colestasis/inducido químicamente , Colestasis/tratamiento farmacológico , Colestasis/patología , Ácido Glicirretínico/farmacología , 1-Naftilisotiocianato/toxicidad
16.
Cell ; 187(6): 1387-1401.e13, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38412859

RESUMEN

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.


Asunto(s)
Proteínas del Tejido Nervioso , Degeneración Retiniana , Animales , Ratones , Traslocación Bacteriana , Proteínas del Ojo/genética , Amaurosis Congénita de Leber/genética , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Retina/metabolismo , Degeneración Retiniana/genética , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología
17.
Epilepsy Behav ; 151: 109645, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244419

RESUMEN

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.


Asunto(s)
Epilepsia , Humanos , Epilepsia/terapia , Convulsiones , Certificación , China , Lenguaje
19.
Environ Int ; 183: 108430, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38219544

RESUMEN

Land use regression (LUR) models are widely used in epidemiological and environmental studies to estimate humans' exposure to air pollution within urban areas. However, the early models, developed using linear regressions and data from fixed monitoring stations and passive sampling, were primarily designed to model traditional and criteria air pollutants and had limitations in capturing high-resolution spatiotemporal variations of air pollution. Over the past decade, there has been a notable development of multi-source observations from low-cost monitors, mobile monitoring, and satellites, in conjunction with the integration of advanced statistical methods and spatially and temporally dynamic predictors, which have facilitated significant expansion and advancement of LUR approaches. This paper reviews and synthesizes the recent advances in LUR approaches from the perspectives of the changes in air quality data acquisition, novel predictor variables, advances in model-developing approaches, improvements in validation methods, model transferability, and modeling software as reported in 155 LUR studies published between 2011 and 2023. We demonstrate that these developments have enabled LUR models to be developed for larger study areas and encompass a wider range of criteria and unregulated air pollutants. LUR models in the conventional spatial structure have been complemented by more complex spatiotemporal structures. Compared with linear models, advanced statistical methods yield better predictions when handling data with complex relationships and interactions. Finally, this study explores new developments, identifies potential pathways for further breakthroughs in LUR methodologies, and proposes future research directions. In this context, LUR approaches have the potential to make a significant contribution to future efforts to model the patterns of long- and short-term exposure of urban populations to air pollution.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Material Particulado/análisis , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Modelos Lineales , Dióxido de Nitrógeno/análisis
20.
Biosens Bioelectron ; 250: 116056, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38271889

RESUMEN

Green tea is popular among consumers because of its high nutritional value and unique flavor. There is often a strong correlation among the type of tea, its quality level and the price. Therefore, the rapid identification of tea types and the judgment of tea quality grades are particularly important. In this work, a novel sensor array based on nanozyme with polyphenol oxidase (PPO) activity is proposed for the identification of tea polyphenols (TPs) and Chinese green tea. The absorption spectra changes of the nanozyme and its substrate in the presence of different TPs were first investigated. The feature spectra were scientifically selected using genetic algorithm (GA), and then a sensor array with 15 sensing units (5 wavelengths × 3 time) was constructed. Combined with the support vector machine (SVM) discriminative model, the discriminative rate of this sensor array was 100% for different concentrations of typical TPs in Chinese green tea with a detection limit of 5 µM. In addition, the identification of different concentrations of the same tea polyphenols and mixed tea polyphenols have also been achieved. Based on the above study, we further developed a facile and efficient new method for the category differentiation and adulteration identification of green tea, and the accuracy of this array was 96.88% and 100% for eight types of green teas and different adulteration ratios of Biluochun, respectively. This work has significance for the rapid discrimination of green tea brands and adulteration.


Asunto(s)
Técnicas Biosensibles , Camellia sinensis , , Polifenoles , Catecol Oxidasa , China
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...